1 3118 151 GESTATIONAL DIABETES MELLITUS: GENETIC FACTORS, EPIGENETIC ALTERATIONS, AND MICROBIAL COMPOSITION. GESTATIONAL DIABETES MELLITUS (GDM) IS A COMMON METABOLIC DISORDER, USUALLY DIAGNOSED DURING THE THIRD TRIMESTER OF PREGNANCY THAT USUALLY DISAPPEARS AFTER DELIVERY. IN GDM, THE EXCESS OF GLUCOSE, FATTY ACIDS, AND AMINO ACIDS RESULTS IN FOETUSES LARGE FOR GESTATIONAL AGE. HYPERGLYCAEMIA AND INSULIN RESISTANCE ACCELERATE THE METABOLISM, RAISING THE OXYGEN DEMAND, AND CREATING CHRONIC HYPOXIA AND INFLAMMATION. WOMEN WHO EXPERIENCED GDM AND THEIR OFFSPRING ARE AT RISK OF DEVELOPING TYPE-2 DIABETES, OBESITY, AND OTHER METABOLIC OR CARDIOVASCULAR CONDITIONS LATER IN LIFE. GENETIC FACTORS MAY PREDISPOSE THE DEVELOPMENT OF GDM; HOWEVER, THEY DO NOT ACCOUNT FOR ALL GDM CASES; LIFESTYLE AND DIET ALSO PLAY IMPORTANT ROLES IN GDM DEVELOPMENT BY MODULATING EPIGENETIC SIGNATURES AND THE BODY'S MICROBIAL COMPOSITION; THEREFORE, THIS IS A CONDITION WITH A COMPLEX, MULTIFACTORIAL AETIOLOGY. IN THIS CONTEXT, WE REVISED PUBLISHED REPORTS DESCRIBING GDM-ASSOCIATED SINGLE-NUCLEOTIDE POLYMORPHISMS (SNPS), DNA METHYLATION AND MICRORNA EXPRESSION IN DIFFERENT TISSUES (SUCH AS PLACENTA, UMBILICAL CORD, ADIPOSE TISSUE, AND PERIPHERAL BLOOD), AND MICROBIAL COMPOSITION IN THE GUT, ORAL CAVITY, AND VAGINA FROM PREGNANT WOMEN WITH GDM, AS WELL AS THE BACTERIAL COMPOSITION OF THE OFFSPRING. ALTOGETHER, THESE REPORTS INDICATE THAT A NUMBER OF SNPS ARE ASSOCIATED TO GDM PHENOTYPES AND MAY PREDISPOSE THE DEVELOPMENT OF THE DISEASE. HOWEVER, EXTRINSIC FACTORS (LIFESTYLE, NUTRITION) MODULATE, THROUGH EPIGENETIC MECHANISMS, THE RISK OF DEVELOPING THE DISEASE, AND SOME ASSOCIATION EXISTS BETWEEN THE MICROBIAL COMPOSITION WITH GDM IN AN ORGAN-SPECIFIC MANNER. GENES, EPIGENETIC SIGNATURES, AND MICROBIOTA COULD BE TRANSFERRED TO THE OFFSPRING, INCREASING THE POSSIBILITY OF DEVELOPING CHRONIC DEGENERATIVE CONDITIONS THROUGH POSTNATAL LIFE. 2023 2 6099 46 THE EMERGING ROLE OF BIOMARKERS IN THE DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS. GESTATIONAL DIABETES MELLITUS (GDM) IS A COMMON COMPLICATION OF PREGNANCY; ITS RISING INCIDENCE IS A RESULT OF INCREASED MATERNAL OBESITY AND OLDER MATERNAL AGE TOGETHER WITH ALTERED DIAGNOSTIC CRITERIA IDENTIFYING A GREATER PROPORTION OF PREGNANT WOMEN WITH GDM. ITS CONSEQUENCES ARE FAR-REACHING, ASSOCIATED WITH POORER MATERNAL AND NEONATAL OUTCOMES COMPARED TO NON-GDM PREGNANCIES, AND GDM HAS IMPLICATIONS FOR METABOLIC HEALTH IN BOTH MOTHER AND OFFSPRING. OBJECTIVE MARKERS TO IDENTIFY WOMEN AT HIGH RISK FOR THE DEVELOPMENT OF GDM ARE USEFUL TO TARGET THERAPY AND POTENTIALLY PREVENT ITS DEVELOPMENT. ESTABLISHED CLINICAL RISK FACTORS FOR GDM INCLUDE OVERWEIGHT/OBESITY, AGE, ETHNICITY, AND FAMILY HISTORY OF DIABETES, THOUGH THEY LACK SPECIFICITY FOR ITS DEVELOPMENT. THE ADDITION OF BIOMARKERS TO PREDICTIVE MODELS OF GDM MAY IMPROVE THE ABILITY TO IDENTIFY WOMEN AT RISK OF GDM PRIOR TO ITS DEVELOPMENT. THESE BIOMARKERS REFLECT THE PATHOPHYSIOLOGIC MECHANISMS OF GDM INVOLVING INSULIN RESISTANCE, CHRONIC INFLAMMATION, AND ALTERED PLACENTAL FUNCTION. IN ADDITION, THE ROLE OF EPIGENETIC CHANGES IN GDM PATHOGENESIS HIGHLIGHTS THE COMPLEX INTERPLAY BETWEEN GENETIC AND ENVIRONMENTAL FACTORS, POTENTIALLY OFFERING FURTHER REFINEMENT OF THE PREDICTION OF GDM RISK. IN THIS REVIEW, WE WILL DISCUSS THE CLINICAL CHALLENGES ASSOCIATED WITH THE DIAGNOSIS OF GDM AND ITS CURRENT PATHOPHYSIOLOGIC BASIS, GIVING RISE TO POTENTIAL BIOMARKERS THAT MAY AID IN ITS IDENTIFICATION. WHILE NOT YET VALIDATED FOR CLINICAL USE, WE EXPLORE THE POSSIBLE CLINICAL ROLE OF BIOMARKERS IN THE FUTURE. WE ALSO EXPLORE NOVEL DIAGNOSTIC TOOLS, INCLUDING HIGH THROUGHPUT METHODOLOGIES, THAT MAY HAVE POTENTIAL FUTURE APPLICATION IN THE IDENTIFICATION OF WOMEN WITH GDM. 2018 3 6279 50 THE PLACENTA AS A TARGET OF EPIGENETIC ALTERATIONS IN WOMEN WITH GESTATIONAL DIABETES MELLITUS AND POTENTIAL IMPLICATIONS FOR THE OFFSPRING. GESTATIONAL DIABETES MELLITUS (GDM) IS A PREGNANCY COMPLICATION FIRST DETECTED IN THE SECOND OR THIRD TRIMESTER IN WOMEN THAT DID NOT SHOW EVIDENT GLUCOSE INTOLERANCE OR DIABETES BEFORE GESTATION. IN 2019, THE INTERNATIONAL DIABETES FEDERATION REPORTED THAT 15.8% OF LIVE BIRTHS WERE AFFECTED BY HYPERGLYCEMIA DURING PREGNANCY, OF WHICH 83.6% WERE DUE TO GESTATIONAL DIABETES MELLITUS, 8.5% WERE DUE TO DIABETES FIRST DETECTED IN PREGNANCY, AND 7.9% WERE DUE TO DIABETES DETECTED BEFORE PREGNANCY. GDM INCREASES THE SUSCEPTIBILITY TO DEVELOPING CHRONIC DISEASES FOR BOTH THE MOTHER AND THE BABY LATER IN LIFE. UNDER GDM CONDITIONS, THE INTRAUTERINE ENVIRONMENT BECOMES HYPERGLYCEMIC, WHILE ALSO SHOWING HIGH CONCENTRATIONS OF FATTY ACIDS AND PROINFLAMMATORY CYTOKINES, PRODUCING MORPHOLOGICAL, STRUCTURAL, AND MOLECULAR MODIFICATIONS IN THE PLACENTA, AFFECTING ITS FUNCTION; THESE ALTERATIONS MAY PREDISPOSE THE BABY TO DISEASE IN ADULT LIFE. MOLECULAR ALTERATIONS INCLUDE EPIGENETIC MECHANISMS SUCH AS DNA AND RNA METHYLATION, CHROMATIN REMODELING, HISTONE MODIFICATIONS, AND EXPRESSION OF NONCODING RNAS (NCRNAS). THE PLACENTA IS A UNIQUE ORGAN THAT ORIGINATES ONLY IN PREGNANCY, AND ITS MAIN FUNCTION IS COMMUNICATION BETWEEN THE MOTHER AND THE FETUS, ENSURING HEALTHY DEVELOPMENT. THUS, THIS REVIEW PROVIDES UP-TO-DATE INFORMATION REGARDING TWO OF THE BEST-DOCUMENTED (EPIGENETIC) MECHANISMS (DNA METHYLATION AND MIRNA EXPRESSION) ALTERED IN THE HUMAN PLACENTA UNDER GDM CONDITIONS, AS WELL AS POTENTIAL IMPLICATIONS FOR THE OFFSPRING. 2021 4 4782 41 NUTRIGENETICS, EPIGENETICS AND GESTATIONAL DIABETES: CONSEQUENCES IN MOTHER AND CHILD. GESTATIONAL DIABETES MELLITUS (GDM) IS THE MOST COMMON METABOLIC CONDITION DURING PREGNANCY AND MAY RESULT IN SHORT- AND LONG-TERM COMPLICATIONS FOR BOTH MOTHER AND OFFSPRING. THE COMPLEXITY OF PHENOTYPIC OUTCOMES SEEMS INFLUENCED BY GENETIC SUSCEPTIBILITY, NUTRIENT-GENE INTERACTIONS AND LIFESTYLE INTERACTING WITH CLINICAL FACTORS. THERE IS STRONG EVIDENCE THAT NOT ONLY THE ADVERSE GENETIC BACKGROUND BUT ALSO THE EPIGENETIC MODIFICATIONS IN RESPONSE TO NUTRITIONAL AND ENVIRONMENTAL FACTORS COULD INFLUENCE THE MATERNAL HYPERGLYCEMIA IN PREGNANCY AND THE FOETAL METABOLIC PROGRAMMING. IN THIS VIEW, THE CORRELATION BETWEEN EPIGENETIC MODIFICATIONS AND THEIR TRANSGENERATIONAL EFFECTS REPRESENTS A VERY INTERESTING FIELD OF STUDY. THE PRESENT REVIEW GIVES INSIGHT INTO THE ROLE OF GENE VARIANTS AND THEIR INTERACTIONS WITH NUTRIENTS IN GDM. IN ADDITION, WE PROVIDE AN OVERVIEW OF THE EPIGENETIC CHANGES AND THEIR ROLE IN THE MATERNAL-FOETAL TRANSMISSION OF CHRONIC DISEASES. OVERALL, THE KNOWLEDGE OF EPIGENETIC MODIFICATIONS INDUCED BY AN ADVERSE INTRAUTERINE AND PERINATAL ENVIRONMENT COULD SHED LIGHT ON THE POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS OF LONG-TERM DISEASE DEVELOPMENT IN THE OFFSPRING AND PROVIDE USEFUL TOOLS FOR THEIR PREVENTION. 2019 5 6861 41 [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 6 3707 39 INFLUENCE OF MATERNAL OVERNUTRITION AND GESTATIONAL DIABETES ON THE PROGRAMMING OF METABOLIC HEALTH OUTCOMES IN THE OFFSPRING: EXPERIMENTAL EVIDENCE. THE INCIDENCE OF OBESITY AND TYPE 2 DIABETES MELLITUS HAVE RISEN ACROSS THE WORLD DURING THE PAST FEW DECADES AND HAS ALSO REACHED AN ALARMING LEVEL AMONG CHILDREN. IN ADDITION, WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. AS A RESULT, THE INCIDENCE OF GESTATIONAL DIABETES MELLITUS IS ALSO ON THE RISE. WHILE DIET AND LIFESTYLE CONTRIBUTE TO THESE TRENDS, POPULATION HEALTH DATA SHOW THAT MATERNAL OBESITY AND DIABETES DURING PREGNANCY DURING CRITICAL STAGES OF DEVELOPMENT ARE MAJOR FACTORS THAT CONTRIBUTE TO THE DEVELOPMENT OF CHRONIC DISEASE IN ADOLESCENT AND ADULT OFFSPRING. FETAL PROGRAMMING OF METABOLIC FUNCTION, THROUGH PHYSIOLOGICAL AND (OR) EPIGENETIC MECHANISMS, MAY ALSO HAVE AN INTERGENERATIONAL EFFECT, AND AS A RESULT MAY PERPETUATE METABOLIC DISORDERS IN THE NEXT GENERATION. IN THIS REVIEW, WE SUMMARIZE THE EXISTING LITERATURE THAT CHARACTERIZES HOW MATERNAL OBESITY AND GESTATIONAL DIABETES MELLITUS CONTRIBUTE TO METABOLIC AND CARDIOVASCULAR DISORDERS IN THE OFFSPRING. IN PARTICULAR, WE FOCUS ON ANIMAL STUDIES THAT INVESTIGATE THE MOLECULAR MECHANISMS THAT ARE PROGRAMMED BY THE GESTATIONAL ENVIRONMENT AND LEAD TO DISEASE PHENOTYPES IN THE OFFSPRING. WE ALSO REVIEW INTERVENTIONAL STUDIES THAT PREVENT DISEASE WITH A DEVELOPMENTAL ORIGIN IN THE OFFSPRING. 2015 7 4087 42 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 8 2267 39 EPIGENETIC PROGRAMMING OF OBESITY AND DIABETES BY IN UTERO EXPOSURE TO GESTATIONAL DIABETES MELLITUS. IT IS NOW WELL ACCEPTED THAT OFFSPRING EXPOSED TO MATERNAL UNDERNUTRITION, OBESITY, OR GESTATIONAL DIABETES MELLITUS HAVE AN INCREASED RISK FOR CHRONIC DISEASES LATER IN LIFE, SUPPORTING THE THEORY OF THE EARLY ORIGINS OF CHRONIC DISEASES. HOWEVER, THE MOLECULAR MECHANISMS THROUGH WHICH THE EXPOSURE TO AN ALTERED IN UTERO ENVIRONMENT TRANSLATES INTO THE DEVELOPMENT OF CHRONIC DISEASES ARE NOT YET WELL UNDERSTOOD. RECENTLY REPORTED PROMISING RESULTS HELP TO RESOLVE THIS ISSUE. THEY SUGGEST THAT EPIGENETIC MODIFICATIONS ARE A POTENTIAL MECHANISM FOR FETAL METABOLIC PROGRAMMING. THIS REVIEW PROVIDES AN OVERVIEW OF THE RELATIONSHIP BETWEEN THE EXPOSURE TO AN ALTERED INTRAUTERINE ENVIRONMENT AND FETAL METABOLIC PROGRAMMING, FOCUSING ON GESTATIONAL DIABETES MELLITUS AND EPIGENETIC VARIATIONS AT ADIPOKINE CANDIDATE GENES. 2013 9 4802 37 OBESITY AND LIFESPAN HEALTH--IMPORTANCE OF THE FETAL ENVIRONMENT. A MARKED INCREASE IN THE FREQUENCY OF OBESITY AT THE POPULATION LEVEL HAS RESULTED IN AN INCREASING NUMBER OF OBESE WOMEN ENTERING PREGNANCY. THE INCREASING REALIZATION OF THE IMPORTANCE OF THE FETAL ENVIRONMENT IN RELATION TO CHRONIC DISEASE ACROSS THE LIFESPAN HAS FOCUSED ATTENTION ON THE ROLE OF MATERNAL OBESITY IN FETAL DEVELOPMENT. PREVIOUS STUDIES HAVE DEMONSTRATED THAT OBESITY DURING ADOLESCENCE AND ADULTHOOD CAN BE TRACED BACK TO FETAL AND EARLY CHILDHOOD EXPOSURES. THIS REVIEW FOCUSES ON FACTORS THAT CONTRIBUTE TO EARLY DEVELOPMENTAL EVENTS, SUCH AS EPIGENETIC MODIFICATIONS, THE POTENTIAL FOR AN INCREASE IN INFLAMMATORY BURDEN, EARLY DEVELOPMENTAL PROGRAMMING CHANGES SUCH AS THE VARIABLE DEVELOPMENT OF WHITE VERSUS BROWN ADIPOSE TISSUE, AND ALTERATIONS IN ORGAN ONTOGENY. WE HYPOTHESIZE THAT THESE MECHANISMS PROMOTE AN UNFAVORABLE FETAL ENVIRONMENT AND CAN HAVE A LONG-STANDING IMPACT, WITH EARLY MANIFESTATIONS OF CHRONIC DISEASE THAT CAN RESULT IN AN INCREASED DEMAND FOR FUTURE HEALTH CARE. IN ORDER TO IDENTIFY APPROPRIATE PREVENTIVE MEASURES, ATTENTION NEEDS TO BE PLACED BOTH ON REDUCING MATERNAL OBESITY AS WELL AS UNDERSTANDING THE MOLECULAR, CELLULAR, AND EPIGENETIC MECHANISMS THAT MAY BE RESPONSIBLE FOR THE PRENATAL ONSET OF CHRONIC DISEASE. 2014 10 3572 43 IMPACT OF MATERNAL DIABETES ON EPIGENETIC MODIFICATIONS LEADING TO DISEASES IN THE OFFSPRING. GESTATIONAL DIABETES, OCCURRING DURING THE HYPERGLYCEMIC PERIOD OF PREGNANCY IN MATERNAL LIFE, IS A PATHOLOGIC STATE THAT INCREASES THE INCIDENCE OF COMPLICATIONS IN BOTH MOTHER AND FETUS. OFFSPRING THUS EXPOSED TO AN ADVERSE FETAL AND EARLY POSTNATAL ENVIRONMENT MAY MANIFEST INCREASED SUSCEPTIBILITY TO A NUMBER OF CHRONIC DISEASES LATER IN LIFE. COMPELLING EVIDENCE FOR THE ROLE OF EPIGENETIC TRANSMISSION IN THESE COMPLICATIONS HAS COME FROM COMPARISON OF SIBLINGS BORN BEFORE AND AFTER THE DEVELOPMENT OF MATERNAL DIABETES, EXPOSURE TO THIS INTRAUTERINE DIABETIC ENVIRONMENT BEING SHOWN TO CAUSE ALTERATIONS IN FETAL GROWTH PATTERNS WHICH PREDISPOSE THESE INFANTS TO DEVELOPING OVERWEIGHT AND OBESITY LATER IN LIFE. DIABETES OF THE OFFSPRING IS ALSO MAINLY THE CONSEQUENCE OF EXPOSURE TO THE DIABETIC INTRAUTERINE ENVIRONMENT, IN ADDITION TO GENETIC SUSCEPTIBILITY. SINCE OBESITY AND DIABETES ARE KNOWN TO INCREASE THE RISK OF CARDIOVASCULAR DISEASE, CARDIOVASCULAR SEQUELAE IN THE OFFSPRING OF DIABETIC MOTHERS ARE VIRTUALLY INEVITABLE. RESEARCH DATA ALSO SUGGEST THAT EXPOSURE TO A DIABETIC INTRAUTERINE ENVIRONMENT DURING PREGNANCY IS ASSOCIATED WITH AN INCREASE IN DYSLIPIDEMIA, SUBCLINICAL VASCULAR INFLAMMATION, AND ENDOTHELIAL DYSFUNCTION PROCESSES IN THE OFFSPRING, ALL OF WHICH ARE LINKED WITH DEVELOPMENT OF CARDIOVASCULAR DISEASE LATER IN LIFE. THE MAIN UNDERLYING MECHANISMS INVOLVE PERSISTENT HYPERGLYCEMIA HYPERINSULINEMIA AND LEPTIN RESISTANCE. 2012 11 1376 38 DEVELOPMENTAL PROGRAMMING OF BODY COMPOSITION: UPDATE ON EVIDENCE AND MECHANISMS. PURPOSE OF REVIEW: A GROWING BODY OF EPIDEMIOLOGICAL AND EXPERIMENTAL DATA INDICATE THAT NUTRITIONAL OR ENVIRONMENTAL STRESSORS DURING EARLY DEVELOPMENT CAN INDUCE LONG-TERM ADAPTATIONS THAT INCREASE RISK OF OBESITY, DIABETES, CARDIOVASCULAR DISEASE, AND OTHER CHRONIC CONDITIONS-A PHENOMENON TERMED "DEVELOPMENTAL PROGRAMMING." A COMMON PHENOTYPE IN HUMANS AND ANIMAL MODELS IS ALTERED BODY COMPOSITION, WITH REDUCED MUSCLE AND BONE MASS, AND INCREASED FAT MASS. IN THIS REVIEW, WE SUMMARIZE THE RECENT LITERATURE LINKING PRENATAL FACTORS TO FUTURE BODY COMPOSITION AND EXPLORE CONTRIBUTING MECHANISMS. RECENT FINDINGS: MANY PRENATAL EXPOSURES, INCLUDING INTRAUTERINE GROWTH RESTRICTION, EXTREMES OF BIRTH WEIGHT, MATERNAL OBESITY, AND MATERNAL DIABETES, ARE ASSOCIATED WITH INCREASED FAT MASS, REDUCED MUSCLE MASS, AND DECREASED BONE DENSITY, WITH EFFECTS REPORTED THROUGHOUT INFANCY AND CHILDHOOD, AND PERSISTING INTO MIDDLE AGE. MECHANISMS AND MEDIATORS INCLUDE MATERNAL DIET, BREASTMILK COMPOSITION, METABOLITES, APPETITE REGULATION, GENETIC AND EPIGENETIC INFLUENCES, STEM CELL COMMITMENT AND FUNCTION, AND MITOCHONDRIAL METABOLISM. DIFFERENCES IN BODY COMPOSITION ARE A COMMON PHENOTYPE FOLLOWING DISRUPTIONS TO THE PRENATAL ENVIRONMENT, AND MAY CONTRIBUTE TO DEVELOPMENTAL PROGRAMMING OF OBESITY AND DIABETES RISK. 2019 12 4972 35 PATHOPHYSIOLOGICAL BASIS FOR COMPROMISED HEALTH BEYOND GENERATIONS: ROLE OF MATERNAL HIGH-FAT DIET AND LOW-GRADE CHRONIC INFLAMMATION. EARLY EXPOSURE TO A FAT-ENRICHED DIET PROGRAMS THE DEVELOPMENTAL PROFILE AND THUS IS ASSOCIATED WITH DISEASE SUSCEPTIBILITY IN SUBSEQUENT GENERATIONS. CHRONIC LOW-GRADE INFLAMMATION, RESULTING FROM MATERNAL HIGH-FAT DIET, IS ACTIVATED IN THE FETAL ENVIRONMENT AND IN MANY ORGANS OF OFFSPRING, INCLUDING PLACENTA, ADIPOSE, LIVER, VASCULAR SYSTEM AND BRAIN. THE PREVALENCE OF AN INFLAMMATORY RESPONSE IS HIGHLY ASSOCIATED WITH OBESITY INCIDENCE, CARDIOVASCULAR DISEASES, NONALCOHOLIC FATTY LIVER DISEASE AND BRAIN DAMAGE. SUBSTANTIAL STUDIES USING HIGH-FAT MODEL HAVE CONSISTENTLY DEMONSTRATED THE INCIDENCE OF SUCH INFLAMMATORY REACTIONS; HOWEVER, THE POTENTIAL CONTRIBUTION OF ACTIVE INFLAMMATION TOWARD THE PHYSIOLOGICAL OUTCOMES AND DEVELOPMENTAL DISEASES IS NEITHER DISCUSSED IN DEPTH NOR SYSTEMICALLY INTEGRATED. THEREFORE, WE AIM TO SUMMARIZE THE CURRENT FINDINGS IN REGARDS TO HOW A MATERNAL HIGH-FAT DIET INFLUENCES THE INFLAMMATORY STATUS, AND PROBABLE PATHOGENIC EFFECTS ON THE OFFSPRING. MORE IMPORTANTLY, SINCE LIMITED RESEARCH HAS BEEN CONDUCTED TO REVEAL THE EPIGENETIC REGULATION OF THESE INFLAMMATORY MARKERS BY MATERNAL HIGH-FAT DIET, WE SINCERELY HOPE THAT OUR REVIEW WILL NOT ONLY OUTLINE THE PATHOPHYSIOLOGICAL RELEVANCE OF INFLAMMATION BUT ALSO IDENTIFY A FUTURE DIRECTION FOR MECHANISTIC INVESTIGATION AND CLINICAL APPLICATION. 2015 13 44 40 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 14 6819 34 [FETAL PROGRAMMING OF METABOLIC DISORDERS]. OUR KNOWLEDGE OF FETAL PROGRAMMING HAS DEVELOPED NOTABLY OVER THE YEARS AND RECENT DATA SUGGEST THAT AN UNBALANCED DIET PRIOR AND DURING PREGNANCY CAN HAVE EARLY-ONSET AND LONG-LASTING CONSEQUENCES ON THE HEALTH OF THE OFFSPRING. SPECIFIC NEGATIVE INFLUENCES OF HIGH DIETARY GLUCOSE AND LIPID CONSUMPTION, AS WELL AS UNDERNUTRITION, ARE ASSOCIATED WITH DEVELOPMENT OF METABOLIC SYNDROME, INSULIN RESISTANCE AND DIABETES IN THE OFFSPRING. THE MECHANISMS UNDERLYING THE EFFECTS OF MATERNAL HYPERGLYCEMIA ON THE FETUS MAY INVOLVE STRUCTURAL, METABOLIC AND EPIGENETIC CHANGES. THE AIM OF THIS REVIEW IS TO ILLUSTRATE HOW ADVERSE INTRAUTERINE ENVIRONMENT MAY INFLUENCE MOLECULAR MODIFICATIONS IN THE FETUS AND CAUSE EPIGENETIC ALTERATIONS IN PARTICULAR. IT HAS BEEN DEMONSTRATED THAT PRENATAL EPIGENETIC MODIFICATIONS MAY BE LINKED TO THE PATHOGENESIS AND PROGRESSION OF THE ADULT CHRONIC DISORDERS. STUDIES ON EPIGENETIC ALTERATIONS WILL CONTRIBUTE TO A BETTER UNDERSTANDING OF THE LONG-TERM EFFECTS OF IN UTERO EXPOSURE AND MAY OPEN NEW PERSPECTIVES FOR DISEASE PREVENTION AND TREATMENT. 2015 15 2038 21 EPIGENETIC CHANGES PREDISPOSING TO TYPE 2 DIABETES IN INTRAUTERINE GROWTH RETARDATION. EPIDEMIOLOGIC STUDIES HAVE DEMONSTRATED AN ASSOCIATION BETWEEN INTRAUTERINE GROWTH RETARDATION AND A GREATER RISK OF CHRONIC DISEASE, INCLUDING CORONARY HEART DISEASE, HYPERTENSION, STROKE, AND TYPE 2 DIABETES IN ADULTHOOD. AN ADVERSE INTRAUTERINE ENVIRONMENT MAY AFFECT BOTH GROWTH AND DEVELOPMENT OF THE ORGANISM, PERMANENTLY PROGRAMMING ENDOCRINE AND METABOLIC FUNCTIONS. ONE OF THE MECHANISMS OF PROGRAMMING IS THE EPIGENETIC MODIFICATION OF GENE PROMOTERS INVOLVED IN THE CONTROL OF KEY METABOLIC PATHWAYS. THE AIM OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF THE EXPERIMENTAL EVIDENCE SHOWING THE EFFECTS OF EARLY EXPOSURE TO SUBOPTIMAL ENVIRONMENT ON EPIGENOME. THE KNOWLEDGE OF THE EPIGENETIC MARKERS OF PROGRAMMING MAY ALLOW THE IDENTIFICATION OF SUSCEPTIBLE INDIVIDUALS AND THE DESIGN OF TARGETED PREVENTION STRATEGIES. 2010 16 6873 43 [PREVENTION OF OBESITY FROM PERINATAL STAGE]. OBESITY IS ONE OF THE MAJOR HEALTH PROBLEMS AND A DETERMINING FACTOR IN THE PREVALENCE OF DISEASES SUCH AS METABOLIC SYNDROME, ASTHMA, SLEEP APNEA, INFERTILITY AND VARIOUS TYPES OF CANCER. ITS ORIGIN IS MULTIFACTORIAL, INVOLVING GENETIC, SOCIOECONOMIC AND ENVIRONMENTAL FACTORS. THESE LAST ONES CONTRIBUTE MOSTLY TO EXPLAIN THE CURRENT EPIDEMIC GROWTH OF THIS DISEASE. THE SEDENTARY LIFESTYLE, INADEQUATE DIET, LACK OF SLEEP, ALTERATIONS IN INTESTINAL MICROBIOTA AND STRESS ARE FACTORS RELATED TO ITS DEVELOPMENT. SINCE BARKER PRESENTED HIS HYPOTHESIS ABOUT THE "FETAL ORIGIN OF ADULT DISEASES", THERE ARE INCREASING NUMBER OF STUDIES THAT SHOW THE INFLUENCE OF AN INADEQUATE NUTRITIONAL STATUS AND MATERNAL WEIGHT IN THE DEVELOPMENT OF CHRONIC DISEASES, AS OBESITY IN OFFSPRING. THE NUTRITIONAL DEFICIENCIES OF THE PREGNANT MOTHER CAUSE EPIGENETIC MODIFICATIONS AND ABNORMAL PROGRAMMING OF THE DEVELOPMENT OFORGANS AND DEVICES, ADAPTING THE FETUS TO THIS SITUATION OF DEFICIENCY AND BEING ABLE TO ADAPT TO AN OBESOGENIC ENVIRONMENT AFTER BIRTH, INCREASING ITS PROPENSITY TO OBESITY. ALSO, POOR MATERNAL NUTRITIONAL STATUS IS RELATED TO INTRAUTERINE GROWTH RETARDATION AND LOW BIRTH WEIGHT INFANTS, WITH A HIGHER RISK OF CHILDHOOD AND ADULT CENTRAL OBESITY. CURRENTLY, DEFICIENT INTAKE OF MICRONUTRIENTS AND OVERWEIGHT OR MATERNAL OBESITY TEND TO OVERLAP, AND THIS COMBINATION MAY EXACERBATE THE INCREASE IN OBESITY IN THE OFFSPRING. IT IS IMPORTANT TO IDENTIFY PREGNANT MOTHERS AT RISK OF SUFFERING NUTRITIONAL ALTERATIONS AND ESTABLISH THEIR IMPROVEMENT AS A PRIMARY PREVENTION STRATEGY FOR OVERWEIGHT AND OBESITY. 2017 17 6380 41 THE ROLE OF OBESITY AND DIABETES IN DEMENTIA. CHRONIC CONDITIONS SUCH AS OBESITY, DIABETES, AND DEMENTIA ARE INCREASING IN THE UNITED STATES (US) POPULATION. KNOWLEDGE OF THESE CHRONIC CONDITIONS, PREVENTATIVE MEASURES, AND PROPER MANAGEMENT TACTICS IS IMPORTANT AND CRITICAL TO PREVENTING DISEASE. THE OVERLAP BETWEEN OBESITY, DIABETES, AND DEMENTIA IS BECOMING FURTHER ELUCIDATED. THESE CONDITIONS SHARE A SIMILAR ORIGIN THROUGH THE COMPONENTS OF INCREASING AGE, GENDER, GENETIC AND EPIGENETIC PREDISPOSITIONS, DEPRESSION, AND A HIGH-FAT WESTERN DIET (WD) THAT ALL CONTRIBUTE TO THE INFLAMMATORY STATE ASSOCIATED WITH THE DEVELOPMENT OF OBESITY, DIABETES, AND DEMENTIA. THIS INFLAMMATORY STATE LEADS TO THE DYSREGULATION OF FOOD INTAKE AND INSULIN RESISTANCE. OBESITY IS OFTEN THE CORNERSTONE THAT LEADS TO THE DEVELOPMENT OF DIABETES AND, SUBSEQUENTLY, IN THE CASE OF TYPE 2 DIABETES MELLITUS (T2DM), PROGRESSION TO "TYPE 3 DIABETES MELLITUS (T3DM)". OBESITY AND DEPRESSION ARE CLOSELY ASSOCIATED WITH DIABETES. HOWEVER, DEMENTIA CAN BE AVOIDED WITH LIFESTYLE MODIFICATIONS, BY SWITCHING TO A PLANT-BASED DIET (E.G., A MEDITERRANEAN DIET (MD)), AND INCREASING PHYSICAL ACTIVITY. DIET AND EXERCISE ARE NOT THE ONLY TREATMENT OPTIONS. THERE ARE SEVERAL SURGICAL AND PHARMACOLOGICAL INTERVENTIONS AVAILABLE FOR PREVENTION. CURRENT AND FUTURE RESEARCH WITHIN EACH OF THESE FIELDS IS WARRANTED AND OFFERS THE CHANCE FOR NEW TREATMENT OPTIONS AND A BETTER UNDERSTANDING OF THE PATHOGENESIS OF EACH CONDITION. 2022 18 4662 42 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 19 6557 37 TRANSGENERATIONAL EPIGENETIC INHERITANCE OF DIABETES RISK AS A CONSEQUENCE OF EARLY NUTRITIONAL IMBALANCES. IN TODAY'S WORLD, THERE IS AN UNPRECEDENTED RISE IN THE PREVALENCE OF CHRONIC METABOLIC DISEASES, INCLUDING OBESITY, INSULIN RESISTANCE AND TYPE 2 DIABETES (T2D). THE PATHOGENESIS OF T2D INCLUDES BOTH GENETIC AND ENVIRONMENTAL FACTORS, SUCH AS EXCESSIVE ENERGY INTAKE AND PHYSICAL INACTIVITY. IT HAS RECENTLY BEEN SUGGESTED THAT ENVIRONMENTAL FACTORS EXPERIENCED DURING EARLY STAGES OF DEVELOPMENT, INCLUDING THE INTRAUTERINE AND NEONATAL PERIODS, MIGHT PLAY A MAJOR ROLE IN PREDISPOSING INDIVIDUALS TO T2D. FURTHERMORE, SEVERAL STUDIES HAVE SHOWN THAT SUCH EARLY ENVIRONMENTAL CONDITIONS MIGHT EVEN CONTRIBUTE TO DISEASE RISK IN FURTHER GENERATIONS. IN THIS REVIEW, WE SUMMARISE RECENT DATA DESCRIBING HOW PARENTAL NUTRITION DURING DEVELOPMENT INCREASES THE RISK OF DIABETES IN THE OFFSPRING. WE ALSO DISCUSS THE POTENTIAL MECHANISMS UNDERLYING TRANSGENERATIONAL INHERITANCE OF METABOLIC DISEASE, WITH PARTICULAR EMPHASIS ON EPIGENETIC MECHANISMS. 2016 20 140 34 ABERRANT DNA METHYLATION MEDIATES THE TRANSGENERATIONAL RISK OF METABOLIC AND CHRONIC DISEASE DUE TO MATERNAL OBESITY AND OVERNUTRITION. MATERNAL OBESITY IS A RAPIDLY EVOLVING UNIVERSAL EPIDEMIC LEADING TO ACUTE AND LONG-TERM MEDICAL AND OBSTETRIC HEALTH ISSUES, INCLUDING INCREASED MATERNAL RISKS OF GESTATIONAL DIABETES, HYPERTENSION AND PRE-ECLAMPSIA, AND THE FUTURE RISKS FOR OFFSPRING'S PREDISPOSITION TO METABOLIC DISEASES. EPIGENETIC MODIFICATION, IN PARTICULAR DNA METHYLATION, REPRESENTS A MECHANISM WHEREBY ENVIRONMENTAL EFFECTS IMPACT ON THE PHENOTYPIC EXPRESSION OF HUMAN DISEASE. MATERNAL OBESITY OR OVERNUTRITION CONTRIBUTES TO THE ALTERATIONS IN DNA METHYLATION DURING EARLY LIFE WHICH, THROUGH FETAL PROGRAMMING, CAN PREDISPOSE THE OFFSPRING TO MANY METABOLIC AND CHRONIC DISEASES, SUCH AS NON-ALCOHOLIC FATTY LIVER DISEASE, OBESITY, DIABETES, AND CHRONIC KIDNEY DISEASE. THIS REVIEW AIMS TO SUMMARIZE FINDINGS FROM HUMAN AND ANIMAL STUDIES, WHICH SUPPORT THE ROLE OF MATERNAL OBESITY IN FETAL PROGRAMING AND THE POTENTIAL BENEFIT OF ALTERING DNA METHYLATION TO LIMIT MATERNAL OBESITY RELATED DISEASE IN THE OFFSPRING. 2021