1  1292 139 DECREASED BLOOD PRESSURE IS RELATED TO CHANGES IN NF-KB PROMOTER METHYLATION LEVELS AFTER BARIATRIC SURGERY. BACKGROUND: OBESITY IS CHARACTERIZED BY A CHRONIC, LOW-GRADE INFLAMMATION, AND BARIATRIC SURGERY IS PROPOSED AS AN EFFECTIVE TREATMENT FOR REDUCING THE OBESITY-RELATED CO-MORBIDITIES. EPIGENETIC MODIFICATIONS COULD BE INVOLVED IN THE METABOLIC IMPROVEMENT AFTER SURGERY. OBJECTIVE: THE MAIN AIM OF THIS STUDY WAS TO EVALUATE WHETHER DNA METHYLATION PATTERN FROM GENES RELATED TO INFLAMMATION AND INSULIN RESPONSE IS ASSOCIATED WITH THE METABOLIC IMPROVEMENT AFTER BARIATRIC SURGERY IN MORBIDLY OBESE PATIENTS AND IF THESE CHANGES DEPEND ON THE SURGICAL PROCEDURE. SETTING: UNIVERSITY HOSPITAL, SPAIN. METHODS: WE STUDIED 60 SEVERELY OBESE PATIENTS; 31 UNDERWENT ROUX-EN-Y GASTRIC BYPASS AND 29 UNDERWENT LAPAROSCOPIC SLEEVE GASTRECTOMY. ALL PATIENTS WERE EXAMINED BEFORE AND AT 6 MONTHS AFTER BARIATRIC SURGERY. DNA METHYLATION PROFILE OF GENES RELATED TO THE INFLAMMATORY RESPONSE AND INSULIN SENSITIVITY WAS MEASURED BY PYROSEQUENCING. RESULTS: THE PROMOTER METHYLATION LEVELS OF THE NFKB1 GENE WERE INCREASED SIGNIFICANTLY AFTER SURGERY (2.16 +/- .9 VERSUS 2.8 +/- 1.03). THE DECREASE IN BLOOD PRESSURE, BOTH SYSTOLIC AND DIASTOLIC, AFTER SURGERY WAS SIGNIFICANTLY ASSOCIATED WITH THE CHANGES IN THE PROMOTER METHYLATION LEVELS OF THE NFKB1 GENE (BETA = -.513, P = .003 AND BETA = -.543, P = .004, RESPECTIVELY). A DECREASE IN INFLAMMATION STATUS, MEASURED BY HIGH SENSITIVITY C-REACTIVE PROTEIN VALUES, WAS ASSOCIATED WITH CHANGES IN SLC19A1 METHYLATION LEVELS. CONCLUSION: OUR STUDY SHOWS FOR THE FIRST TIME AN ASSOCIATION BETWEEN NFKB1 METHYLATION LEVELS AND BLOOD PRESSURE AFTER BARIATRIC SURGERY, HIGHLIGHTING THE POSSIBLE FUNCTION OF THIS GENE IN THE REGULATION OF ARTERIAL PRESSURE. REGARDING SLC19A1, THIS GENE COULD POSITION AS A POTENTIAL TARGET LINKING INFLAMMATION AND INSULIN RESISTANCE.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
2   561  52 BARIATRIC SURGERY-INDUCED WEIGHT LOSS AND ASSOCIATED GENOME-WIDE DNA-METHYLATION ALTERATIONS IN OBESE INDIVIDUALS. BACKGROUND: OBESITY IS A MULTIFACTORIAL AND CHRONIC CONDITION OF GROWING UNIVERSAL CONCERN. IT HAS RECENTLY BEEN REPORTED THAT BARIATRIC SURGERY IS A MORE SUCCESSFUL TREATMENT FOR SEVERE OBESITY THAN OTHER NONINVASIVE INTERVENTIONS, RESULTING IN RAPID SIGNIFICANT WEIGHT LOSS AND ASSOCIATED CHRONIC DISEASE REMISSION. THE IDENTIFICATION OF DISTINCT EPIGENETIC PATTERNS IN PATIENTS WHO ARE OBESE OR HAVE METABOLIC IMBALANCES HAS SUGGESTED A POTENTIAL ROLE FOR EPIGENETIC ALTERATIONS IN CAUSAL OR MEDIATING PATHWAYS IN THE DEVELOPMENT OF OBESITY-RELATED PATHOLOGIES. SPECIFIC CHANGES IN THE EPIGENOME (DNA METHYLOME), ASSOCIATED WITH METABOLIC DISORDERS, CAN BE DETECTED IN THE BLOOD. WE INVESTIGATED WHETHER SUCH EPIGENETIC CHANGES ARE REVERSIBLE AFTER WEIGHT LOSS USING GENOME-WIDE DNA METHYLOME ANALYSIS OF BLOOD SAMPLES FROM INDIVIDUALS WITH SEVERE OBESITY (MEAN BMI ~ 45) UNDERGOING BARIATRIC SURGERY. RESULTS: OUR ANALYSIS REVEALED 41 SIGNIFICANT (BONFERRONI P < 0.05) AND 1169 (FALSE DISCOVERY RATE P < 0.05) SUGGESTIVE DIFFERENTIALLY METHYLATED POSITIONS (DMPS) ASSOCIATED WITH WEIGHT LOSS DUE TO BARIATRIC SURGERY. AMONG THE 41 SIGNIFICANT DMPS, 5 CPGS WERE REPLICATED IN AN INDEPENDENT COHORT OF BMI-DISCORDANT MONOZYGOTIC TWINS (THE HEAVIER TWIN UNDERWENT DIET-INDUCED WEIGHT LOSS). THE EFFECT SIZES OF THESE 5 CPGS WERE CONSISTENT ACROSS DISCOVERY AND REPLICATION SETS (P < 0.05). WE ALSO IDENTIFIED 192 DIFFERENTIALLY METHYLATED REGIONS (DMRS) AMONG WHICH SMAD6 AND PFKFB3 GENES WERE THE TOP HYPERMETHYLATED AND HYPOMETHYLATED REGIONS, RESPECTIVELY. PATHWAY ENRICHMENT ANALYSIS OF THE DMR-ASSOCIATED GENES SHOWED THAT FUNCTIONAL PATHWAYS RELATED TO IMMUNE FUNCTION AND TYPE 1 DIABETES WERE SIGNIFICANT. WEIGHT LOSS DUE TO BARIATRIC SURGERY ALSO SIGNIFICANTLY DECELERATED EPIGENETIC AGE 12 MONTHS AFTER THE INTERVENTION (MEAN = - 4.29; P = 0.02). CONCLUSIONS: WE IDENTIFIED WEIGHT LOSS-ASSOCIATED DNA-METHYLATION ALTERATIONS TARGETING IMMUNE AND INFLAMMATORY GENE PATHWAYS IN BLOOD SAMPLES FROM BARIATRIC-SURGERY PATIENTS. THE TOP HITS WERE REPLICATED IN SAMPLES FROM AN INDEPENDENT COHORT OF BMI-DISCORDANT MONOZYGOTIC TWINS FOLLOWING A HYPOCALORIC DIET. ENERGY RESTRICTION AND BARIATRIC SURGERY THUS SHARE CPGS THAT MAY REPRESENT EARLY INDICATORS OF RESPONSE TO THE METABOLIC EFFECTS OF WEIGHT LOSS. THE ANALYSIS OF BARIATRIC SURGERY-ASSOCIATED DMRS SUGGESTS THAT EPIGENETIC REGULATION OF GENES INVOLVED IN ENDOTHELIAL AND ADIPOSE TISSUE FUNCTION IS KEY IN THE PATHOPHYSIOLOGY OF OBESITY.	2022	

3  4066  41 MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION AS AN INDICATOR OF OFFSPRING METABOLIC SYNDROME RISK IN LATER LIFE THROUGH EPIGENETIC IMPRINTING: A SYSTEMATIC REVIEW. AIMS: THIS REVIEW EXAMINED WHETHER MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION EFFECTS AN OFFSPRING'S LIKELIHOOD OF DEVELOPING CHRONIC METABOLIC RELATED CONDITIONS DUE TO EPIGENETIC IMPRINTING. METHODS: A LITERATURE SEARCH WAS CONDUCTED IN MULTIPLE SCIENCE DATABASES AND LIMITED TO STUDIES PUBLISHED AFTER 2012, IN ENGLISH LANGUAGE AND PEER REVIEWED. THE DATA FROM SELECTED ARTICLES WERE EXTRACTED AND A QUALITATIVE APPROACH WAS EMPLOYED DUE TO HETEROGENEITY OF RESULTS. RESULTS: NEWBORNS FROM OBESE FATHERS SHOWED ALTERED METHYLATION OVERALL AND SIGNIFICANT HYPOMETHYLATION AT THE INSULIN-LIKE GROWTH FACTOR 2 (IGF2) GENE. HIGH MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) WAS ASSOCIATED WITH ALTERED OFFSPRING DNA METHYLATION LEVELS AND GESTATIONAL DIABETES MELLITUS INDUCED SIGNIFICANTLY INCREASED METHYLATION LEVELS IN OFFSPRING. GESTATIONAL WEIGHT GAIN WAS NOT ASSOCIATED WITH DIFFERENTIALLY METHYLATED CORD BLOOD. BIRTH WEIGHT WAS HIGHER IN OFFSPRING EXPOSED TO FAMINE IN EARLY GESTATION. OFFSPRING BORN POST MATERNAL BARIATRIC SURGERY SHOWED A LOWER PERCENTAGE OF BODY FAT AND IMPROVED FASTING INSULIN LEVELS COMPARED TO SIBLINGS BORN PRE-MATERNAL BARIATRIC SURGERY. CONCLUSIONS: THE AVAILABLE EVIDENCE SUGGESTS THAT POOR MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION CAN INCREASE THE RISK OF METABOLIC SYNDROME IN OFFSPRING, THROUGH EPIGENETIC IMPRINTING. POTENTIAL PARENTS SHOULD BE ADVISED THAT MAINTAINING A HEALTHY DIET AND BMI IS LIKELY TO REDUCE THE RISK OF METABOLIC SYNDROME IN OFFSPRING.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
4  1098  32 COLLATERAL DAMAGE: MATERNAL OBESITY DURING PREGNANCY CONTINUES TO RISE. IMPORTANCE: THE PANDEMIC OF OBESITY DURING PREGNANCY NOW AFFLICTS 1 OUT OF EVERY 2 PREGNANT WOMEN IN THE UNITED STATES. EVEN THOUGH UNINTENDED PREGNANCY HAS DECREASED TO 45% OF ALL PREGNANCIES, 50% OF THOSE UNINTENDED PREGNANCIES OCCUR IN OBESE WOMEN. OBJECTIVE: THIS STUDY AIMS TO IDENTIFY WHY CURRENT LIFESTYLE INTERVENTIONS FOR OBESE PREGNANCY ARE NOT EFFECTIVE AND WHAT THE NEWER COMPLICATIONS ARE FOR OBESITY DURING PREGNANCY. EVIDENCE ACQUISITION: AVAILABLE LITERATURES ON CURRENT TREATMENTS FOR MATERNAL OBESITY WERE REVIEWED FOR EFFECTIVENESS. EMERGING MATERNAL AND INFANT COMPLICATIONS FROM OBESITY DURING PREGNANCY WERE EXAMINED FOR SIGNIFICANCE. RESULTS: LIMITATIONS IN SUCCESSFUL INTERVENTIONS FELL INTO 3 BASIC CATEGORIES TO INCLUDE THE FOLLOWING: (1) PRECONCEPTION WEIGHT LOSS; (2) BARIATRIC SURGERY BEFORE PREGNANCY; AND (3) PREVENTION OF EXCESSIVE GESTATIONAL WEIGHT GAIN DURING PREGNANCY. EMERGING SIGNIFICANT PHYSIOLOGICAL CHANGES FROM MATERNAL OBESITY IS COMPOSED OF INFLAMMATION (PLACENTA AND HUMAN MILK), METABOLISM (HORMONES, MICROBIOME, FATTY ACIDS), AND OFFSPRING OUTCOMES (BODY COMPOSITION, CONGENITAL MALFORMATIONS, CHRONIC KIDNEY DISEASE, ASTHMA, NEURODEVELOPMENT, AND BEHAVIOR). CONCLUSIONS AND RELEVANCE: ARE CURRENT PREPREGNANCY LIFESTYLE AND BEHAVIORAL INTERVENTIONS FEASIBLE TO PREVENT MATERNAL OBESITY COMPLICATIONS? EPIGENETIC AND METABOLOMIC RESEARCH WILL BE CRITICAL TO DETERMINE WHAT IS NEEDED TO BLUNT THE EFFECTS OF MATERNAL OBESITY AND TO DISCOVER SUCCESSFUL TREATMENT.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
5  6469  49 TISSUE-SPECIFIC METHYLATION PROFILE IN OBESE PATIENTS WITH TYPE 2 DIABETES BEFORE AND AFTER ROUX-EN-Y GASTRIC BYPASS. EATING HABITS, LIFESTYLES, AND EXPOSURE TO SPECIFIC ENVIRONMENTAL FACTORS CAN GREATLY IMPACT THE RISK OF DEVELOPING TYPE 2 DIABETES (T2D), INFLUENCE THE GENOME EPIGENETICALLY, AND AFFECT THE EXPRESSION OF GENES, INCLUDING GENES RELATED TO GLYCEMIC CONTROL, AT ANY STAGE OF LIFE. THE EPIGENETIC MECHANISM UNDERLYING OBESITY AND T2D PATHOGENESIS REMAINS POORLY UNDERSTOOD. CONVENTIONAL STRATEGIES FOR THE TREATMENT OF OBESITY AND ITS COMORBIDITIES OFTEN HAVE POOR LONG-TERM ADHERENCE, AND PHARMACOLOGICAL INTERVENTIONS ARE LIMITED. BARIATRIC SURGERY IS THE MOST EFFECTIVE CURRENT OPTION TO TREAT SEVERE OBESITY, AND ROUX-EN-Y GASTRIC BYPASS (RYGB) IS THE MOST APPLIED TECHNIQUE WORLDWIDE. EPIGENETIC CHANGES DIFFER DEPENDING ON THE APPROACH USED TO TREAT OBESITY AND ITS ASSOCIATED COMORBIDITIES (CLINICAL OR SURGICAL). COMPARED TO PRIMARY CLINICAL CARE, BARIATRIC SURGERY LEADS TO MUCH GREATER LOSS OF BODY WEIGHT AND HIGHER REMISSION RATES OF T2D AND METABOLIC SYNDROME, WITH METHYLATION PROFILES IN PROMOTER REGIONS OF GENES IN OBESE INDIVIDUALS BECOMING SIMILAR TO THOSE OF NORMAL-WEIGHT INDIVIDUALS. BARIATRIC SURGERY CAN INFLUENCE DNA METHYLATION IN PARALLEL WITH CHANGES IN GENE EXPRESSION PATTERN. CHANGES IN CLINICAL BIOMARKERS THAT REFLECT IMPROVEMENTS IN GLUCOSE AND LIPID METABOLISM AFTER RYGB OFTEN OCCUR BEFORE MAJOR WEIGHT LOSS AND ARE COORDINATED BY SURGERY-INDUCED CHANGES IN INTESTINAL HORMONES. THEREFORE, THE INTESTINE METHYLATION PROFILE WOULD ASSIST IN UNDERSTANDING THE MECHANISMS INVOLVED IN IMPROVED GLYCEMIC CONTROL AFTER BARIATRIC SURGERY. THE MAIN OBJECTIVES IN THIS AREA FOR THE FUTURE ARE TO IDENTIFY EPIGENETIC MARKS THAT COULD BE USED AS EARLY INDICATORS OF METABOLIC RISK, AND TO DEVELOP TREATMENTS ABLE TO DELAY OR EVEN REVERSE THESE EPIGENETIC CHANGES. STUDIES THAT PROVIDE THE "HUMAN EPIGENETIC PROFILE" WILL BE OF CONSIDERABLE VALUE TO IDENTIFY TISSUE-SPECIFIC EPIGENETIC SIGNATURES AND THEIR ROLE IN THE DEVELOPMENT OF CHRONIC DISEASES. FURTHER STUDIES SHOULD APPLY METHODS BASED ON GLOBAL ANALYSIS OF THE GENOME TO IDENTIFY METHYLATED SITES ASSOCIATED WITH DISEASE AND EPIGENETIC MARKS ASSOCIATED WITH THE REMODELING RESPONSE TO BARIATRIC SURGERY. THIS REVIEW DESCRIBES THE MAIN EPIGENETIC ALTERATIONS ASSOCIATED WITH OBESITY AND T2D AND THE POTENTIAL ROLE OF RYGB IN REMODELING THESE CHANGES.	2017	
                                                                                                                                                                       
6  6462  44 TISSUE AND CIRCULATING MICRORNAS AS BIOMARKERS OF RESPONSE TO OBESITY TREATMENT STRATEGIES. BACKGROUND: OBESITY, CHARACTERIZED BY AN INCREASED AMOUNT OF ADIPOSE TISSUE, IS A METABOLIC CHRONIC ALTERATION WHICH HAS REACHED PANDEMIC PROPORTION. LIFESTYLE CHANGES ARE THE FIRST LINE THERAPY FOR OBESITY AND A LARGE VARIETY OF DIETARY APPROACHES HAVE DEMONSTRATED EFFICACY IN PROMOTING WEIGHT LOSS AND IMPROVING OBESITY-RELATED METABOLIC ALTERATIONS. BESIDES DIET AND PHYSICAL ACTIVITY, BARIATRIC SURGERY MIGHT BE AN EFFECTIVE THERAPEUTIC STRATEGY FOR MORBID OBESE PATIENTS. RESPONSE TO WEIGHT-LOSS INTERVENTIONS IS CHARACTERISED BY HIGH INTER-INDIVIDUAL VARIABILITY, WHICH MIGHT INVOLVE EPIGENETIC FACTORS. MICRORNAS HAVE CRITICAL ROLES IN METABOLIC PROCESSES AND THEIR DYSREGULATED EXPRESSION HAS BEEN REPORTED IN OBESITY. AIM: THE AIM OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF CURRENT STUDIES EVALUATING CHANGES IN MICRORNA EXPRESSION IN OBESE PATIENTS UNDERGOING LIFESTYLE INTERVENTIONS OR BARIATRIC SURGERY. RESULTS: A CONSIDERABLE NUMBER OF STUDIES HAVE REPORTED A DIFFERENTIAL EXPRESSION OF CIRCULATING MICRORNAS BEFORE AND AFTER VARIOUS DIETARY AND BARIATRIC SURGERY APPROACHES, IDENTIFYING SEVERAL CANDIDATE BIOMARKERS OF RESPONSE TO WEIGHT LOSS. SIGNIFICANT CHANGES IN MICRORNA EXPRESSION HAVE BEEN OBSERVED AT A TISSUE LEVEL AS WELL, WITH ENTIRELY DIFFERENT PATTERNS BETWEEN VISCERAL AND SUBCUTANEOUS ADIPOSE TISSUE. INTERESTINGLY, RELEVANT DIFFERENCES IN MICRORNA EXPRESSION HAVE EMERGED BETWEEN RESPONDERS AND NON-RESPONDERS TO DIETARY OR SURGICAL INTERVENTIONS. A WIDE VARIETY OF DYSREGULATED MICRORNA TARGET PATHWAYS HAVE ALSO BEEN IDENTIFIED, HELPING TO UNDERSTAND THE PATHOPHYSIOLOGICAL MECHANISMS UNDERLYING OBESITY AND OBESITY-RELATED METABOLIC DISEASES. CONCLUSIONS: ALTHOUGH FURTHER RESEARCH IS NEEDED TO DRAW FIRM CONCLUSIONS, THERE IS INCREASING EVIDENCE ABOUT MICRORNAS AS POTENTIAL BIOMARKERS FOR WEIGHT LOSS AND RESPONSE TO INTERVENTION STRATEGIES IN OBESITY.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
7    74  28 A MULTIDISCIPLINARY APPROACH AND CURRENT PERSPECTIVE OF NONALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW. IN RECENT TIMES, NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BEEN CONSIDERED ONE OF THE MAJOR CAUSES OF LIVER DISEASE ACROSS THE WORLD. NAFLD IS DEFINED AS THE DEPOSITION OF TRIGLYCERIDES IN THE LIVER AND IS ASSOCIATED WITH OBESITY AND METABOLIC SYNDROME. HYPERINSULINEMIA, INSULIN RESISTANCE (IR), FATTY LIVER, HEPATOCYTE INJURY, UNBALANCED PROINFLAMMATORY CYTOKINES, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, LIVER INFLAMMATION, AND FIBROSIS ARE THE MAIN PATHOGENESIS IN NAFLD. RECENT STUDIES SUGGEST THAT THE ACTION OF INTESTINAL MICROBIOTA THROUGH CHRONIC INFLAMMATION, INCREASED INTESTINAL PERMEABILITY, AND ENERGY UPTAKE PLAYS A VITAL ROLE IN NAFLD. MOREOVER, POLYCYSTIC OVARIAN SYNDROME ALSO CAUSES NAFLD DEVELOPMENT THROUGH IR. AGE, GENDER, RACE, ETHNICITY, SLEEP, DIET, SEDENTARY LIFESTYLE, AND GENETIC AND EPIGENETIC PATHWAYS ARE SOME CONTRIBUTING FACTORS OF NAFLD THAT CAN EXACERBATE THE RISK OF LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA (HCC) AND EVENTUALLY LEAD TO DEATH. NAFLD HAS VARIOUS PRESENTATIONS, INCLUDING FATIGUE, UNEXPLAINED WEIGHT LOSS, BLOATING, UPPER ABDOMINAL PAIN, DECREASED APPETITE, HEADACHE, ANXIETY, POOR SLEEP, INCREASED THIRST, PALPITATION, AND A FEELING OF WARMTH. SOME STUDIES HAVE SHOWN THAT NAFLD WITH SEVERE CORONAVIRUS DISEASE 2019 (COVID-19) HAS POOR OUTCOMES. THE GOLD STANDARD FOR NAFLD DIAGNOSIS IS LIVER BIOPSY. OTHER DIAGNOSTIC TOOLS ARE IMAGING TESTS, SERUM BIOMARKERS, MICROBIOTA MARKERS, AND TESTS FOR EXTRAHEPATIC COMPLICATIONS. THERE ARE NO SPECIFIC TREATMENTS FOR NAFLD. THEREFORE, THE MAIN CONCERN FOR NAFLD IS TREATING THE COMORBID CONDITIONS SUCH AS ANTI-DIABETIC AGENTS FOR TYPE 2 DIABETES MELLITUS, STATINS TO REDUCE HCC PROGRESSION, ANTIOXIDANTS TO PREVENT HEPATOCELLULAR DAMAGE, AND BARIATRIC SURGERY FOR PATIENTS WITH A BMI OF >40 KG/M(2) AND >35 KG/M(2) WITH COMORBIDITIES. LIFESTYLE AND DIETARY CHANGES ARE CONSIDERED PREVENTIVE STRATEGIES AGAINST NAFLD ADVANCEMENT. INADEQUATE TREATMENT OF NAFLD FURTHER LEADS TO CARDIAC CONSEQUENCES, SLEEP APNEA, CHRONIC KIDNEY DISEASE, AND INFLAMMATORY BOWEL DISEASE. IN THIS SYSTEMATIC REVIEW, WE HAVE BRIEFLY DISCUSSED THE RISK FACTORS, PATHOGENESIS, CLINICAL FEATURES, AND NUMEROUS CONSEQUENCES OF NAFLD. WE HAVE ALSO REVIEWED VARIOUS GUIDELINES FOR NAFLD DIAGNOSIS ALONG WITH EXISTING THERAPEUTIC STRATEGIES FOR THE MANAGEMENT AND PREVENTION OF THE DISEASE.	2022	
                                                                                                                                        
8  3915  28 LINE-1 IN OBESITY AND CARDIOMETABOLIC DISEASES: A SYSTEMATIC REVIEW. EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF OBESITY AND CARDIOMETABOLIC DISEASES, BY ACTIVATING OR SILENCING THE RELATED-GENES. SCIENTIFIC EVIDENCE HAS SUGGESTED THAT LINE-1 METHYLATION IS ASSOCIATED WITH BODY COMPOSITION AND OBESITY-RELATED DISEASES, INCLUDING INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE (CVD). IT ALSO HAS BEEN EVALUATED AS PREDICTOR OF WEIGHT LOSS. THE STUDIES' RESULTS ARE STILL CONFLICTING, AND POSITIVE AND NEGATIVE ASSOCIATIONS HAVE BEEN FOUND TO LINE-1 METHYLATION REGARDING ADIPOSITY AND CARDIOMETABOLIC MARKERS. OVERALL, THIS REVIEW PRESENTS OBSERVATIONAL (CROSS-SECTIONAL AND LONGITUDINAL) STUDIES AND INTERVENTIONS (DIET, EXERCISES, AND BARIATRIC SURGERY) THAT EVALUATED THE RELATIONSHIP OF THE LINE-1 METHYLATION WITH OBESITY, WEIGHT LOSS, DYSLIPIDEMIAS, HYPERTENSION, INSULIN RESISTANCE, CVD, AND METABOLIC SYNDROME. TEACHING POINTS EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF OBESITY AND CARDIOMETABOLIC DISEASES. MANY STUDIES HAVE RELATED METHYLATION OF LINE-1 WITH CARDIOMETABOLIC DISEASES; HOWEVER, THE RESULTS ARE STILL CONTROVERSIAL. THE RELATIONSHIP BETWEEN THE ETIOLOGY OF CHRONIC DISEASES AND THE METHYLATION OF LINE-1 IS NOT FULLY ELUCIDATED. WITH ADVANCES IN EPIGENETIC STUDIES, RELATED MECHANISMS MAY BE EARLY BIOMARKERS IN WEIGHT CHANGE AND CARDIOMETABOLIC RISK.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
9  2699  25 EXCESS BODY WEIGHT: NOVEL INSIGHTS INTO ITS ROLES IN OBESITY COMORBIDITIES. EXCESS BODY WEIGHT IS A GLOBAL HEALTH PROBLEM DUE TO SEDENTARY LIFESTYLE AND UNHEALTHY DIET, AFFECTING 2 BILLION POPULATION WORLDWIDE. OBESITY IS A MAJOR RISK FACTOR FOR METABOLIC DISEASES. NOTABLY, THE METABOLIC RISK OF OBESITY LARGELY DEPENDS ON BODY WEIGHT DISTRIBUTION, OF WHICH VISCERAL ADIPOSE TISSUES BUT NOT SUBCUTANEOUS FATS ARE CLOSELY ASSOCIATED WITH OBESITY COMORBIDITIES, INCLUDING TYPE 2 DIABETES, NON-ALCOHOLIC FATTY LIVER DISEASE, CARDIOVASCULAR DISEASE AND CERTAIN TYPES OF CANCER. LATEST MULTI-OMICS AND MECHANISTICAL STUDIES REPORTED THE CRUCIAL INVOLVEMENT OF GENETIC AND EPIGENETIC ALTERATIONS, ADIPOKINES DYSREGULATION, IMMUNITY CHANGES, IMBALANCE OF WHITE AND BROWN ADIPOSE TISSUES, AND GUT MICROBIAL DYSBIOSIS IN MEDIATING THE PATHOGENIC ASSOCIATION BETWEEN VISCERAL ADIPOSE TISSUES AND COMORBIDITIES. IN THIS REVIEW, WE EXPLORE THE EPIDEMIOLOGY OF EXCESS BODY WEIGHT AND THE UP-TO-DATE MECHANISM OF HOW EXCESS BODY WEIGHT AND OBESITY LEAD TO CHRONIC COMPLICATIONS. WE ALSO EXAMINE THE UTILIZATION OF VISCERAL FAT MEASUREMENT AS AN ACCURATE CLINICAL PARAMETER FOR RISK ASSESSMENT IN HEALTHY INDIVIDUALS AND CLINICAL OUTCOME PREDICTION IN OBESE SUBJECTS. IN ADDITION, CURRENT APPROACHES FOR THE PREVENTION AND TREATMENT OF EXCESS BODY WEIGHT AND ITS RELATED METABOLIC COMORBIDITIES ARE FURTHER DISCUSSED.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
10  4202  28 METABOLIC SYNDROME IN CHILDREN BORN SMALL-FOR-GESTATIONAL AGE. BEING BORN SMALL-FOR-GESTATIONAL AGE AND A RAPID INCREASE IN WEIGHT DURING EARLY CHILDHOOD AND INFANCY HAS BEEN STRONGLY LINKED WITH CHRONIC DISEASES, INCLUDING METABOLIC SYNDROME, WHICH HAS BEEN RELATED TO INTRAUTERINE LIFE ENVIRONMENT AND LINKED TO EPIGENETIC FETAL PROGRAMMING. METABOLIC SYNDROME INCLUDES WAIST CIRCUMFERENCE >/= 90(TH) PERCENTILE FOR AGE, SEX AND RACE, HIGHER LEVELS OF BLOOD PRESSURE, TRIGLYCERIDES AND FASTING GLUCOSE, AND LOW LEVELS OF HDL-CHOLESTEROL. INSULIN RESISTANCE MAY BE PRESENT AS EARLY AS 1 YEAR OF AGE, AND OBESITY AND/OR TYPE 2 DIABETES ARE MORE PREVALENT IN THOSE BORN SGA THAN THOSE BORN AGA. THE PROGRAMMING OF ADAPTIVE RESPONSES IN CHILDREN BORN SGA INCLUDES AN ASSOCIATION WITH INCREASED BLOOD PRESSURE, CHANGES IN ENDOTHELIAL FUNCTION, ARTERIAL PROPERTIES AND CORONARY DISEASE. EARLY INTERVENTIONS SHOULD BE DIRECTED TO APPROPRIATE MATERNAL NUTRITION, BEFORE AND DURING PREGNANCY, PROMOTION OF BREAST FEEDING, AND PREVENTION OF RAPID WEIGHT GAIN DURING INFANCY, AND TO PROMOTE A HEALTHY LIFESTYLE.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
11  2801  21 FEMALE OBESITY: SHORT- AND LONG-TERM CONSEQUENCES ON THE OFFSPRING. THE WORLDWIDE PREVALENCE OF OBESITY HAS RISEN OVER THE PAST FEW DECADES AND WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. PRE-PREGNANCY OBESITY AND EXCESSIVE GESTATIONAL WEIGHT GAIN INCREASE MISCARRIAGE RATES AND OBSTETRIC AND NEONATAL COMPLICATIONS, WHICH RESULT IN A LOWER HEALTHY LIVE BIRTH RATE. IN ADDITION TO ITS NEGATIVE CONSEQUENCES FOR THE MOTHER, OBESITY HAS BEEN SHOWN TO BE AN IMPORTANT RISK FACTOR FOR CHRONIC ILLNESSES, SUCH AS CARDIOVASCULAR DISEASE, METABOLIC SYNDROME AND TYPE 2 DIABETES IN THE ADOLESCENCE AND ADULTHOOD OF THE OFFSPRING. MOREOVER, MATERNAL OBESITY CAUSES PSYCHOLOGICAL PROBLEMS, PHYSICAL DISABILITIES AND HIGHER HEALTHCARE COSTS. FETAL PROGRAMMING OF METABOLIC FUNCTION INDUCED BY OBESITY, THROUGH PHYSIOLOGICAL AND/OR EPIGENETIC MECHANISMS, MAY HAVE AN INTERGENERATIONAL EFFECT AND COULD, THUS, PERPETUATE OBESITY IN THE NEXT GENERATION. IN ORDER TO BREAK THIS VICIOUS CIRCLE AND AVOID SERIOUS SHORT- AND LONG-TERM NEGATIVE OUTCOMES FOR BOTH MOTHERS AND FETUSES, THE PREVENTION AND ADEQUATE MANAGEMENT OF OBESITY AND GESTATIONAL WEIGHT GAIN ARE ESSENTIAL.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
12  4711  30 NON-ALCOHOLIC FATTY LIVER DISEASE IN OBESE CHILDREN AND ADOLESCENTS: A ROLE FOR NUTRITION? NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BECOME THE MOST COMMON CAUSE OF CHRONIC LIVER DISEASE IN CHILDREN, PARALLELING THE INCREASING PREVALENCE OF OBESITY WORLDWIDE. THE PATHOGENESIS OF PAEDIATRIC NAFLD IS NOT FULLY UNDERSTOOD, BUT IT IS KNOWN THAT OBESITY, NUTRITION, LIFESTYLE VARIABLES, GENETIC AND EPIGENETIC FACTORS MAY BE CAUSALLY INVOLVED IN THE DEVELOPMENT OF THIS COMMON METABOLIC LIVER DISEASE. IN PARTICULAR, OBESITY AND NUTRITION ARE AMONG THE STRONGEST RISK FACTORS FOR PAEDIATRIC NAFLD, WHICH MAY EXERT THEIR ADVERSE HEPATIC EFFECTS ALREADY BEFORE BIRTH. EXCESS ENERGY INTAKE INDUCES HYPERTROPHY AND HYPERPLASIA OF ADIPOSE TISSUE WITH SUBSEQUENT DEVELOPMENT OF SYSTEMIC INSULIN RESISTANCE, WHICH IS ANOTHER IMPORTANT RISK FACTOR FOR NAFLD. DIET COMPOSITION AND IN PARTICULAR SIMPLE CARBOHYDRATE INTAKE (ESPECIALLY HIGH FRUCTOSE INTAKE) MAY PROMOTE THE DEVELOPMENT OF NAFLD, WHEREAS NON-DIGESTIBLE CARBOHYDRATES (DIETARY FIBER), BY AFFECTING GUT MICROBIOTA, MAY FAVOUR THE INTEGRITY OF GUT WALL AND REDUCE INFLAMMATION, OPPOSING THIS PROCESS. SATURATED FAT INTAKE MAY ALSO PROMOTE NAFLD DEVELOPMENT, WHEREAS UNSATURATED FAT INTAKE HAS SOME BENEFICIAL EFFECTS. PROTEIN INTAKE DOES NOT SEEM TO AFFECT THE DEVELOPMENT OF NAFLD, BUT FURTHER INVESTIGATION IS NEEDED. IN CONCLUSION, LIFESTYLE MODIFICATIONS TO INDUCE WEIGHT LOSS, THROUGH DIET AND PHYSICAL ACTIVITY, REMAIN THE MAINSTAY OF TREATMENT FOR PAEDIATRIC NAFLD. THE USE OF DIETARY SUPPLEMENTS, SUCH AS OMEGA-3 FATTY ACIDS AND PROBIOTICS, NEEDS FURTHER STUDY BEFORE RECOMMENDATION.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
13  2789  29 FACTORS INFLUENCING EPIGENETIC MECHANISMS: IS THERE A ROLE FOR BARIATRIC SURGERY? EPIGENETICS IS THE INTERACTION BETWEEN THE GENOME AND ENVIRONMENTAL STIMULI CAPABLE OF INFLUENCING GENE EXPRESSION DURING DEVELOPMENT AND AGING. A LARGE NUMBER OF STUDIES HAVE SHOWN THAT METABOLIC DISEASES ARE HIGHLY ASSOCIATED WITH EPIGENETIC ALTERATIONS, SUGGESTING THAT EPIGENETIC FACTORS MAY PLAY A CENTRAL ROLE IN OBESITY. TO INVESTIGATE THESE RELATIONSHIPS, WE FOCUS OUR ATTENTION ON THE MOST COMMON EPIGENETIC MODIFICATIONS THAT OCCUR IN OBESITY, INCLUDING DNA METHYLATION AND POST-TRANSLATIONAL MODIFICATIONS OF HISTONES. WE ALSO CONSIDER BARIATRIC SURGERY AS AN EPIGENETIC FACTOR, EVALUATING HOW THE ANATOMIC AND PHYSIOLOGIC MODIFICATIONS INDUCED BY THESE SURGICAL TECHNIQUES CAN CHANGE GENE EXPRESSION. HERE WE DISCUSS THE IMPORTANCE OF EPIGENETIC MECHANISMS IN CHRONIC DISEASE AND CANCER, AND THE ROLE OF EPIGENETIC DISTURBANCES IN OBESITY, WITH A FOCUS ON THE ROLE OF BARIATRIC SURGERY.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
14  4080  16 MATERNAL LIFESTYLE INTERVENTIONS: TARGETING PRECONCEPTION HEALTH. ABOUT ONE-THIRD OF WOMEN OF REPRODUCTIVE AGE ARE OBESE, PREDISPOSING BOTH MOTHER AND BABY TO UNFAVOURABLE PREGNANCY OUTCOMES AND INITIATING AN INTERGENERATIONAL CYCLE OF CHRONIC METABOLIC DISORDERS. HERE WE SUMMARISE RECENT RESEARCH ON THE INFLUENCE OF MATERNAL METABOLIC HEALTH ON OFFSPRING SUSCEPTIBILITY TO FUTURE CARDIOMETABOLIC DISEASES. CURRENT PRIMARY LIFESTYLE APPROACHES (I.E., DIET AND EXERCISE INTERVENTIONS) TO HALT THE SUCCESSION OF INHERITED AND EPIGENETIC METABOLIC ABNORMALITIES HAVE MET WITH LIMITED SUCCESS DUE TO LATE IMPLEMENTATION, POOR ADHERENCE, AND/OR GENERIC GUIDELINES. IN OUR OPINION, SUCH INTERVENTIONS MUST COMMENCE PRIOR TO CONCEPTION TO IMPROVE BOTH MATERNAL AND CHILD HEALTH OUTCOMES, WITH NEW APPROACHES URGENTLY NEEDED TO INCREASE ADHERENCE TO PRIMARY LIFESTYLE CHANGES AMONG REPRODUCTIVE-AGE WOMEN.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
15  5366  21 RECENT ADVANCES IN LEAN NAFLD. AS THE PREDOMINANT TYPE OF CHRONIC LIVER DISEASE, THE GROWING PREVALENCE OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BECOME A CONCERN WORLDWIDE. ALTHOUGH OBESITY PLAYS THE MOST PIVOTAL ROLE IN NAFLD, APPROXIMATELY 10-20% OF INDIVIDUALS WITH NAFLD WHO ARE NOT OVERWEIGHT OR OBESE (BMI < 25 KG/M2, OR BMI < 23 KG/M2 IN ASIANS) HAVE "LEAN NAFLD." LEAN INDIVIDUALS WITH NAFLD HAVE A LOWER PREVALENCE OF DIABETES, HYPERTENSION, HYPERTRIGLYCERIDEMIA, CENTRAL OBESITY, AND METABOLIC SYNDROME THAN NONLEAN INDIVIDUALS WITH NAFLD, BUT HIGHER FIBROSIS SCORES AND RATES OF CARDIOVASCULAR MORBIDITY AND ALL-CAUSE MORTALITY IN ADVANCED STAGES. THE PATHOPHYSIOLOGICAL MECHANISMS OF LEAN NAFLD REMAIN POORLY UNDERSTOOD. STUDIES HAVE SHOWN THAT LEAN NAFLD IS MORE CORRELATED WITH FACTORS SUCH AS ENVIRONMENTAL, GENETIC SUSCEPTIBILITY, AND EPIGENETIC REGULATION. THIS REVIEW WILL EXAMINE THE WAY IN WHICH THE RESEARCH PROGRESS AND CHARACTERISTIC OF LEAN NAFLD, AND EXPLORE THE FUNCTION OF EPIGENETIC MODIFICATION TO PROVIDE THE BASIS FOR THE CLINICAL TREATMENT AND DIAGNOSIS OF LEAN NAFLD.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
16  2881  30 FUTURE PERSPECTIVES OF PERSONALIZED WEIGHT LOSS INTERVENTIONS BASED ON NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA. AS OBESITY HAS BECOME A MAJOR GLOBAL PUBLIC HEALTH CHALLENGE, A LARGE NUMBER OF STUDIES HAVE ANALYZED DIFFERENT STRATEGIES AIMED AT INDUCING A NEGATIVE ENERGY BALANCE AND, CONSEQUENTLY, BODY WEIGHT LOSS. HOWEVER, MOST EXISTING WEIGHT LOSS PROGRAMS ARE GENERALLY UNSUCCESSFUL, SO SEVERAL INTERVENTIONS HAVE BEEN CARRIED OUT TO IDENTIFY PHYSIOLOGIC AND BEHAVIORAL FACTORS CONCERNING THIS VARIABILITY IN ORDER TO IMPLEMENT MORE PERSONALIZED TREATMENT. NOWADAYS, AN INDIVIDUALIZED APPROACH IS BEING PROPOSED THROUGH SO-CALLED PERSONALIZED NUTRITION, WHEREBY NOT ONLY THE PHENOTYPE BUT ALSO THE GENOTYPE IS USED FOR CUSTOMIZED NUTRITION TREATMENT. REGARDING BODY WEIGHT REGULATION, APPROXIMATELY 70 POLYMORPHISMS HAVE BEEN IDENTIFIED IN OR NEAR GENES RELATED TO ENERGY EXPENDITURE, APPETITE, ADIPOGENESIS, INSULIN RESISTANCE, AND LIPID METABOLISM. ALTHOUGH PERSONALIZED NUTRITION REFERS MAINLY TO GENETIC MAKEUP, RECENT ADVANCES IN THE INVESTIGATION OF THE EPIGENOME AND THE MICROBIOME OPEN THE DOOR TO IMPLEMENT MORE PERSONALIZED RECOMMENDATIONS FOR BODY WEIGHT MANAGEMENT. IN THIS CONTEXT, RECENT STUDIES HAVE DEMONSTRATED THE EXISTENCE OF SEVERAL EPIGENETIC MARKERS THAT MAY MODIFY GENE EXPRESSION AND COULD BE INVOLVED IN THE OUTCOME OF WEIGHT LOSS INTERVENTIONS. MOREOVER, DIFFERENT STUDIES HAVE SHOWN THAT DIETARY INTERVENTIONS COULD AFFECT THE COMPOSITION OF GUT MICROBIOTA AND HAVE AN IMPACT ON BODY WEIGHT. THE INTEGRATION OF NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA MAY LEAD TO THE DESIGN OF MORE PERSONALIZED DIETARY TREATMENTS TO PREVENT CHRONIC DISEASES AND TO OPTIMIZE THE INDIVIDUAL'S RESPONSE TO DIETARY INTERVENTIONS.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
17  4504  27 MOTHER'S PRE-PREGNANCY BMI AND PLACENTAL CANDIDATE MIRNAS: FINDINGS FROM THE ENVIRONAGE BIRTH COHORT. THERE IS INCREASING EVIDENCE THAT THE PREDISPOSITION FOR DEVELOPMENT OF CHRONIC DISEASES ARISES AT THE EARLIEST TIMES OF LIFE. IN THIS CONTEXT, MATERNAL PRE-PREGNANCY WEIGHT MIGHT MODIFY FETAL METABOLISM AND THE CHILD'S PREDISPOSITION TO DEVELOP DISEASE LATER IN LIFE. THE AIM OF THIS STUDY IS TO INVESTIGATE THE ASSOCIATION BETWEEN MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) AND MIRNA ALTERATIONS IN PLACENTAL TISSUE AT BIRTH. IN 211 MOTHER-NEWBORN PAIRS FROM THE ENVIRONAGE BIRTH COHORT, WE ASSESSED PLACENTAL EXPRESSION OF SEVEN MIRNAS IMPORTANT IN CRUCIAL CELLULAR PROCESSES IMPLICATED IN ADIPOGENESIS AND/OR OBESITY. MULTIPLE LINEAR REGRESSION MODELS WERE USED TO ADDRESS THE ASSOCIATIONS BETWEEN PRE-PREGNANCY BMI AND PLACENTAL CANDIDATE MIRNA EXPRESSION. MATERNAL PRE-PREGNANCY BMI AVERAGED (+/-SD) 23.9 (+/-4.1) KG/M(2). IN NEWBORN GIRLS (NOT IN BOYS) PLACENTAL MIR-20A, MIR-34A AND MIR-222 EXPRESSION WAS LOWER WITH HIGHER MATERNAL PRE-PREGNANCY BMI. IN ADDITION, THE ASSOCIATION BETWEEN MATERNAL PRE-PREGNANCY BMI AND PLACENTAL EXPRESSION OF THESE MIRNAS IN GIRLS WAS MODIFIED BY GESTATIONAL WEIGHT GAIN. THE LOWER EXPRESSION OF THESE MIRNAS IN PLACENTA IN ASSOCIATION WITH PRE-PREGNANCY BMI, WAS ONLY EVIDENT IN MOTHERS WITH LOW WEIGHT GAIN (<14 KG). THE PLACENTAL EXPRESSION OF MIR-20A, MIR-34A, MIR-146A, MIR-210 AND MIR-222 MAY PROVIDE A SEX-SPECIFIC BASIS FOR EPIGENETIC EFFECTS OF PRE-PREGNANCY BMI.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
18    13  34 360-DEGREE PERSPECTIVES ON OBESITY. ALARMING STATISTICS SHOW THAT THE NUMBER OF PEOPLE AFFECTED BY EXCESSIVE WEIGHT HAS SURPASSED 2 BILLION, REPRESENTING APPROXIMATELY 30% OF THE WORLD'S POPULATION. THE AIM OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF ONE OF THE MOST SERIOUS PUBLIC HEALTH PROBLEMS, CONSIDERING THAT OBESITY REQUIRES AN INTEGRATIVE APPROACH THAT TAKES INTO ACCOUNT ITS COMPLEX ETIOLOGY, INCLUDING GENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS. ONLY AN UNDERSTANDING OF THE CONNECTIONS BETWEEN THE MANY CONTRIBUTORS TO OBESITY AND THE SYNERGY BETWEEN TREATMENT INTERVENTIONS CAN ENSURE SATISFACTORY OUTCOMES IN REDUCING OBESITY. MECHANISMS SUCH AS OXIDATIVE STRESS, CHRONIC INFLAMMATION, AND DYSBIOSIS PLAY A CRUCIAL ROLE IN THE PATHOGENESIS OF OBESITY AND ITS ASSOCIATED COMPLICATIONS. COMPOUNDING FACTORS SUCH AS THE DELETERIOUS EFFECTS OF STRESS, THE NOVEL CHALLENGE POSED BY THE OBESOGENIC DIGITAL (FOOD) ENVIRONMENT, AND THE STIGMA ASSOCIATED WITH OBESITY SHOULD NOT BE OVERLOOKED. PRECLINICAL RESEARCH IN ANIMAL MODELS HAS BEEN INSTRUMENTAL IN ELUCIDATING THESE MECHANISMS, AND TRANSLATION INTO CLINICAL PRACTICE HAS PROVIDED PROMISING THERAPEUTIC OPTIONS, INCLUDING EPIGENETIC APPROACHES, PHARMACOTHERAPY, AND BARIATRIC SURGERY. HOWEVER, MORE STUDIES ARE NECESSARY TO DISCOVER NEW COMPOUNDS THAT TARGET KEY METABOLIC PATHWAYS, INNOVATIVE WAYS TO DELIVER THE DRUGS, THE OPTIMAL COMBINATIONS OF LIFESTYLE INTERVENTIONS WITH ALLOPATHIC TREATMENTS, AND, LAST BUT NOT LEAST, EMERGING BIOLOGICAL MARKERS FOR EFFECTIVE MONITORING. WITH EACH PASSING DAY, THE OBESITY CRISIS TIGHTENS ITS GRIP, THREATENING NOT ONLY INDIVIDUAL LIVES BUT ALSO BURDENING HEALTHCARE SYSTEMS AND SOCIETIES AT LARGE. IT IS HIGH TIME WE TOOK ACTION AS WE CONFRONT THE URGENT IMPERATIVE TO ADDRESS THIS ESCALATING GLOBAL HEALTH CHALLENGE HEAD-ON.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
19  4886  27 OVERWEIGHT AND OBESITY BEFORE, DURING AND AFTER PREGNANCY: PART 1: PATHOPHYSIOLOGY, MOLECULAR BIOLOGY AND EPIGENETIC CONSEQUENCES. OVERWEIGHT AND OBESITY BEFORE CONCEPTION AS WELL AS EXCESSIVE WEIGHT GAIN DURING PREGNANCY ARE ASSOCIATED WITH ENDOCRINOLOGICAL CHANGES OF MOTHER AND FETUS. INSULIN RESISTANCE PHYSIOLOGICALLY INCREASES DURING PREGNANCY, ADDITIONAL OBESITY FURTHER INCREASES INSULIN RESISTANCE. IN COMBINATION WITH REDUCED INSULIN SECRETION THIS LEADS TO GESTATIONAL DIABETES WHICH MAY DEVELOP INTO TYPE-2-DIABETES. THE ADIPOSE TISSUE PRODUCES TNF-ALPHA, INTERLEUKINS AND LEPTIN AND UPREGULATES THESE ADIPOKINES. INSULIN RESISTANCE AND OBESITY INDUCE INFLAMMATORY PROCESSES AND VASCULAR DYSFUNCTION, WHICH EXPLAINS THE INCREASED RATE OF PREGNANCY-RELATED HYPERTENSION AND PRE-ECLAMPSIA IN OBESE PREGNANT WOMEN. BETWEEN 14 AND 28 GESTATIONAL WEEKS, THE FETAL ADIPOSE TISSUE IS GENERATED AND THE NUMBER OF FAT LOBULES IS DETERMINED. THEREAFTER, AN INCREASE IN ADIPOSE TISSUE IS ARRANGED BY AN ENLARGEMENT OF THE LOBULES (HYPERTROPHY), OR EVEN AN INCREASE IN THE NUMBER OF FAT CELLS (HYPERPLASIA). HUMAN AND ANIMAL STUDIES HAVE SHOWN THAT MATERNAL OBESITY "PROGRAMMES" THE OFFSPRING FOR FURTHER OBESITY AND CHRONIC DISEASE. PREGNANT WOMEN, MIDWIVES, PHYSICIANS AND HEALTH CARE POLITICIANS SHOULD BE BETTER INFORMED ABOUT PREVENTION, PATHOPHYSIOLOGICAL MECHANISMS, AND THE BURDEN FOR SOCIETY CAUSED BY OBESITY BEFORE, DURING AND AFTER PREGNANCY.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
20  5104  16 POLYCYSTIC OVARIAN SYNDROME. WOMEN WITH PCOS PRESENT WITH SIGNS OF CHRONIC ANOVULATION, HYPERANDROGENISM, AND METABOLIC ABNORMALITIES. THE NIH RECENTLY EMBRACED THE ROTTERDAM CRITERIA TO BROADLY IDENTIFY ALL THE PHENOTYPES OF PCOS. WOMEN WITH PCOS ARE OFTEN OBESE WITH INSULIN RESISTANCE AND HENCE HAVE AN INCREASED SUSCEPTIBILITY TO GLUCOSE INTOLERANCE AND TYPE 2 DIABETES. FUTURE RESEARCH SHOULD FOCUS ON THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL DETERMINANTS OF PCOS TO DEVELOP NEW THERAPIES TO ADDRESS THE PREVENTION OF THIS DISORDER AND ITS LONG-TERM COMPLICATIONS.	2015