1  4806 122 OBESITY AND METABOLIC SYNDROME ASSOCIATED WITH SYSTEMIC INFLAMMATION AND THE IMPACT ON THE MALE REPRODUCTIVE SYSTEM. OBESITY AND METABOLIC SYNDROME (METS) ARE GLOBAL EPIDEMICS, DRIVEN BY AN OBESOGENIC ENVIRONMENT. THIS IS MEDIATED BY COMPLEX UNDERLYING PATHOPHYSIOLOGY, IN WHICH CHRONIC INFLAMMATION IS AN IMPORTANT AETIOLOGICAL AND MECHANISTIC PHENOMENON. A SHIFT TOWARDS A SUBCLINICAL T(H) 1-LYMPHOCYTE MEDIATED INNATE AND CHRONIC INFLAMMATORY RESPONSE IS WELL DEFINED IN OBESITY AND METS, DEMONSTRATED IN MULTIPLE SYSTEMS INCLUDING VISCERAL ADIPOSITY, BRAIN (HYPOTHALAMUS), MUSCLES, VASCULATURE, LIVER, PANCREAS, TESTES, EPIDIDYMIS, PROSTATE AND SEMINAL FLUID. INFLAMMATORY CYTOKINES DISRUPT THE HYPOTHALAMIC-PITUITARY-TESTES AXIS AND STEROIDOGENESIS CASCADES (HYPOGONADOTROPIC HYPOGONADISM), SPERMATOGENESIS (POOR SEMEN PARAMETERS, INCLUDING DNA FRAGMENTATION AND DETRIMENTAL EPIGENETIC MODIFICATION) AND RESULTS IN SUBCLINICAL PROSTATITIS AND PROSTATE HYPERPLASIA. THIS REVIEW AIMS TO HIGHLIGHT THE ROLE OF CHRONIC INFLAMMATION IN OBESITY AND METS, CYTOKINES IN MALE REPRODUCTIVE PHYSIOLOGY AND PATHOPHYSIOLOGY, THE IMPACT ON STEROIDOGENESIS AND SPERMATOGENESIS, PROSTATE PATHOLOGY AND ERECTILE DYSFUNCTION. CURRENTLY, IT IS RECOMMENDED THAT CLINICAL ASSESSMENT OF MALE INFERTILITY AND REPRODUCTIVE DYSFUNCTION IN OBESE AND METS PATIENTS INCLUDES INFLAMMATION ASSESSMENT (HIGHLY SENSITIVE C-REACTIVE PROTEIN), AND APPROPRIATE ADVICE AND THERAPEUTIC OPTIONS ARE INCORPORATED IN THE MANAGEMENT OPTIONS. HOWEVER, THE MECHANISMS AND THERAPEUTIC OPTIONS REMAIN POORLY UNDERSTOOD AND REQUIRE SIGNIFICANT INTERDISCIPLINARY RESEARCH TO IDENTIFY POTENTIAL NOVEL THERAPEUTIC STRATEGIES.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
2  4188  36 METABOLIC ASSOCIATED FATTY LIVER DISEASE IN CHILDREN AND ADOLESCENTS: MECHANISMS OF A SILENT EPIDEMIC AND THERAPEUTIC OPTIONS. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS NOW IDENTIFIED AS A HEPATIC SIGN OF METABOLIC SYNDROME AND IS THE MOST FREQUENT CAUSE OF CHRONIC LIVER DISEASE IN ALL AGES. IT IS ASSUMED THAT A GENETIC PREDISPOSITION ASSOCIATED WITH EPIGENETIC FACTORS PARTICIPATES IN THE EVOLUTION OF THIS CONDITION. VISCERAL OBESITY AND INSULIN RESISTANCE (IR) HAVE ALWAYS BEEN CONSIDERED THE MOST IMPORTANT CAUSATIVE FACTORS OF METABOLIC SYNDROME (METS) AND NAFLD, BUT CURRENTLY, THE INTERACTION BETWEEN GENETIC HERITAGE AND ENVIRONMENTAL FACTORS IS INCREASINGLY CONSIDERED FUNDAMENTAL IN THE GENESIS OF METABOLIC DISORDERS ASSOCIATED WITH NAFLD. IN FACT, IN PATIENTS WITH NAFLD, INSULIN RESISTANCE, ARTERIAL HYPERTENSION, ABDOMINAL OBESITY, DYSLIPIDEMIA AND REDUCED INTESTINAL PERMEABILITY HAVE OFTEN BEEN FOUND, AS WELL AS A HIGHER PREVALENCE OF CORONARY ARTERY DISEASE, OBSTRUCTIVE SLEEP APNEA, POLYCYSTIC OVARY SYNDROME AND OSTEOPENIA, WHICH DEFINE A METS FRAMEWORK. EARLY DIAGNOSIS IS NEEDED TO PREVENT DISEASE PROGRESSION THROUGH PRIMARILY LIFESTYLE INTERVENTIONS. UNFORTUNATELY, AT PRESENT, THERE ARE NO MOLECULES RECOMMENDED FOR PEDIATRIC PATIENTS. HOWEVER, SEVERAL NEW DRUGS ARE IN CLINICAL TRIALS. FOR THIS REASON, TARGETED STUDIES ON THE INTERACTION BETWEEN GENETICS AND ENVIRONMENTAL FACTORS INVOLVED IN THE DEVELOPMENT OF NAFLD AND METS AND ON THE PATHOGENETIC MECHANISMS THAT DETERMINE THE EVOLUTION IN NON-ALCOHOLIC STEATOHEPATITIS (NASH), SHOULD BE IMPLEMENTED. THEREFORE, IT IS DESIRABLE THAT FUTURE STUDIES MAY BE USEFUL IN IDENTIFYING PATIENTS AT RISK OF DEVELOPING NAFLD AND METS EARLY.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
3   848  37 CHILDHOOD TRAUMA, THE STRESS RESPONSE AND METABOLIC SYNDROME: A FOCUS ON DNA METHYLATION. CHILDHOOD TRAUMA (CT) IS WELL ESTABLISHED AS A POTENT RISK FACTOR FOR THE DEVELOPMENT OF MENTAL DISORDERS. HOWEVER, THE POTENTIAL OF ADVERSE EARLY EXPERIENCES TO EXERT CHRONIC AND PROFOUND EFFECTS ON PHYSICAL HEALTH, INCLUDING ABERRANT METABOLIC PHENOTYPES, HAS ONLY BEEN MORE RECENTLY EXPLORED. AMONG THESE CONSEQUENCES IS METABOLIC SYNDROME (METS), WHICH IS CHARACTERISED BY AT LEAST THREE OF FIVE RELATED CARDIOMETABOLIC TRAITS: HYPERTENSION, INSULIN RESISTANCE/HYPERGLYCAEMIA, RAISED TRIGLYCERIDES, LOW HIGH-DENSITY LIPOPROTEIN AND CENTRAL OBESITY. THE DELETERIOUS EFFECTS OF CT ON HEALTH OUTCOMES MAY BE PARTIALLY ATTRIBUTABLE TO DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS, WHICH COORDINATES THE RESPONSE TO STRESS, AND THE CONSEQUENT FOSTERING OF A PRO-INFLAMMATORY ENVIRONMENT. EPIGENETIC TAGS, SUCH AS DNA METHYLATION, WHICH ARE SENSITIVE TO ENVIRONMENTAL INFLUENCES PROVIDE A MEANS WHEREBY THE EFFECTS OF CT CAN BE BIOLOGICALLY EMBEDDED AND PERSIST INTO ADULTHOOD TO AFFECT HEALTH AND WELL-BEING. THE METHYLOME REGULATES THE TRANSCRIPTION OF GENES INVOLVED IN THE STRESS RESPONSE, METABOLISM AND INFLAMMATION. THIS NARRATIVE REVIEW EXAMINES THE EVIDENCE FOR DNA METHYLATION IN CT AND METS IN ORDER TO IDENTIFY SHARED NEUROENDOCRINE AND IMMUNE CORRELATES THAT MAY MEDIATE THE INCREASED RISK OF METS FOLLOWING CT EXPOSURE. OUR REVIEW SPECIFICALLY HIGHLIGHTS DIFFERENTIAL METHYLATION OF FKBP5, THE GENE THAT ENCODES FK506-BINDING PROTEIN 51 AND HAS PLEIOTROPIC EFFECTS ON STRESS RESPONDING, INFLAMMATION AND ENERGY METABOLISM, AS A CENTRAL CANDIDATE TO UNDERSTAND THE MOLECULAR AETIOLOGY UNDERLYING CT-ASSOCIATED METS RISK.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
4  4586  27 NAFLD AT THE INTERFACE OF THE MOTHER-INFANT DYAD. THIS REVIEW AIMS TO FOCUS THE LINKS EXISTING BETWEEN SEVERAL ASPECTS OF THE MOTHER-CHILD DYAD IN THE INTRICATE PLAYGROUND OF OBESITY AND METABOLIC SYNDROME (METS), INCLUDING ITS HEPATIC COMPONENT, THE NON- ALCOHOLIC FATTY LIVER DISEASE (NAFLD). IN RECENT YEARS HUMAN AND ANIMAL MODEL STUDIES HAVE SHOWN THAT DIETARY INTERVENTIONS IN MOTHERS AND OFFSPRING CAN BE SUCCESSFUL IN REDUCING THE RISK OF NAFLD DEVELOPMENT. EVIDENCES ALSO CONCERN THE NEW CONCEPT OF A REAL INTERGENERATIONAL TRANSMISSION OF PREDISPOSITION TO METABOLIC DISORDERS. CERTAIN GENES, SUCH AS SIRT1 AND PNPLA3, AND SOME EPIGENETIC MODIFICATIONS, INCLUDING MICRO RNAS FUNCTION, SEEM TO BE RESPONSIBLE FOR FETAL REPROGRAMMING IN THE SETTING OF MATERNAL OBESITY. THESE MODIFIERS APPEAR TO BE POTENTIAL THERAPEUTIC TARGETS TO REDUCE THE RISK OF FUTURE METABOLIC DYSFUNCTIONS. CONTROLLING ANTEPARTUM HYPERGLYCEMIA, PREVENTING GESTATIONAL DIABETES, AND AVOIDING EXCESSIVE WEIGHT GAIN DURING PREGNANCY CAN HELP REDUCE THE RELENTLESS EPIDEMIC OF CHILDHOOD OBESITY AND NAFLD. ALSO, THE COMPOSITION OF THE INTESTINAL MICROBIOTA SEEMS TO BE RELATED TO THE DEVELOPMENT OF METABOLIC DISORDERS IN THE OFFSPRING. SEVERAL STUDIES SHOW THAT BREASTFED INFANTS HAVE A MICROBIAL SIGNATURE DIFFERENT FROM FORMULA-FED INFANTS. MUCH INTERESTINGLY, PROLONGED BREASTFEEDING IS BENEFICIAL NOT ONLY FOR THE NEWBORN AND HIS HEALTH IN ADULT LIFE, BUT ALSO FOR THE MOTHERS' HEALTH. MATERNAL BENEFITS INCLUDE REDUCING THE RISK OF DEVELOPING CHRONIC DISEASES, SUCH AS DIABETES MELLITUS, MYOCARDIAL INFARCTION AND NAFLD AS WELL. IN CONCLUSION, ALL ABOVE MECHANISMS APPEAR TO INTERVENE SYNERGISTICALLY AND MAY ACT AS MODIFIABLE RISK FACTORS FOR INFANT AND MOTHER NAFLD.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
5   378  28 AN EPIGENETIC MAP OF AGE-ASSOCIATED AUTOSOMAL LOCI IN NORTHERN EUROPEAN FAMILIES AT HIGH RISK FOR THE METABOLIC SYNDROME. BACKGROUND: THE PREVALENCE OF CHRONIC DISEASES SUCH AS CANCER, TYPE 2 DIABETES, METABOLIC SYNDROME (METS), AND CARDIOVASCULAR DISEASE INCREASES WITH AGE IN ALL POPULATIONS. EPIGENETIC FEATURES ARE HYPOTHESIZED TO PLAY IMPORTANT ROLES IN THE PATHOPHYSIOLOGY OF AGE-ASSOCIATED DISEASES, BUT A MAP OF THESE MARKERS IS LACKING. WE SEARCHED FOR GENOME-WIDE AGE-ASSOCIATED METHYLATION SIGNATURES IN PERIPHERAL BLOOD OF INDIVIDUALS AT HIGH RISKS FOR METS BY PROFILING 485,000 CPG SITES IN 192 INDIVIDUALS OF NORTHERN EUROPEAN ANCESTRY USING THE ILLUMINA HM450 ARRAY. SUBJECTS (AGES 6-85 YEARS) WERE PART OF SEVEN EXTENDED FAMILIES, AND 73% OF ADULTS AND 32% OF CHILDREN WERE OVERWEIGHT OR OBESE. RESULTS: WE FOUND 22,122 GENOME-WIDE SIGNIFICANT AGE-ASSOCIATED CPG SITES (P ALPHA=0.05 = 3.65 X 10(-7) AFTER CORRECTION FOR MULTIPLE TESTING) OF WHICH 14,155 ARE POSITIVELY ASSOCIATED WITH AGE WHILE 7,967 ARE NEGATIVELY ASSOCIATED. BY APPLYING A POSITIONAL DENSITY-BASED CLUSTERING ALGORITHM, WE GENERATED A MAP OF EPIGENETIC 'HOT-SPOTS' OF AGE-ASSOCIATED GENOMIC SEGMENTS, WHICH INCLUDE 290 AGE-ASSOCIATED DIFFERENTIALLY METHYLATED CPG CLUSTERS (ADMCS), OF WHICH 207 ARE POSITIVELY ASSOCIATED WITH AGE. GENE/PATHWAY ENRICHMENT ANALYSES WERE PERFORMED ON THESE CLUSTERS USING FATIGO. GENES LOCALIZED TO BOTH THE POSITIVELY (N = 241) AND NEGATIVELY (N = 16) AGE-ASSOCIATED CLUSTERS ARE SIGNIFICANTLY ENRICHED IN SPECIFIC KEGG PATHWAYS AND GO TERMS. THE MOST SIGNIFICANTLY ENRICHED PATHWAYS ARE THE HEDGEHOG SIGNALING PATHWAY (ADJUSTED P = 3.96 X 10(-3)) AND MATURITY-ONSET DIABETES OF THE YOUNG (MODY) (ADJUSTED P = 6.26 X 10(-3)) IN THE POSITIVE ADMCS AND TYPE I DIABETES MELLITUS (ADJUSTED P = 3.69 X 10(-7)) IN THE NEGATIVE ADMCS. WE ALSO IDENTIFIED SEVERAL EPIGENETIC LOCI WHOSE AGE-ASSOCIATED CHANGE RATES DIFFER BETWEEN SUBJECTS DIAGNOSED WITH METS AND THOSE WITHOUT. CONCLUSION: WE CONCLUDE THAT IN A FAMILY COHORT AT HIGH RISK FOR METS, AGE-ASSOCIATED EPIGENETIC FEATURES ENRICH IN BIOLOGICAL PATHWAYS IMPORTANT FOR DETERMINING THE FATE OF FAT CELLS AND FOR INSULIN PRODUCTION. WE ALSO OBSERVE THAT SEVERAL GENES KNOWN TO BE RELATED TO METS SHOW DIFFERENTIAL EPIGENETIC RESPONSE TO AGE IN INDIVIDUALS WITH AND WITHOUT METS.	2015	
                                                                                                                                                                                  
6  3750  26 INSULIN RESISTANCE IN POLYCYSTIC OVARY SYNDROME ACROSS VARIOUS TISSUES: AN UPDATED REVIEW OF PATHOGENESIS, EVALUATION, AND TREATMENT. POLYCYSTIC OVARY SYNDROME (PCOS) IS A COMMON ENDOCRINE DISORDER CHARACTERIZED BY CHRONIC OVULATION DYSFUNCTION AND OVERABUNDANCE OF ANDROGENS; IT AFFECTS 6-20% OF WOMEN OF REPRODUCTIVE AGE. PCOS INVOLVES VARIOUS PATHOPHYSIOLOGICAL FACTORS, AND AFFECTED WOMEN USUALLY HAVE SIGNIFICANT INSULIN RESISTANCE (IR), WHICH IS A MAJOR CAUSE OF PCOS. IR AND COMPENSATORY HYPERINSULINAEMIA HAVE DIFFERING PATHOGENESES IN VARIOUS TISSUES, AND IR VARIES AMONG DIFFERENT PCOS PHENOTYPES. GENETIC AND EPIGENETIC CHANGES, HYPERANDROGENAEMIA, AND OBESITY AGGRAVATE IR. INSULIN SENSITIZATION DRUGS ARE A NEW TREATMENT MODALITY FOR PCOS. WE SEARCHED PUBMED, GOOGLE SCHOLAR, ELSEVIER, AND UPTODATE DATABASES IN THIS REVIEW, AND FOCUSED ON THE PATHOGENESIS OF IR IN WOMEN WITH PCOS AND THE PATHOPHYSIOLOGY OF IR IN VARIOUS TISSUES. IN ADDITION, THE REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF THE CURRENT PROGRESS IN THE EFFICACY OF INSULIN SENSITIZATION THERAPY IN THE MANAGEMENT OF PCOS, PROVIDING THE LATEST EVIDENCE FOR THE CLINICAL TREATMENT OF WOMEN WITH PCOS AND IR.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
7  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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
8  4202  21 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
9  5104  18 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
10  4804  46 OBESITY AND MALE INFERTILITY: MECHANISMS AND MANAGEMENT. OBESITY IS CONSIDERED A GLOBAL HEALTH PROBLEM AFFECTING MORE THAN A THIRD OF THE POPULATION. COMPLICATIONS OF OBESITY INCLUDE CARDIOVASCULAR DISEASES, TYPE 2 DIABETES MELLITUS, MALIGNANCY (INCLUDING PROSTATIC CANCER), NEURODEGENERATION AND ACCELERATED AGEING. IN MALES, THESE FURTHER INCLUDE ERECTILE DYSFUNCTION, POOR SEMEN QUALITY AND SUBCLINICAL PROSTATITIS. ALTHOUGH POORLY UNDERSTOOD, IMPORTANT MEDIATORS OF OBESITY THAT MAY INFLUENCE THE MALE REPRODUCTIVE SYSTEM INCLUDE HYPERINSULINEMIA, HYPERLEPTINEMIA, CHRONIC INFLAMMATION AND OXIDATIVE STRESS. OBESITY IS KNOWN TO DISRUPT MALE FERTILITY AND THE REPRODUCTION POTENTIAL, PARTICULARLY THROUGH ALTERATION IN THE HYPOTHALAMIC-PITUITARY-GONADAL AXIS, DISRUPTION OF TESTICULAR STEROIDOGENESIS AND METABOLIC DYSREGULATION, INCLUDING INSULIN, CYTOKINES AND ADIPOKINES. IMPORTANTLY, OBESITY AND ITS UNDERLYING MEDIATORS RESULT IN A NEGATIVE IMPACT ON SEMEN PARAMETERS, INCLUDING SPERM CONCENTRATION, MOTILITY, VIABILITY AND NORMAL MORPHOLOGY. MOREOVER, OBESITY INHIBITS CHROMATIN CONDENSATION, DNA FRAGMENTATION, INCREASES APOPTOSIS AND EPIGENETIC CHANGES THAT CAN BE TRANSFERRED TO THE OFFSPRING. THIS REVIEW DISCUSSES THE IMPACT OF OBESITY ON THE MALE REPRODUCTIVE SYSTEM AND FERTILITY, INCLUDING ASSOCIATED MECHANISMS. FURTHERMORE, WEIGHT MANAGEMENT STRATEGIES, LIFESTYLE CHANGES, PRESCRIPTION MEDICATION, AND COMPLEMENTARY AND ALTERNATIVE MEDICINE IN THE MANAGEMENT OF OBESITY-INDUCED SUBFERTILITY IS DISCUSSED.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
11  2801  23 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  6678  30 USING GENETIC BURDEN SCORES FOR GENE-BY-METHYLATION INTERACTION ANALYSIS ON METABOLIC SYNDROME IN AFRICAN AMERICANS. WITH THE RAPID ADVANCEMENT OF OMICS-BASED RESEARCH, PARTICULARLY BIG DATA SUCH AS GENOME- AND EPIGENOME-WIDE ASSOCIATION STUDIES THAT INCLUDE EXTENSIVE ENVIRONMENTAL AND CLINICAL VARIABLES, DATA ANALYTICS HAVE BECOME INCREASINGLY COMPLEX. RESEARCHERS FACE SIGNIFICANT CHALLENGES REGARDING HOW TO ANALYZE MULTIFACTORIAL DATA AND MAKE USE OF THE FINDINGS FOR CLINICAL TRANSLATION. THE PURPOSE OF THIS ARTICLE IS TO PROVIDE A SCIENTIFIC EXEMPLAR FOR USE OF GENETIC BURDEN SCORES AS A DATA ANALYSIS METHOD FOR STUDIES WITH BOTH GENOTYPE AND DNA METHYLATION DATA IN WHICH THE GOAL IS TO EVALUATE ASSOCIATIONS WITH CHRONIC CONDITIONS SUCH AS METABOLIC SYNDROME (METS). THIS STUDY INCLUDED 739 AFRICAN AMERICAN MEN AND WOMEN FROM THE GENETIC EPIDEMIOLOGY NETWORK OF ARTERIOPATHY STUDY WHO MET DIAGNOSTIC CRITERIA FOR METS AND HAD AVAILABLE GENETIC AND EPIGENETIC DATA. GENETIC BURDEN SCORES FOR EVALUATED GENES WERE NOT SIGNIFICANT AFTER MULTIPLE TESTING CORRECTIONS, BUT DNA METHYLATION AT 2 CPG SITES (DIHYDROOROTATE DEHYDROGENASE CG22381196 PFDR = .014; CTNNA3 CG00132141 PFDR = .043) WAS SIGNIFICANTLY ASSOCIATED WITH METS AFTER CONTROLLING FOR MULTIPLE COMPARISONS. INTERACTIONS BETWEEN THE MARGINALLY SIGNIFICANT CPG SITES AND BURDEN SCORES, HOWEVER, WERE NOT SIGNIFICANT. MORE WORK IS REQUIRED IN THIS AREA TO IDENTIFY INTERMEDIATE BIOLOGICAL PATHWAYS INFLUENCED BY ENVIRONMENTAL, GENETIC, AND EPIGENETIC VARIATION THAT MAY EXPLAIN THE HIGH PREVALENCE OF METS AMONG AFRICAN AMERICANS. THIS STUDY DOES SERVE, HOWEVER, AS AN EXAMPLE OF THE USE OF THE GENETIC BURDEN SCORE AS AN ALTERNATIVE DATA ANALYSIS APPROACH FOR COMPLEX STUDIES INVOLVING THE ANALYSIS OF GENETIC AND EPIGENETIC DATA SIMULTANEOUSLY.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
13  2699  29 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
14  5107  29 POLYCYSTIC OVARY SYNDROME: A BRAIN DISORDER CHARACTERIZED BY EATING PROBLEMS ORIGINATING DURING PUBERTY AND ADOLESCENCE. POLYCYSTIC OVARY SYNDROME (PCOS) IS AN ENDOCRINE CONDITION ASSOCIATED WITH REPRODUCTIVE AND PSYCHIATRIC DISORDERS, AND WITH OBESITY. EATING DISORDERS, SUCH AS BULIMIA AND RECURRENT DIETING, ARE ALSO LINKED TO PCOS. THEY CAN LEAD TO THE EPIGENETIC DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-GONADAL (HPG) AXIS, THEREBY IMPACTING ON OVARIAN FOLLICULOGENESIS. WE POSTULATE THAT PCOS IS INDUCED BY PSYCHOLOGICAL DISTRESS AND EPISODES OF OVEREATING AND/OR DIETING DURING PUBERTY AND ADOLESCENCE, WHEN BODY DISSATISFACTION AND EMOTIONAL DISTRESS ARE OFTEN PRESENT. WE PROPOSE THAT UPREGULATED ACTIVATION OF THE CENTRAL HPG AXIS DURING THIS PERIOD CAN BE EPIGENETICALLY ALTERED BY PSYCHOLOGICAL STRESSORS AND BY BULIMIA/RECURRENT DIETING, WHICH ARE COMMON DURING ADOLESCENCE AND WHICH CAN LEAD TO PCOS. THIS HYPOTHESIS IS BASED ON EVENTS THAT OCCUR DURING A LARGELY NEGLECTED STAGE OF FEMALE REPRODUCTIVE DEVELOPMENT. TO DATE, MOST RESEARCH INTO THE ORIGINS OF PCOS HAS FOCUSED ON THE PRENATAL INDUCTION OF THIS DISORDER, PARTICULARLY IN UTERO ANDROGENIZATION AND THE ROLE OF ANTI-MULLERIAN HORMONE. ESTABLISHING CAUSALITY IN OUR PERIPUBERTAL MODEL REQUIRES PROSPECTIVE COHORT STUDIES FROM INFANCY. MECHANISTIC STUDIES SHOULD CONSIDER THE ROLE OF THE GUT MICROBIOTA IN ADDITION TO THE EPIGENETIC REGULATION OF (NEURO) HORMONES. FINALLY, CLINICIANS SHOULD CONSIDER THE IMPORTANCE OF UNDERLYING CHRONIC PSYCHOLOGICAL DISTRESS AND EATING DISORDERS IN PCOS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
15  4892  28 OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: OXIDATIVE STRESS IN POLYCYSTIC OVARY SYNDROME. IN BRIEF: A GENETIC, EPIGENETIC, AND ENVIRONMENTAL ASSOCIATION EXISTS BETWEEN OXIDATIVE STRESS (OS) AND POLYCYSTIC OVARY SYNDROME (PCOS), EXPRESSED IN A MULTIFACETED CLINICAL PROFILE. THIS REVIEW SUMMARIZES AND DISCUSSES THE ROLE OF OS IN THE PATHOGENESIS OF PCOS SYNDROME, FOCUSING ON METABOLIC, REPRODUCTIVE, AND CANCER COMPLICATIONS. ABSTRACT: OXIDATIVE STRESS (OS), AN IMBALANCE BETWEEN OXIDANTS AND ANTIOXIDANTS IN CELLS, IS ONE OF MANY FACTORS PLAYING ESSENTIAL ROLES IN THE PATHOGENESIS OF POLYCYSTIC OVARY SYNDROME (PCOS). PCOS IS DESCRIBED MAINLY AS A DISPROPORTION OF REPRODUCTIVE HORMONES, LEADING TO CHRONIC ANOVULATION AND INFERTILITY IN WOMEN. INTERESTINGLY, OS IN PCOS MAY BE ASSOCIATED WITH MANY DISORDERS AND DISEASES. THIS REVIEW FOCUSES ON CHARACTERISTIC MARKERS OF OS IN PCOS AND THE RELATIONSHIP BETWEEN OS AND PCOS RELATED TO INSULIN RESISTANCE (IR), HYPERANDROGENEMIA, OBESITY, CHRONIC INFLAMMATION, CARDIOVASCULAR DISEASES, AND CANCER. INTERESTINGLY, IN PATIENTS WITH PCOS, AN INCREASE IN OXIDATIVE STATUS AND INSUFFICIENT COMPENSATION OF THE INCREASE IN ANTIOXIDANT STATUS BEFORE ANY CARDIOVASCULAR COMPLICATIONS ARE OBSERVED. MOREOVER, FREE RADICALS PROMOTE CARCINOGENESIS IN PCOS PATIENTS. HOWEVER, DESPITE THESE DATA, IT HAS NOT BEEN ESTABLISHED WHETHER OXYGEN STRESS INFLUENCES PCOS DEVELOPMENT OR A SECONDARY DISORDER RESULTING FROM HYPERGLYCEMIA, IR, AND CARDIOVASCULAR AND CANCER COMPLICATIONS IN WOMEN.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
16  6713  37 VISCERAL ADIPOSITY SYNDROME. THE ASSOCIATION OF ANTHROPOMETRIC (WAIST CIRCUMFERENCE) AND HEMODYNAMIC (BLOOD PRESSURE) CHANGES WITH ABNORMALITIES IN GLUCOSE AND LIPID METABOLISM HAS BEEN MOTIVATION FOR A LOT OF DISCUSSIONS IN THE LAST 30 YEARS. NOWADAYS, BLOOD PRESSURE, BODY MASS INDEX/ABDOMINAL CIRCUMFERENCE, GLYCEMIA, TRIGLYCERIDEMIA, AND HDL-CHOLESTEROL CONCENTRATIONS ARE CONSIDERED IN THE DEFINITION OF METABOLIC SYNDROME, REFERRED AS VISCERAL ADIPOSITY SYNDROME (VAS) IN THE PRESENT REVIEW. HOWEVER, MORE THAN 250 YEARS AGO AN ASSOCIATION BETWEEN VISCERAL AND MEDIASTINAL OBESITY WITH HYPERTENSION, GOUT, AND OBSTRUCTIVE APNEA HAD ALREADY BEEN RECOGNIZED. EXPANSION OF VISCERAL ADIPOSE TISSUE SECONDARY TO CHRONIC OVER-CONSUMPTION OF CALORIES STIMULATES THE RECRUITMENT OF MACROPHAGES, WHICH ASSUME AN INFLAMMATORY PHENOTYPE AND PRODUCE CYTOKINES THAT DIRECTLY INTERFERE WITH INSULIN SIGNALING, RESULTING IN INSULIN RESISTANCE. IN TURN, INSULIN RESISTANCE (IR) MANIFESTS ITSELF IN VARIOUS TISSUES, CONTRIBUTING TO THE OVERALL PHENOTYPE OF VAS. FOR EXAMPLE, IN WHITE ADIPOSE TISSUE, IR RESULTS IN LIPOLYSIS, INCREASED FREE FATTY ACIDS RELEASE AND WORSENING OF INFLAMMATION, SINCE FATTY ACIDS CAN BIND TO TOLL-LIKE RECEPTORS. IN THE LIVER, IR RESULTS IN INCREASED HEPATIC GLUCOSE PRODUCTION, CONTRIBUTING TO HYPERGLYCEMIA; IN THE VASCULAR ENDOTHELIUM AND KIDNEY, IR RESULTS IN VASOCONSTRICTION, SODIUM RETENTION AND, CONSEQUENTLY, ARTERIAL HYPERTENSION. OTHER PLAYERS HAVE BEEN RECOGNIZED IN THE DEVELOPMENT OF VAS, SUCH AS GENETIC PREDISPOSITION, EPIGENETIC FACTORS ASSOCIATED WITH EXPOSURE TO AN UNFAVOURABLE INTRAUTERINE ENVIRONMENT AND THE GUT MICROBIOTA. MORE RECENTLY, EXPERIMENTAL AND CLINICAL STUDIES HAVE SHOWN THE AUTONOMIC NERVOUS SYSTEM PARTICIPATES IN MODULATING VISCERAL ADIPOSE TISSUE. THE SYMPATHETIC NERVOUS SYSTEM IS RELATED TO ADIPOSE TISSUE FUNCTION AND DIFFERENTIATION THROUGH BETA1, BETA2, BETA3, ALPHA1, AND ALPHA2 ADRENERGIC RECEPTORS. THE RELATION IS BIDIRECTIONAL: SYMPATHETIC DENERVATION OF ADIPOSE TISSUE BLOCKS LIPOLYSIS TO A VARIETY OF LIPOLYTIC STIMULI AND ADIPOSE TISSUE SEND INPUTS TO THE BRAIN. AN IMBALANCE OF SYMPATHETIC/PARASYMPATHETIC AND ALPHA2 ADRENERGIC/BETA3 RECEPTOR IS RELATED TO VISCERAL ADIPOSE TISSUE STORAGE AND INSULIN SENSITIVITY. THUS, IN ADDITION TO THE WELL-KNOWN FACTORS CLASSICALLY ASSOCIATED WITH VAS, ABNORMAL AUTONOMIC ACTIVITY ALSO EMERGES AS AN IMPORTANT FACTOR REGULATING WHITE ADIPOSE TISSUE, WHICH HIGHLIGHTS COMPLEX ROLE OF ADIPOSE TISSUE IN THE VAS.	2016	

17  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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
18  5366  30 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
19  4627  31 NEUROENDOCRINOLOGICAL AND EPIGENETIC MECHANISMS SUBSERVING AUTONOMIC IMBALANCE AND HPA DYSFUNCTION IN THE METABOLIC SYNDROME. IMPACT OF ENVIRONMENTAL STRESS UPON PATHOPHYSIOLOGY OF THE METABOLIC SYNDROME (METS) HAS BEEN SUBSTANTIATED BY EPIDEMIOLOGICAL, PSYCHOPHYSIOLOGICAL, AND ENDOCRINOLOGICAL STUDIES. THIS REVIEW DISCUSSES RECENT ADVANCES IN THE UNDERSTANDING OF CAUSATIVE ROLES OF NUTRITIONAL FACTORS, SYMPATHOMEDULLO-ADRENAL (SMA) AND HYPOTHALAMIC-PITUITARY ADRENOCORTICAL (HPA) AXES, AND ADIPOSE TISSUE CHRONIC LOW-GRADE INFLAMMATION PROCESSES IN METS. DISTURBANCES IN THE NEUROENDOCRINE SYSTEMS FOR LEPTIN, MELANOCORTIN, AND NEUROPEPTIDE Y (NPY)/AGOUTI-RELATED PROTEIN SYSTEMS HAVE BEEN FOUND RESULTING DIRECTLY IN METS-LIKE CONDITIONS. THE REVIEW IDENTIFIES CANDIDATE RISK GENES FROM FACTORS SHOWN CRITICAL FOR THE FUNCTIONING OF EACH OF THESE NEUROENDOCRINE SIGNALING CASCADES. IN ITS META-ANALYTIC PART, RECENT STUDIES IN EPIGENETIC MODIFICATION (HISTONE METHYLATION, ACETYLATION, PHOSPHORYLATION, UBIQUITINATION) AND POSTTRANSCRIPTIONAL GENE REGULATION BY MICRORNAS ARE EVALUATED. SEVERAL STUDIES SUGGEST MODIFICATION MECHANISMS OF EARLY LIFE STRESS (ELS) AND DIET-INDUCED OBESITY (DIO) PROGRAMMING IN THE HYPOTHALAMIC REGIONS WITH POPULATIONS OF POMC-EXPRESSING NEURONS. EPIGENETIC MODIFICATIONS WERE FOUND IN CORTISOL (HERE HSD11B1 EXPRESSION), MELANOCORTIN, LEPTIN, NPY, AND ADIPONECTIN GENES. WITH RESPECT TO ADIPOSITY GENES, EPIGENETIC MODIFICATIONS WERE DOCUMENTED FOR FAT MASS GENE CLUSTER APOA1/C3/A4/A5, AND THE LIPOLYSIS GENE LIPE. WITH REGARD TO INFLAMMATORY, IMMUNE AND SUBCELLULAR METABOLISM, PPARG, NKBF1, TNFA, TCF7C2, AND THOSE GENES EXPRESSING CYTOCHROME P450 FAMILY ENZYMES INVOLVED IN STEROIDOGENESIS AND IN HEPATIC LIPOPROTEINS WERE DOCUMENTED FOR EPIGENETIC MODIFICATIONS.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
20  1098  22 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