1 3915 99 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 2 6462 40 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 3 6109 33 THE EPIGENETIC AGING, OBESITY, AND LIFESTYLE. THE PREVALENCE OF OBESITY HAS DRAMATICALLY INCREASED WORLDWIDE OVER THE PAST DECADES. AGING-RELATED CHRONIC CONDITIONS, SUCH AS TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE, ARE MORE PREVALENT IN INDIVIDUALS WITH OBESITY, THUS REDUCING THEIR LIFESPAN. EPIGENETIC CLOCKS, THE NEW METRICS OF BIOLOGICAL AGE BASED ON DNA METHYLATION PATTERNS, COULD BE CONSIDERED A REFLECTION OF THE STATE OF ONE'S HEALTH. SEVERAL ENVIRONMENTAL EXPOSURES AND LIFESTYLE FACTORS CAN INDUCE EPIGENETIC AGING ACCELERATIONS, INCLUDING OBESITY, THUS LEADING TO AN INCREASED RISK OF AGE-RELATED DISEASES. THE INSIGHT INTO THE COMPLEX LINK BETWEEN OBESITY AND AGING MIGHT HAVE SIGNIFICANT IMPLICATIONS FOR THE PROMOTION OF HEALTH AND THE MITIGATION OF FUTURE DISEASE RISK. THE PRESENT NARRATIVE REVIEW TAKES INTO ACCOUNT THE INTERACTION BETWEEN EPIGENETIC AGING AND OBESITY, SUGGESTING THAT EPIGENOME MAY BE AN INTRIGUING TARGET FOR AGE-RELATED PHYSIOLOGICAL CHANGES AND THAT ITS MODIFICATION COULD INFLUENCE AGING AND PROLONG A HEALTHY LIFESPAN. THEREFORE, WE HAVE FOCUSED ON DNA METHYLATION AGE AS A CLINICAL BIOMARKER, AS WELL AS ON THE POTENTIAL REVERSAL OF EPIGENETIC AGE USING A PERSONALIZED DIET- AND LIFESTYLE-BASED INTERVENTION. 2022 4 4662 38 NEW DEVELOPMENTS IN THE PATHOGENESIS OF OBESITY-INDUCED HYPERTENSION. OBESITY IS A DISORDER THAT DEVELOPS FROM THE INTERACTION BETWEEN GENOTYPE AND ENVIRONMENT INVOLVING SOCIAL, BEHAVIORAL, CULTURAL, AND PHYSIOLOGICAL FACTORS. OBESITY INCREASES THE RISK FOR TYPE 2 DIABETES MELLITUS, HYPERTENSION, CARDIOVASCULAR DISEASE, CANCER, MUSCULOSKELETAL DISORDERS, CHRONIC KIDNEY AND PULMONARY DISEASE. ALTHOUGH OBESITY IS CLEARLY ASSOCIATED WITH AN INCREASED PREVALENCE OF HYPERTENSION, MANY OBESE INDIVIDUALS MAY NOT DEVELOP HYPERTENSION. PROTECTING FACTORS MAY EXIST AND IT IS IMPORTANT TO UNDERSTAND WHY OBESITY IS NOT ALWAYS RELATED TO HYPERTENSION. THE AIM OF THIS REVIEW IS TO HIGHLIGHT THE KNOWLEDGE GAP FOR THE ASSOCIATION BETWEEN OBESITY, HYPERTENSION, AND POTENTIAL GENETIC AND RACIAL DIFFERENCES OR ENVIRONMENTAL FACTORS THAT MAY PROTECT OBESE PATIENTS AGAINST THE DEVELOPMENT OF HYPERTENSION AND OTHER CO-MORBIDITIES. SPECIFIC MUTATIONS IN THE LEPTIN AND THE MELANINOCORTIN RECEPTOR GENES IN ANIMAL MODELS OF OBESITY WITHOUT HYPERTENSION, THE ACTIONS OF ALPHA-MELANOCYTE STIMULATING HORMONE, AND SNS ACTIVITY IN OBESITY-RELATED HYPERTENSION MAY PROMOTE RECOGNITION OF PROTECTIVE AND PROMOTING FACTORS FOR HYPERTENSION IN OBESITY. FURTHERMORE, GENE-ENVIRONMENT INTERACTIONS MAY HAVE THE POTENTIAL TO MODIFY GENE EXPRESSION AND EPIGENETIC MECHANISMS COULD ALSO CONTRIBUTE TO THE HERITABILITY OF OBESITY-INDUCED HYPERTENSION. FINALLY, DIFFERENCES IN NUTRITION, GUT MICROBIOTA, EXPOSURE TO SUN LIGHT AND EXERCISE MAY PLAY AN IMPORTANT ROLE IN THE PRESENCE OR ABSENCE OF HYPERTENSION IN OBESITY. 2015 5 5076 33 PHYSIOLOGICAL AND ENVIRONMENTAL FACTORS AFFECTING CANCER RISK AND PROGNOSIS IN OBESITY. OBESITY RESULTS FROM A CHRONIC EXCESSIVE ACCUMULATION OF ADIPOSE TISSUE DUE TO A LONG-TERM IMBALANCE BETWEEN ENERGY INTAKE AND EXPENDITURE. AVAILABLE EPIDEMIOLOGICAL AND CLINICAL DATA STRONGLY SUPPORT THE LINKS BETWEEN OBESITY AND CERTAIN CANCERS. EMERGING CLINICAL AND EXPERIMENTAL FINDINGS HAVE IMPROVED OUR UNDERSTANDING OF THE ROLES OF KEY PLAYERS IN OBESITY-ASSOCIATED CARCINOGENESIS SUCH AS AGE, SEX (MENOPAUSE), GENETIC AND EPIGENETIC FACTORS, GUT MICROBIOTA AND METABOLIC FACTORS, BODY SHAPE TRAJECTORY OVER LIFE, DIETARY HABITS, AND GENERAL LIFESTYLE. IT IS NOW WIDELY ACCEPTED THAT THE CANCER-OBESITY RELATIONSHIP DEPENDS ON THE SITE OF CANCER, THE SYSTEMIC INFLAMMATORY STATUS, AND MICRO ENVIRONMENTAL PARAMETERS SUCH AS LEVELS OF INFLAMMATION AND OXIDATIVE STRESS IN TRANSFORMING TISSUES. WE HEREBY REVIEW RECENT ADVANCES IN OUR UNDERSTANDING OF CANCER RISK AND PROGNOSIS IN OBESITY WITH RESPECT TO THESE PLAYERS. WE HIGHLIGHT HOW THE LACK OF THEIR CONSIDERATION CONTRIBUTED TO THE CONTROVERSY OVER THE LINK BETWEEN OBESITY AND CANCER IN EARLY EPIDEMIOLOGICAL STUDIES. FINALLY, THE LESSONS AND CHALLENGES OF INTERVENTIONS FOR WEIGHT LOSS AND BETTER CANCER PROGNOSIS, AND THE MECHANISMS OF WEIGHT GAIN IN SURVIVORS ARE ALSO DISCUSSED. 2023 6 2699 35 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 7 1388 26 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE: NON-INVASIVE ASSESSMENT OF CARDIOVASCULAR RISK. THE PREVALENCE AND BURDEN OF DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE ON GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT IS ALREADY HEAVY AND STILL RISING. DIABETES MELLITUS BY ITSELF IS LINKED TO ADVERSE CARDIOVASCULAR EVENTS, AND THE PRESENCE OF CONCOMITANT CHRONIC KIDNEY DISEASE FURTHER AMPLIFIES CARDIOVASCULAR RISK. THE CULMINATION OF TRADITIONAL (MALE GENDER, SMOKING, ADVANCED AGE, OBESITY, ARTERIAL HYPERTENSION AND DYSLIPIDEMIA) AND NON-TRADITIONAL RISK FACTORS (ANEMIA, INFLAMMATION, PROTEINURIA, VOLUME OVERLOAD, MINERAL METABOLISM ABNORMALITIES, OXIDATIVE STRESS, ETC.) CONTRIBUTES TO ADVANCED ATHEROSCLEROSIS AND INCREASED CARDIOVASCULAR RISK. TO DECREASE THE MORBIDITY AND MORTALITY OF THESE PATIENTS DUE TO CARDIOVASCULAR CAUSES, TIMELY AND EFFICIENT CARDIOVASCULAR RISK ASSESSMENT IS OF HUGE IMPORTANCE. CARDIOVASCULAR RISK ASSESSMENT CAN BE BASED ON LABORATORY PARAMETERS, IMAGING TECHNIQUES, ARTERIAL STIFFNESS PARAMETERS, ANKLE-BRACHIAL INDEX AND 24 H BLOOD PRESSURE MEASUREMENTS. NEWER METHODS INCLUDE EPIGENETIC MARKERS, SOLUBLE ADHESION MOLECULES, CYTOKINES AND MARKERS OF OXIDATIVE STRESS. IN THIS REVIEW, THE AUTHORS PRESENT SEVERAL NON-INVASIVE METHODS OF CARDIOVASCULAR RISK ASSESSMENT IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE. 2021 8 6469 42 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 9 4087 37 MATERNAL OBESITY INCREASES THE RISK OF METABOLIC DISEASE AND IMPACTS RENAL HEALTH IN OFFSPRING. OBESITY, TOGETHER WITH INSULIN RESISTANCE, PROMOTES MULTIPLE METABOLIC ABNORMALITIES AND IS STRONGLY ASSOCIATED WITH AN INCREASED RISK OF CHRONIC DISEASE INCLUDING TYPE 2 DIABETES (T2D), HYPERTENSION, CARDIOVASCULAR DISEASE, NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND CHRONIC KIDNEY DISEASE (CKD). THE INCIDENCE OF OBESITY CONTINUES TO RISE IN ASTRONOMICAL PROPORTIONS THROUGHOUT THE WORLD AND AFFECTS ALL THE DIFFERENT STAGES OF THE LIFESPAN. IMPORTANTLY, THE PROPORTION OF WOMEN OF REPRODUCTIVE AGE WHO ARE OVERWEIGHT OR OBESE IS INCREASING AT AN ALARMING RATE AND HAS POTENTIAL RAMIFICATIONS FOR OFFSPRING HEALTH AND DISEASE RISK. EVIDENCE SUGGESTS A STRONG LINK BETWEEN THE INTRAUTERINE ENVIRONMENT AND DISEASE PROGRAMMING. THE CURRENT REVIEW WILL DESCRIBE THE IMPORTANCE OF THE INTRAUTERINE ENVIRONMENT IN THE DEVELOPMENT OF METABOLIC DISEASE, INCLUDING KIDNEY DISEASE. IT WILL DETAIL THE KNOWN MECHANISMS OF FETAL PROGRAMMING, INCLUDING THE ROLE OF EPIGENETIC MODULATION. THE EVIDENCE FOR THE ROLE OF MATERNAL OBESITY IN THE DEVELOPMENTAL PROGRAMMING OF CKD IS DERIVED MOSTLY FROM OUR RODENT MODELS WHICH WILL BE DESCRIBED. THE CLINICAL IMPLICATION OF SUCH FINDINGS WILL ALSO BE DISCUSSED. 2018 10 3848 32 IS EPIGENETICS AN IMPORTANT LINK BETWEEN EARLY LIFE EVENTS AND ADULT DISEASE? BACKGROUND: EPIGENETIC MECHANISMS PROVIDE ONE POTENTIAL EXPLANATION FOR HOW ENVIRONMENTAL INFLUENCES IN EARLY LIFE CAUSE LONG-TERM CHANGES IN CHRONIC DISEASE SUSCEPTIBILITY. WHEREAS EPIGENETIC DYSREGULATION IS INCREASINGLY IMPLICATED IN VARIOUS RARE DEVELOPMENTAL SYNDROMES AND CANCER, THE ROLE OF EPIGENETICS IN COMPLEX CHRONIC DISEASES, SUCH AS CARDIOVASCULAR DISEASE, TYPE 2 DIABETES AND OBESITY, REMAINS LARGELY UNCHARACTERIZED. EXTENSIVE WORK IN ANIMAL MODELS IS REQUIRED TO DEVELOP SPECIFIC HYPOTHESES THAT CAN BE PRACTICABLY TESTED IN HUMANS. ANIMAL MODELS: WE HAVE DEVELOPED A MOUSE MODEL SHOWING THAT METHYL DONOR SUPPLEMENTATION PREVENTS TRANSGENERATIONAL AMPLIFICATION OF OBESITY, SUGGESTING A ROLE FOR DNA METHYLATION IN THE DEVELOPMENTAL ESTABLISHMENT OF BODY WEIGHT REGULATION. CONCLUSIONS: COUPLING SUCH MODELS WITH RECENTLY DEVELOPED EPIGENOMIC TECHNOLOGIES SHOULD ULTIMATELY ENABLE US TO DETERMINE IF EPIGENETICS IS AN IMPORTANT LINK BETWEEN EARLY LIFE EVENTS AND ADULT DISEASE. 2009 11 5821 38 STRESS IN OBESITY AND ASSOCIATED METABOLIC AND CARDIOVASCULAR DISORDERS. OBESITY HAS SIGNIFICANT IMPLICATIONS FOR HEALTHCARE, SINCE IT IS A MAJOR RISK FACTOR FOR BOTH TYPE 2 DIABETES AND THE METABOLIC SYNDROME. THIS SYNDROME IS A COMMON AND COMPLEX DISORDER COMBINING OBESITY, DYSLIPIDEMIA, HYPERTENSION, AND INSULIN RESISTANCE. IT IS ASSOCIATED WITH HIGH ATHEROSCLEROTIC CARDIOVASCULAR RISK, WHICH CAN ONLY PARTIALLY BE EXPLAINED BY ITS COMPONENTS. THEREFORE, TO EXPLAIN HOW OBESITY CONTRIBUTES TO THE DEVELOPMENT OF METABOLIC AND CARDIOVASCULAR DISORDERS, MORE AND BETTER INSIGHT IS REQUIRED INTO THE EFFECTS OF PERSONAL AND ENVIRONMENTAL STRESS ON DISEASE PROCESSES. IN THIS PAPER, WE SHOW THAT OBESITY IS A CHRONIC INFLAMMATORY DISEASE, WHICH HAS MANY MOLECULAR MECHANISMS IN COMMON WITH ATHEROSCLEROSIS. FURTHERMORE, WE FOCUS ON THE ROLE OF OXIDATIVE STRESS ASSOCIATED WITH OBESITY IN THE DEVELOPMENT OF THE METABOLIC SYNDROME. WE DISCUSS HOW SEVERAL STRESS CONDITIONS ARE RELATED TO INFLAMMATION AND OXIDATIVE STRESS IN ASSOCIATION WITH OBESITY AND ITS COMPLICATIONS. WE ALSO EMPHASIZE THE RELATION BETWEEN STRESS CONDITIONS AND THE DEREGULATION OF EPIGENETIC CONTROL MECHANISMS BY MEANS OF MICRORNAS AND SHOW HOW THIS IMPAIRMENT FURTHER CONTRIBUTES TO THE DEVELOPMENT OF OBESITY, CLOSING THE VICIOUS CIRCLE. FINALLY, WE DISCUSS THE LIMITATIONS OF CURRENT ANTI-INFLAMMATION AND ANTIOXIDANT THERAPY TO TREAT OBESITY. 2012 12 4801 29 OBESITY AND INSULIN RESISTANCE: ASSOCIATIONS WITH CHRONIC INFLAMMATION, GENETIC AND EPIGENETIC FACTORS. BACKGROUND: OBESITY IS KNOWN TO BE A MULTIFACTORIAL DISEASE. IN ITS PATHOGENESIS, DIFFERENT FACTORS SUCH AS CHRONIC INFLAMMATION, OXIDATIVE STRESS, INSULIN RESISTANCE, GENETIC FACTORS, ENVIRONMENTAL EFFECTS, VEGETATIVE DISTURBANCE, AND UNBALANCED NUTRITION PLAY A SIGNIFICANT ROLE. METHODOLOGY: THIS STUDY DESCRIBES THE ASSOCIATION OF OBESITY AND INSULIN RESISTANCE WITH CHRONIC INFLAMMATION, GENETIC, AND EPIGENETIC FACTORS. PREVIOUS LITERATURE HAS BEEN REVIEWED TO EXPLAIN THE RELATION OF OBESITY WITH THOSE FACTORS INVOLVED IN CHRONIC LOW-GRADE INFLAMMATION AND INSULIN. RESULTS: OBESITY IS ASSOCIATED WITH A DECREASE IN GHRELIN SECRETION, ELEVATED PLASMA LEPTIN LEVELS, OXIDATIVE STRESS, INCREASED MACROPHAGE PHAGOCYTIC ACTIVITY, AND THE INDUCTION OF PROINFLAMMATORY SYNTHESIS OF CYTOKINES AND INTERFERON-GAMMA. OBESITY IS LINKED TO DECREASED LEVELS OF CYTOCHROME P450 (CYP) ENZYMES AND IMPAIRED DETOXIFICATION PROCESSES. DEFICIENCY OF VITAMINS AND MINERALS CAN ALSO PLAY A SIGNIFICANT ROLE IN THE DEVELOPMENT OF OXIDATIVE STRESS AND CHRONIC INFLAMMATION IN OBESITY. THERE IS EVIDENCE OF ASSOCIATIONS BETWEEN A GENETIC PREDISPOSITION TO OBESITY IN CHILDREN WITH ELEVATED LEVELS OF CERTAIN MIRNAS. CONCLUSION: THE PURPOSE OF THE PRESENT REVIEW IS AN ANALYSIS OF THE MULTIPLE FACTORS ASSOCIATED WITH OBESITY. 2021 13 3577 39 IMPACT OF NUTRITION ON TELOMERE HEALTH: SYSTEMATIC REVIEW OF OBSERVATIONAL COHORT STUDIES AND RANDOMIZED CLINICAL TRIALS. DIET, PHYSICAL ACTIVITY, AND OTHER LIFESTYLE FACTORS HAVE BEEN IMPLICATED IN THE PATHOPHYSIOLOGY OF SEVERAL CHRONIC DISEASES, BUT ALSO IN A LOWER TOTAL MORTALITY AND LONGER LIFE EXPECTANCY. ONE OF THE MECHANISMS IN WHICH DIET CAN REDUCE THE RISK OF DISEASE IS WITH REGARD TO ITS IMPACT ON TELOMERES. TELOMERE LENGTH (TL) IS HIGHLY CORRELATED TO CHRONOLOGICAL AGE AND METABOLIC STATUS. INDIVIDUALS WITH SHORTER TELOMERES ARE AT HIGHER RISK OF CHRONIC DISEASES AND MORTALITY. DIET MAY INFLUENCE TL BY SEVERAL MECHANISMS SUCH AS REGULATING OXIDATIVE STRESS AND INFLAMMATION OR MODULATING EPIGENETIC REACTIONS. THE PRESENT SYSTEMATIC REVIEW AIMS TO EXAMINE THE RESULTS FROM EPIDEMIOLOGIC AND CLINICAL TRIALS CONDUCTED IN HUMANS EVALUATING THE ROLE OF NUTRIENTS, FOOD GROUPS, AND DIETARY PATTERNS ON TL. WE ALSO DISCUSS THE POSSIBLE MECHANISMS OF ACTION THAT INFLUENCE THIS PROCESS, WITH THE PERSPECTIVE THAT TL COULD BE A NOVEL BIOMARKER INDICATING THE RISK OF METABOLIC DISTURBANCES AND AGE-RELATED DISEASES. THE AVAILABLE EVIDENCE SUGGESTS THAT SOME ANTIOXIDANT NUTRIENTS, THE CONSUMPTION OF FRUITS AND VEGETABLES, AND MEDITERRANEAN DIET ARE MAINLY ASSOCIATED WITH LONGER TELOMERES. HOWEVER, MOST OF THE EVIDENCE IS BASED ON HIGH HETEROGENIC OBSERVATIONAL STUDIES AND VERY FEW RANDOMIZED CLINICAL TRIALS (RCTS). THEREFORE, THE ASSOCIATIONS SUMMARIZED IN THE PRESENT REVIEW NEED TO BE CONFIRMED WITH LARGER PROSPECTIVE COHORT STUDIES AND BETTER-DESIGNED RCTS. 2020 14 4793 30 NUTRITIONAL FACTORS, DNA METHYLATION, AND RISK OF TYPE 2 DIABETES AND OBESITY: PERSPECTIVES AND CHALLENGES. A HEALTHY DIET IMPROVES LIFE EXPECTANCY AND HELPS TO PREVENT COMMON CHRONIC DISEASES SUCH AS TYPE 2 DIABETES (T2D) AND OBESITY. THE MECHANISMS DRIVING THESE EFFECTS ARE NOT FULLY UNDERSTOOD, BUT ARE LIKELY TO INVOLVE EPIGENETICS. EPIGENETIC MECHANISMS CONTROL GENE EXPRESSION, MAINTAINING THE DNA SEQUENCE, AND THEREFORE THE FULL GENOMIC INFORMATION INHERITED FROM OUR PARENTS, UNCHANGED. AN INTERESTING FEATURE OF EPIGENETIC CHANGES LIES IN THEIR DYNAMIC NATURE AND REVERSIBILITY. ACCORDINGLY, THEY ARE SUSCEPTIBLE TO CORRECTION THROUGH TARGETED INTERVENTIONS. HERE WE WILL REVIEW THE EVIDENCE SUPPORTING A ROLE FOR NUTRITIONAL FACTORS IN MEDIATING METABOLIC DISEASE RISK THROUGH DNA METHYLATION CHANGES. SPECIAL EMPHASIS WILL BE PLACED ON THE POTENTIAL OF USING DNA METHYLATION TRAITS AS BIOMARKERS TO PREDICT RISK OF OBESITY AND T2D AS WELL AS ON THEIR RESPONSE TO DIETARY AND PHARMACOLOGICAL (EPI-DRUG) INTERVENTIONS. 2019 15 1801 38 EFFECT OF MATERNAL DIET ON THE EPIGENOME: IMPLICATIONS FOR HUMAN METABOLIC DISEASE. THE RAPID INCREASE IN THE INCIDENCE OF CHRONIC NON-COMMUNICABLE DISEASES OVER THE PAST TWO DECADES CANNOT BE EXPLAINED SOLELY BY GENETIC AND ADULT LIFESTYLE FACTORS. THERE IS NOW CONSIDERABLE EVIDENCE THAT THE FETAL AND EARLY POSTNATAL ENVIRONMENT ALSO STRONGLY INFLUENCES THE RISK OF DEVELOPING SUCH DISEASES IN LATER LIFE. HUMAN STUDIES HAVE SHOWN THAT LOW BIRTH WEIGHT IS ASSOCIATED WITH AN INCREASED RISK OF CVD, TYPE II DIABETES, OBESITY AND HYPERTENSION, ALTHOUGH RECENT STUDIES HAVE SHOWN THAT OVER-NUTRITION IN EARLY LIFE CAN ALSO INCREASE SUSCEPTIBILITY TO FUTURE METABOLIC DISEASE. THESE FINDINGS HAVE BEEN REPLICATED IN A VARIETY OF ANIMAL MODELS, WHICH HAVE SHOWN THAT BOTH MATERNAL UNDER- AND OVER-NUTRITION CAN INDUCE PERSISTENT CHANGES IN GENE EXPRESSION AND METABOLISM WITHIN THE OFFSPRING. THE MECHANISM BY WHICH THE MATERNAL NUTRITIONAL ENVIRONMENT INDUCES SUCH CHANGES IS BEGINNING TO BE UNDERSTOOD AND INVOLVES THE ALTERED EPIGENETIC REGULATION OF SPECIFIC GENES. THE DEMONSTRATION OF A ROLE FOR ALTERED EPIGENETIC REGULATION OF GENES IN THE DEVELOPMENTAL INDUCTION OF CHRONIC DISEASES RAISES THE POSSIBILITY THAT NUTRITIONAL OR PHARMACEUTICAL INTERVENTIONS MAY BE USED TO MODIFY LONG-TERM CARDIO-METABOLIC DISEASE RISK AND COMBAT THIS RAPID RISE IN CHRONIC NON-COMMUNICABLE DISEASES. 2011 16 726 41 CAN TYPE 1 DIABETES BE AN UNEXPECTED COMPLICATION OF OBESITY? TYPE 1 DIABETES (T1D) IS ONE OF THE MOST COMMON CHRONIC AUTOIMMUNE DISEASES, CHARACTERIZED BY ABSOLUTE INSULIN DEFICIENCY CAUSED VIA INFLAMMATORY DESTRUCTION OF THE PANCREATIC BETA-CELL. GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS PLAY A ROLE IN THE DEVELOPMENT OF DISEASES. ALMOST (1/5) OF CASES INVOLVE PEOPLE UNDER THE AGE OF 20. IN RECENT YEARS, THE INCIDENCE OF BOTH T1D AND OBESITY HAS BEEN INCREASING, ESPECIALLY AMONG CHILDREN, ADOLESCENTS, AND YOUNG PEOPLE. IN ADDITION, ACCORDING TO THE LATEST STUDY, THE PREVALENCE OF OVERWEIGHT OR OBESITY IN PEOPLE WITH T1D HAS INCREASED SIGNIFICANTLY. THE RISK FACTORS OF WEIGHT GAIN INCLUDED USING EXOGENOUS INSULIN, INTENSIFYING INSULIN THERAPY, FEAR OF HYPOGLYCEMIA AND RELATED DECREASE IN PHYSICAL ACTIVITY, AND PSYCHOLOGICAL FACTORS, SUCH AS EMOTIONAL EATING AND BINGE EATING. IT HAS ALSO BEEN SUGGESTED THAT T1D MAY BE A COMPLICATION OF OBESITY. THE RELATIONSHIP BETWEEN BODY SIZE IN CHILDHOOD, INCREASE IN BODY MASS INDEX VALUES IN LATE ADOLESCENCE AND THE DEVELOPMENT OF T1D IN YOUNG ADULTHOOD IS CONSIDERED. MOREOVER, THE COEXISTENCE OF T1D AND T2D IS INCREASINGLY OBSERVED, THIS SITUATION IS CALLED DOUBLE OR HYBRID DIABETES. THIS IS ASSOCIATED WITH AN INCREASED RISK OF THE EARLIER DEVELOPMENT OF DYSLIPIDEMIA, CARDIOVASCULAR DISEASES, CANCER, AND CONSEQUENTLY A SHORTENING OF LIFE. THUS, THE PURPOSE OF THIS REVIEW WAS TO SUMMARIZE THE RELATIONSHIPS BETWEEN OVERWEIGHT OR OBESITY AND T1D. 2023 17 6861 33 [OBESITY: A MODEL OF COMPLEX INTERACTIONS BETWEEN GENETICS AND ENVIRONMENT]. OBESITY IS EXPLAINED BY THE JOINT ACTIONS OF GENETIC SUSCEPTIBILITY AND ENVIRONMENTAL FACTORS, SUCH AS A WESTERNIZED LIFESTYLE (SEDENTARY LIFESTYLE, CALORIE-DENSE FOODS), INDUCING AN OBESOGENIC ENVIRONMENT. THE SEARCH FOR OBESITY SUSCEPTIBILITY GENES REMAINS COMPLEX, DESPITE RECENT ADAVANCES MADE IN THE OBESITY GENETICS FIELD. EXCEPT VERY RARE MONOGENIC TYPE OBESITY, COMMON OBESITY IS THOUGHT TO BE POLYGENIC AND THE GENETIC CONTRIBUTION TO INTERINDIVIDUAL VARIATION IN COMMON OBESITY HAS BEEN ESTIMATED AT 40-70 %. THE GENOME-WIDE ASSOCIATION STUDIES HAVE LED TO IDENTIFY NUMEROUS GENETIC LOCI ASSOCIATED WITH BODY MASS INDEX AND OBESITY RISK. HOWEVER, THE PREDICTIVE VALUE OF THESE LOCI TO THE OBESITY RISK AT THE POPULATION LEVEL REMAINS LOW. FINALLY, THE INFLUENCE OF ENVIRONMENTAL FACTORS ON GENETIC SUSCEPTIBILITY TO WEIGHT GAIN IS ALSO RELATED TO EPIGENETIC FACTORS. NUTRITIONAL UNBALANCE DURING FETAL DEVELOPMENT MAY CHANGE THE INTRAUTERINE ENVIRONMENT AND LEAD TO ALTERED GENE EXPRESSION (FETAL PROGRAMMING) WITH ALTERATIONS IN DNA OR HISTONE METHYLATION RESULTING IN AN INCREASED SUSCEPTIBILITY TO CHRONIC DISEASE IN ADULTHOOD, SUCH AS OBESITY. 2012 18 6165 32 THE GLOBAL DIABETES EPIDEMIC AS A CONSEQUENCE OF LIFESTYLE-INDUCED LOW-GRADE INFLAMMATION. THE RECENT MAJOR INCREASE IN THE GLOBAL INCIDENCE OF TYPE 2 DIABETES SUGGESTS THAT MOST CASES OF THIS DISEASE ARE CAUSED BY CHANGES IN ENVIRONMENT AND LIFESTYLE. ALL MAJOR RISK FACTORS FOR TYPE 2 DIABETES (OVERNUTRITION, LOW DIETARY FIBRE, SEDENTARY LIFESTYLE, SLEEP DEPRIVATION AND DEPRESSION) HAVE BEEN FOUND TO INDUCE LOCAL OR SYSTEMIC LOW-GRADE INFLAMMATION THAT IS USUALLY TRANSIENT OR MILDER IN INDIVIDUALS NOT AT RISK FOR TYPE 2 DIABETES. BY CONTRAST, INFLAMMATORY RESPONSES TO LIFESTYLE FACTORS ARE MORE PRONOUNCED AND PROLONGED IN INDIVIDUALS AT RISK OF TYPE 2 DIABETES AND APPEAR TO OCCUR ALSO IN THE PANCREATIC ISLETS. CHRONIC LOW-GRADE INFLAMMATION WILL EVENTUALLY LEAD TO OVERT DIABETES IF COUNTER-REGULATORY CIRCUITS TO INFLAMMATION AND METABOLIC STRESS ARE COMPROMISED BECAUSE OF A GENETIC AND/OR EPIGENETIC PREDISPOSITION. HENCE, IT IS NOT THE LIFESTYLE CHANGE PER SE BUT A DEFICIENT COUNTER-REGULATORY RESPONSE IN PREDISPOSED INDIVIDUALS WHICH IS CRUCIAL TO DISEASE PATHOGENESIS. NOVEL APPROACHES OF INTERVENTION MAY TARGET THESE DEFICIENT DEFENCE MECHANISMS. 2010 19 44 33 A COMPREHENSIVE REVIEW ON HIGH -FAT DIET-INDUCED DIABETES MELLITUS: AN EPIGENETIC VIEW. MODERN LIFESTYLE, GENETICS, NUTRITIONAL OVERLOAD THROUGH HIGH-FAT DIET ATTRIBUTED PREVALENCE AND DIABETES OUTCOMES WITH VARIOUS COMPLICATIONS PRIMARILY DUE TO OBESITY IN WHICH ENERGY-DENSE DIETS FREQUENTLY AFFECT METABOLIC HEALTH. ONE POSSIBLE ISSUE USUALLY ASSOCIATED WITH ELEVATED CHRONIC FAT INTAKE IS INSULIN RESISTANCE, AND HYPERGLYCEMIA CONSTITUTES AN IMPORTANT FUNCTION IN ALTERING THE CARBOHYDRATES AND LIPIDS METABOLISM. SIMILARLY, IN ASSESSING HUMAN SUSCEPTIBILITY TO WEIGHT GAIN AND OBESITY, GENETIC VARIATIONS PLAY A CENTRAL ROLE, CONTRIBUTING TO KEEN INTEREST IN IDENTIFYING THE POSSIBLE ROLE OF EPIGENETICS AS A MEDIATOR OF GENE-ENVIRONMENTAL INTERACTIONS INFLUENCING THE PRODUCTION OF TYPE 2 DIABETES MELLITUS AND ITS RELATED CONCERNS. EPIGENETIC MODIFICATIONS ASSOCIATED WITH THE ACCEPTANCE OF A SEDENTARY LIFESTYLE AND ENVIRONMENTAL STRESS FACTORS IN RESPONSE TO ENERGY INTAKE AND EXPENDITURE IMBALANCES COMPLEMENT GENETIC ALTERATIONS AND LEAD TO THE PRODUCTION AND ADVANCEMENT OF METABOLIC DISORDERS SUCH AS DIABETES AND OBESITY. METHYLATION OF DNA, HISTONE MODIFICATIONS, AND INCREASES IN THE EXPRESSION OF NON-CODING RNAS CAN RESULT IN REDUCED TRANSCRIPTIONAL ACTIVITY OF KEY BETA-CELL GENES THUS CREATING INSULIN RESISTANCE. EPIGENETICS CONTRIBUTE TO CHANGES IN THE EXPRESSION OF THE UNDERLYING INSULIN RESISTANCE AND INSUFFICIENCY GENE NETWORKS, ALONG WITH LOW-GRADE OBESITY-RELATED INFLAMMATION, INCREASED ROS GENERATION, AND DNA DAMAGE IN MULTIORGANS. THIS REVIEW FOCUSED ON EPIGENETIC MECHANISMS AND METABOLIC REGULATIONS ASSOCIATED WITH HIGH-FAT DIET (HFD)-INDUCED DIABETES MELLITUS. 2022 20 2584 35 EPIGENETICS OF OBESITY. OBESITY IS A METABOLIC DISEASE, WHICH IS BECOMING AN EPIDEMIC HEALTH PROBLEM: IT HAS BEEN RECENTLY DEFINED IN TERMS OF GLOBAL PANDEMIC. OVER THE YEARS, THE APPROACHES THROUGH FAMILY, TWINS AND ADOPTION STUDIES LED TO THE IDENTIFICATION OF SOME CAUSAL GENES IN MONOGENIC FORMS OF OBESITY BUT THE ORIGINS OF THE PANDEMIC OF OBESITY CANNOT BE CONSIDERED ESSENTIALLY DUE TO GENETIC FACTORS, BECAUSE HUMAN GENOME IS NOT LIKELY TO CHANGE IN JUST A FEW YEARS. EPIGENETIC STUDIES HAVE OFFERED IN RECENT YEARS VALUABLE TOOLS FOR THE UNDERSTANDING OF THE WORLDWIDE SPREAD OF THE PANDEMIC OF OBESITY. THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS-DNA METHYLATION, HISTONE TAILS, AND MIRNAS MODIFICATIONS-IN THE DEVELOPMENT OF OBESITY IS MORE AND MORE EVIDENT. IN THE EPIGENETIC LITERATURE, THERE ARE EVIDENCES THAT THE ENTIRE EMBRYO-FETAL AND PERINATAL PERIOD OF DEVELOPMENT PLAYS A KEY ROLE IN THE PROGRAMMING OF ALL HUMAN ORGANS AND TISSUES. THEREFORE, THE MOLECULAR MECHANISMS INVOLVED IN THE EPIGENETIC PROGRAMMING REQUIRE A NEW AND GENERAL PATHOGENIC PARADIGM, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE THEORY, TO EXPLAIN THE CURRENT EPIDEMIOLOGICAL TRANSITION, THAT IS, THE WORLDWIDE INCREASE OF CHRONIC, DEGENERATIVE, AND INFLAMMATORY DISEASES SUCH AS OBESITY, DIABETES, CARDIOVASCULAR DISEASES, NEURODEGENERATIVE DISEASES, AND CANCER. OBESITY AND ITS RELATED COMPLICATIONS ARE MORE AND MORE ASSOCIATED WITH ENVIRONMENTAL POLLUTANTS (OBESOGENS), GUT MICROBIOTA MODIFICATIONS AND UNBALANCED FOOD INTAKE, WHICH CAN INDUCE, THROUGH EPIGENETIC MECHANISMS, WEIGHT GAIN, AND ALTERED METABOLIC CONSEQUENCES. 2016