1 5584 98 ROLE OF OBESITY IN FEMALE REPRODUCTION. CONTEMPORARY SCIENTISTS NEED NO "P VALUE" AND "RELATIVE RISK" STATISTICS TO BE EXQUISITELY AWARE OF THE INCREASING PREVALENCE OF OBESITY AND COMPLICATIONS POSED BY OBESITY. IT IS NOW WELL RECOGNIZED THAT OBESITY IS STRONGLY ASSOCIATED WITH TYPE 2 DIABETES, HYPERTENSION, VASCULAR DISEASE, TUMORS AND REPRODUCTIVE DISORDERS. OBESE WOMEN SHOW LOWER LEVELS OF GONADOTROPIN HORMONES, REDUCED FECUNDITY, HIGHER MISCARRIAGE RATES AND POORER OUTCOMES OF IN VITRO FERTILIZATION, REVEALING THAT OBESITY AFFECTS FEMALE REPRODUCTION. IN ADDITION, ADIPOSE TISSUE CONTAINS SPECIAL IMMUNE CELLS AND OBESITY-INDUCED INFLAMMATION IS A CHRONIC, LOW-GRADE INFLAMMATORY RESPONSE. HEREIN, WE MAINLY REVIEW DETRIMENTAL INFLUENCES OF OBESITY IN THE COMPLETE PROCESS OF FEMALE REPRODUCTION, INCLUDING HYPOTHALAMIC-PITUITARY-OVARIAN AXIS, OOCYTE MATURATION, EMBRYO AND FETAL DEVELOPMENT. IN THE LATTER PART, WE VIEW OBESITY-INDUCED INFLAMMATION AND DISCUSS RELATED EPIGENETIC IMPACT ON FEMALE REPRODUCTION. 2023 2 4803 24 OBESITY AND MALE INFERTILITY. THE WORLDWIDE PREVALENCE OF OBESITY IS INCREASING AMONG BOTH SEXES, WITH ASSOCIATED IMPACTS ON CHRONIC HEALTH AND MEDICAL COMORBIDITIES. SIMILARLY, THE EFFECTS OF OBESITY ON REPRODUCTIVE HEALTH ARE INCREASINGLY BEING RECOGNIZED. ADIPOSITY IS ASSOCIATED WITH REDUCED FERTILITY IN MEN, WITH A COMPLEX AND MULTIFACTORIAL ETIOLOGY. THE REPORTED EFFECTS OF OBESITY ON SEMEN PARAMETERS AND IMPAIRED FERTILITY ARE CONTRASTING, WITH SOME STUDIES SHOWING A CLEAR REDUCTION IN REPRODUCTIVE OUTCOMES ASSOCIATED WITH INCREASED BODY MASS INDEX, WHILE OTHERS DO NOT SHOW SUCH IMPACTS. THESE CONTROVERSIES MAY BE DUE TO THE COMPLEX PATHOPHYSIOLOGY AND INTERPLAY BETWEEN GONADOTROPINS AND END ORGANS, AS WELL AS GENETIC AND EPIGENETIC CHANGES AND OXIDATIVE STRESS ON MALE FERTILITY AND FUNCTION. THESE DIFFERENT ASPECTS HAVE LED TO HETEROGENEOUS PARTICIPANTS IN STUDIES AND VARYING IMPLICATIONS FOR ASSISTED REPRODUCTIVE OUTCOMES AS WELL AS OFFSPRING HEALTH. TREATMENT MODALITIES TO MANAGE OBESITY INCLUDE LIFESTYLE, MEDICAL, AND SURGICAL OPTIONS, WITH EMERGING AND EFFECTIVE MEDICAL TREATMENTS SHOWING PROMISE IN REPRODUCTIVE OUTCOMES. 2023 3 4804 30 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 4 6426 25 THE TRANSGENERATIONAL TRANSMISSION OF THE PATERNAL TYPE 2 DIABETES-INDUCED SUBFERTILITY PHENOTYPE. DIABETES IS A CHRONIC METABOLIC DISORDER CHARACTERIZED BY HYPERGLYCEMIA AND ASSOCIATED WITH MANY HEALTH COMPLICATIONS DUE TO THE LONG-TERM DAMAGE AND DYSFUNCTION OF VARIOUS ORGANS. A CONSEQUENTIAL COMPLICATION OF DIABETES IN MEN IS REPRODUCTIVE DYSFUNCTION, REDUCED FERTILITY, AND POOR REPRODUCTIVE OUTCOMES. HOWEVER, THE MOLECULAR MECHANISMS RESPONSIBLE FOR DIABETIC ENVIRONMENT-INDUCED SPERM DAMAGE AND OVERALL DECREASED REPRODUCTIVE OUTCOMES ARE NOT FULLY ESTABLISHED. WE EVALUATED THE EFFECTS OF TYPE 2 DIABETES EXPOSURE ON THE REPRODUCTIVE SYSTEM AND THE REPRODUCTIVE OUTCOMES OF MALES AND THEIR MALE OFFSPRING, USING A MOUSE MODEL. WE DEMONSTRATE THAT PATERNAL EXPOSURE TO TYPE 2 DIABETES MEDIATES INTERGENERATIONAL AND TRANSGENERATIONAL EFFECTS ON THE REPRODUCTIVE HEALTH OF THE OFFSPRING, ESPECIALLY ON SPERM QUALITY, AND ON METABOLIC CHARACTERISTICS. GIVEN THE TRANSGENERATIONAL IMPAIRMENT OF REPRODUCTIVE AND METABOLIC PARAMETERS THROUGH TWO GENERATIONS, THESE CHANGES LIKELY TAKE THE FORM OF INHERITED EPIGENETIC MARKS THROUGH THE GERMLINE. OUR RESULTS EMPHASIZE THE IMPORTANCE OF IMPROVING METABOLIC HEALTH NOT ONLY IN WOMEN OF REPRODUCTIVE AGE, BUT ALSO IN POTENTIAL FATHERS, IN ORDER TO REDUCE THE NEGATIVE IMPACTS OF DIABETES ON SUBSEQUENT GENERATIONS. 2021 5 6088 34 THE EFFECTS OF ASSISTED REPRODUCTION TECHNOLOGIES ON METABOLIC HEALTH AND DISEASEDAGGER. THE INCREASING PREVALENCE OF METABOLIC DISEASES PLACES A SUBSTANTIAL BURDEN ON HUMAN HEALTH THROUGHOUT THE WORLD. IT IS BELIEVED THAT PREDISPOSITION TO METABOLIC DISEASE STARTS EARLY IN LIFE, A PERIOD OF GREAT SUSCEPTIBILITY TO EPIGENETIC REPROGRAMMING DUE TO ENVIRONMENTAL INSULTS. ASSISTED REPRODUCTIVE TECHNOLOGIES (ART), I.E., TREATMENTS FOR INFERTILITY, MAY AFFECT EMBRYO DEVELOPMENT, RESULTING IN MULTIPLE ADVERSE HEALTH OUTCOMES IN POSTNATAL LIFE. THE MOST FREQUENTLY OBSERVED ALTERATION IN ART PREGNANCIES IS IMPAIRED PLACENTAL NUTRIENT TRANSFER. MOREOVER, CONSEQUENT INTRAUTERINE GROWTH RESTRICTION AND LOW BIRTH WEIGHT FOLLOWED BY CATCH-UP GROWTH CAN ALL PREDICT FUTURE OBESITY, INSULIN RESISTANCE, AND CHRONIC METABOLIC DISEASES. IN THIS REVIEW, WE HAVE FOCUSED ON EVIDENCE OF ADVERSE METABOLIC ALTERATIONS ASSOCIATED WITH ART, WHICH CAN CONTRIBUTE TO THE DEVELOPMENT OF CHRONIC ADULT-ONSET DISEASES, SUCH AS METABOLIC SYNDROME, TYPE 2 DIABETES, AND CARDIOVASCULAR DISEASE. DUE TO HIGH PHENOTYPIC PLASTICITY, ART PREGNANCIES CAN PRODUCE BOTH OFFSPRING WITH ADVERSE HEALTH OUTCOMES, AS WELL AS HEALTHY INDIVIDUALS. WE FURTHER DISCUSS THE SEX-SPECIFIC AND AGE-DEPENDENT METABOLIC ALTERATIONS REFLECTED IN ART OFFSPRING, AND HOW THE DEGREE OF INTERFERENCE OF A GIVEN ART PROCEDURE (FROM MILD TO MORE SEVERE MANIPULATION OF THE EGG) AFFECTS THE OCCURRENCE AND DEGREE OF OFFSPRING ALTERATIONS. OVER THE LAST FEW YEARS, STUDIES HAVE REPORTED SIGNS OF CARDIOMETABOLIC ALTERATIONS IN ART OFFSPRING THAT ARE DETECTABLE AT A YOUNG AGE BUT THAT DO NOT APPEAR TO CONSTITUTE A HIGH RISK OF DISEASE AND MORBIDITY PER SE. THESE ABNORMAL PHENOTYPES COULD BE EARLY INDICATORS OF THE DEVELOPMENT OF CHRONIC DISEASES, INCLUDING METABOLIC SYNDROME, IN ADULTHOOD. THE EARLY DETECTION OF METABOLIC ALTERATIONS COULD CONTRIBUTE TO PREVENTING THE ONSET OF DISEASE IN ADULTHOOD. SUCH EARLY INTERVENTIONS MAY COUNTERACT THE RISK FACTORS AND IMPROVE THE LONG-TERM HEALTH OF THE INDIVIDUAL. 2021 6 4468 30 MOLECULAR MECHANISMS UNDERLYING THE RELATIONSHIP BETWEEN OBESITY AND MALE INFERTILITY. IN RECENT DECADES, THE WORLDWIDE PREVALENCE OF OBESITY HAS RISEN DRAMATICALLY AND IS CURRENTLY ESTIMATED TO BE AROUND 20%. OBESITY IS LINKED TO AN INCREASED RISK OF COMORBIDITIES AND PREMATURE MORTALITY. SEVERAL STUDIES HAVE SHOWN THAT OBESITY NEGATIVELY IMPACTS MALE FERTILITY THROUGH VARIOUS MECHANISMS. THIS REVIEW AIMS TO INVESTIGATE THE MOLECULAR MECHANISMS THROUGH WHICH OBESITY IMPAIRS MALE REPRODUCTION, INCLUDING OBESITY-ASSOCIATED HYPOGONADISM AND ITS EFFECTS ON SPERMATOGENESIS, CHRONIC INFLAMMATION, AND OXIDATIVE STRESS. OBESITY NEGATIVELY IMPACTS BOTH CONVENTIONAL AND BIOFUNCTIONAL SPERM PARAMETERS, AND IT ALSO INDUCES EPIGENETIC CHANGES THAT CAN BE TRANSFERRED TO OFFSPRING. MOREOVER, OBESITY-RELATED DISEASES ARE LINKED TO A DYSREGULATION OF ADIPOCYTE FUNCTION AND MICRO-ENVIRONMENTAL INFLAMMATORY PROCESSES. THE DYSREGULATED ADIPOKINES SIGNIFICANTLY INFLUENCE INSULIN SIGNALING, AND THEY MAY ALSO HAVE A DETRIMENTAL EFFECT ON TESTICULAR FUNCTION. SIRTUINS CAN ALSO PLAY AN IMPORTANT ROLE IN INFLAMMATORY AND METABOLIC RESPONSES IN OBESE PATIENTS. UNDERSTANDING THE MOLECULAR MECHANISMS THAT ARE INVOLVED IN OBESITY-INDUCED MALE INFERTILITY COULD INCREASE OUR ABILITY TO IDENTIFY NOVEL TARGETS FOR THE PREVENTION AND TREATMENT OF OBESITY AND ITS RELATED CONSEQUENCES. 2021 7 4942 30 PATERNAL OBESITY: HOW BAD IS IT FOR SPERM QUALITY AND PROGENY HEALTH? THERE IS SUBSTANTIAL EVIDENCE THAT PATERNAL OBESITY IS ASSOCIATED NOT ONLY WITH AN INCREASED INCIDENCE OF INFERTILITY, BUT ALSO WITH AN INCREASED RISK OF METABOLIC DISTURBANCE IN ADULT OFFSPRING. APPARENTLY, SEVERAL MECHANISMS MAY CONTRIBUTE TO THE SPERM QUALITY ALTERATIONS ASSOCIATED WITH PATERNAL OBESITY, SUCH AS PHYSIOLOGICAL/HORMONAL ALTERATIONS, OXIDATIVE STRESS, AND EPIGENETIC ALTERATIONS. ALONG THESE LINES, MODIFICATIONS OF HORMONAL PROFILES NAMELY REDUCED ANDROGEN LEVELS AND ELEVATED ESTROGEN LEVELS, WERE FOUND ASSOCIATED WITH LOWER SPERM CONCENTRATION AND SEMINAL VOLUME. ADDITIONALLY, OXIDATIVE STRESS IN TESTIS MAY INDUCE AN INCREASE OF THE PERCENTAGE OF SPERM WITH DNA FRAGMENTATION. THE LATTER, RELATE TO OTHER PECULIARITIES SUCH AS ALTERATION OF THE EMBRYONIC DEVELOPMENT, INCREASED RISK OF MISCARRIAGE, AND DEVELOPMENT OF CHRONIC MORBIDITY IN THE OFFSPRING, INCLUDING CHILDHOOD CANCERS. UNDOUBTEDLY, EPIGENETIC ALTERATIONS (IE, DNA METHYLATION, CHROMATIN MODIFICATIONS, AND SMALL RNA DEREGULATION) OF SPERM RELATED TO PATERNAL OBESITY AND THEIR CONSEQUENCES ON THE PROGENY ARE POORLY UNDERSTOOD DETERMINANTS OF PATERNAL OBESITY-INDUCED TRANSMISSION. IN THIS REVIEW, WE SUMMARIZE AND DISCUSS THE DATA AVAILABLE IN THE LITERATURE REGARDING THE BIOLOGICAL, PHYSIOLOGICAL, AND MOLECULAR CONSEQUENCES OF PATERNAL OBESITY ON MALE FERTILITY POTENTIAL AND ULTIMATELY PROGENY HEALTH. 2017 8 1376 24 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 9 2699 26 EXCESS BODY WEIGHT: NOVEL INSIGHTS INTO ITS ROLES IN OBESITY COMORBIDITIES. EXCESS BODY WEIGHT IS A GLOBAL HEALTH PROBLEM DUE TO SEDENTARY LIFESTYLE AND UNHEALTHY DIET, AFFECTING 2 BILLION POPULATION WORLDWIDE. OBESITY IS A MAJOR RISK FACTOR FOR METABOLIC DISEASES. NOTABLY, THE METABOLIC RISK OF OBESITY LARGELY DEPENDS ON BODY WEIGHT DISTRIBUTION, OF WHICH VISCERAL ADIPOSE TISSUES BUT NOT SUBCUTANEOUS FATS ARE CLOSELY ASSOCIATED WITH OBESITY COMORBIDITIES, INCLUDING TYPE 2 DIABETES, NON-ALCOHOLIC FATTY LIVER DISEASE, CARDIOVASCULAR DISEASE AND CERTAIN TYPES OF CANCER. LATEST MULTI-OMICS AND MECHANISTICAL STUDIES REPORTED THE CRUCIAL INVOLVEMENT OF GENETIC AND EPIGENETIC ALTERATIONS, ADIPOKINES DYSREGULATION, IMMUNITY CHANGES, IMBALANCE OF WHITE AND BROWN ADIPOSE TISSUES, AND GUT MICROBIAL DYSBIOSIS IN MEDIATING THE PATHOGENIC ASSOCIATION BETWEEN VISCERAL ADIPOSE TISSUES AND COMORBIDITIES. IN THIS REVIEW, WE EXPLORE THE EPIDEMIOLOGY OF EXCESS BODY WEIGHT AND THE UP-TO-DATE MECHANISM OF HOW EXCESS BODY WEIGHT AND OBESITY LEAD TO CHRONIC COMPLICATIONS. WE ALSO EXAMINE THE UTILIZATION OF VISCERAL FAT MEASUREMENT AS AN ACCURATE CLINICAL PARAMETER FOR RISK ASSESSMENT IN HEALTHY INDIVIDUALS AND CLINICAL OUTCOME PREDICTION IN OBESE SUBJECTS. IN ADDITION, CURRENT APPROACHES FOR THE PREVENTION AND TREATMENT OF EXCESS BODY WEIGHT AND ITS RELATED METABOLIC COMORBIDITIES ARE FURTHER DISCUSSED. 2023 10 6234 28 THE LONG-TERM EFFECTS OF PRENATAL DEVELOPMENT ON GROWTH AND METABOLISM. PEOPLE WHO WERE SMALL AT BIRTH AND HAD POOR INFANT GROWTH HAVE AN INCREASED RISK OF ADULT CARDIOVASCULAR DISEASE, OSTEOPOROSIS, AND TYPE 2 DIABETES, PARTICULARLY IF THEIR RESTRICTED EARLY GROWTH WAS FOLLOWED BY INCREASED CHILDHOOD WEIGHT GAIN. THESE RELATIONS EXTEND ACROSS THE NORMAL RANGE OF BIRTH SIZE IN A GRADED MANNER, SO REDUCED SIZE IS NOT A PREREQUISITE. IN ADDITION, LARGER BIRTH SIZE IS ASSOCIATED WITH RISKS OF OBESITY AND TYPE 2 DIABETES. THE ASSOCIATIONS APPEAR TO REFLECT DEVELOPMENTAL PLASTIC RESPONSES MADE BY THE FETUS AND INFANT BASED ON CUES ABOUT THE ENVIRONMENT, INFLUENCED BY MATERNAL CHARACTERISTICS INCLUDING DIET, BODY COMPOSITION, STRESS, AND EXERCISE LEVELS. THESE RESPONSES INVOLVE EPIGENETIC PROCESSES THAT MODIFY THE OFFSPRING'S PHENOTYPE. VULNERABILITY TO ILL HEALTH RESULTS IF THE ENVIRONMENT IN INFANCY, CHILDHOOD, AND LATER LIFE IS MISMATCHED TO THE PHENOTYPE INDUCED IN DEVELOPMENT, INFORMED BY THE DEVELOPMENTAL CUES. THIS MISMATCH MAY ARISE THROUGH UNBALANCED DIET OR BODY COMPOSITION OF THE MOTHER OR A CHANGE IN LIFESTYLE FACTORS BETWEEN GENERATIONS. THESE INSIGHTS OFFER NEW POSSIBILITIES FOR THE EARLY DIAGNOSIS AND PREVENTION OF CHRONIC DISEASE. 2011 11 3707 29 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 12 2801 29 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 13 3311 29 HIGHLIGHTING THE TRAJECTORY FROM INTRAUTERINE GROWTH RESTRICTION TO FUTURE OBESITY. DURING THE LAST DECADES SEVERAL LINES OF EVIDENCE REPORTED THE ASSOCIATION OF AN ADVERSE INTRAUTERINE ENVIRONMENT, LEADING TO INTRAUTERINE RESTRICTION, WITH FUTURE DISEASE, SUCH AS OBESITY AND METABOLIC SYNDROME, BOTH LEADING TO INCREASED CARDIOVASCULAR AND CANCER RISK. THE UNDERLYING EXPLANATION FOR THIS ASSOCIATION HAS FIRSTLY BEEN EXPRESSED BY THE BARKER'S HYPOTHESIS, THE "THRIFTY PHENOTYPE HYPOTHESIS". ACCORDING TO THIS HYPOTHESIS, A FETUS FACING AN ADVERSE INTRAUTERINE ENVIRONMENT ADAPTS TO THIS ENVIRONMENT THROUGH A REPROGRAMMING OF ITS ENDOCRINE-METABOLIC STATUS, DURING THE CRUCIAL WINDOW OF DEVELOPMENTAL PLASTICITY TO SAVE ENERGY FOR SURVIVAL, PROVIDING LESS ENERGY AND NUTRIENTS TO THE ORGANS THAT ARE NOT ESSENTIAL FOR SURVIVAL. THIS THEORY EVOLVED TO THE CONCEPT OF THE DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASE (DOHAD). THUS, IN THE SETTING OF AN ADVERSE, F. EX. PROTEIN RESTRICTED INTRAUTERINE ENVIRONMENT, WHILE THE ENERGY IS MAINLY DIRECTED TO THE BRAIN, THE PERIPHERAL ORGANS, F.EX. THE MUSCLES AND THE LIVER UNDERGO AN ADAPTATION THAT IS EXPRESSED THROUGH INSULIN RESISTANCE. THE ADAPTATION AT THE HEPATIC LEVEL PREDISPOSES TO FUTURE DYSLIPIDEMIA, THE MODIFICATIONS AT THE VASCULAR LEVEL TO ENDOTHELIAL DAMAGE AND FUTURE HYPERTENSION AND, OVERALL, THROUGH THE INSULIN RESISTANCE TO THE DEVELOPMENT OF METABOLIC SYNDROME. ALL THESE ADAPTATIONS ARE SUGGESTED TO TAKE PLACE THROUGH EPIGENETIC MODIFICATIONS OF THE EXPRESSION OF GENES WITHOUT CHANGE OF THEIR AMINO-ACID SEQUENCE. THE EPIGENETIC MODIFICATIONS LEADING TO FUTURE OBESITY AND CARDIOVASCULAR RISK ARE THOUGHT TO INDUCE APPETITE DYSREGULATION, PROMOTING FOOD INTAKE AND ADIPOGENESIS, FACILITATING OBESITY DEVELOPMENT. THE EPIGENETIC MODIFICATIONS MAY EVEN PERSIST INTO THE NEXT GENERATION EVEN THOUGH THE SUBSEQUENT GENERATION HAS NOT BEEN EXPOSED TO AN ADVERSE INTRAUTERINE ENVIRONMENT, A NOTION DEFINED AS THE "TRANSGENERATIONAL TRANSFER OF ENVIRONMENTAL INFORMATION". AS A CONSEQUENCE, IF THE INCREASED PUBLIC HEALTH BURDEN AND COSTS OF NON-COMMUNICABLE CHRONIC DISEASES SUCH AS OBESITY, HYPERTENSION, METABOLIC SYNDROME AND TYPE 2 DIABETES HAVE TO BE MINIMIZED, SPECIAL ATTENTION SHOULD BE LAID TO THE HEALTHY LIFESTYLE HABITS OF WOMEN OF REPRODUCTIVE AGE, INCLUDING HEALTHY DIET AND PHYSICAL ACTIVITY TO BE ESTABLISHED LONG BEFORE ANY PREGNANCY TAKES PLACE IN ORDER TO PROVIDE THE BEST CONDITIONS FOR BOTH SOMATIC AND MENTAL HEALTH OF FUTURE GENERATIONS. 2022 14 4087 31 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 15 4782 26 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 16 1638 26 DOES EARLY WEANING SHAPE FUTURE ENDOCRINE AND METABOLIC DISORDERS? LESSONS FROM ANIMAL MODELS. OBESITY AND ITS COMPLICATIONS OCCUR AT ALARMING RATES WORLDWIDE. EPIDEMIOLOGICAL DATA HAVE ASSOCIATED PERINATAL CONDITIONS, SUCH AS MALNUTRITION, WITH THE DEVELOPMENT OF SOME DISORDERS, SUCH AS OBESITY, DYSLIPIDEMIA, DIABETES, AND CARDIOVASCULAR DISEASES, IN CHILDHOOD AND ADULTHOOD. EXCLUSIVE BREASTFEEDING HAS BEEN ASSOCIATED WITH PROTECTION AGAINST LONG-TERM CHRONIC DISEASES. HOWEVER, IN HUMANS, THE INTERRUPTION OF BREASTFEEDING BEFORE THE RECOMMENDED PERIOD OF 6 MONTHS IS A COMMON PRACTICE AND CAN INCREASE THE RISK OF SEVERAL METABOLIC DISTURBANCES. NUTRITIONAL AND ENVIRONMENTAL CHANGES WITHIN A CRITICAL WINDOW OF DEVELOPMENT, SUCH AS PREGNANCY AND BREASTFEEDING, CAN INDUCE PERMANENT CHANGES IN METABOLISM THROUGH EPIGENETIC MECHANISMS, LEADING TO DISEASES LATER IN LIFE VIA A PHENOMENON KNOWN AS PROGRAMMING OR DEVELOPMENTAL PLASTICITY. HOWEVER, LITTLE IS KNOWN REGARDING THE UNDERLYING MECHANISMS BY WHICH PRECOCIOUS WEANING CAN RESULT IN ADIPOSE TISSUE DYSFUNCTION AND ENDOCRINE PROFILE ALTERATIONS. HERE, THE AUTHORS GIVE A COMPREHENSIVE REPORT OF THE DIFFERENT ANIMAL MODELS OF EARLY WEANING AND PROGRAMMING THAT CAN RESULT IN THE DEVELOPMENT OF METABOLIC SYNDROME. IN RATS, FOR EXAMPLE, PHARMACOLOGICAL AND NONPHARMACOLOGICAL EARLY WEANING MODELS ARE ASSOCIATED WITH THE DEVELOPMENT OF OVERWEIGHT AND VISCERAL FAT ACCUMULATION, LEPTIN AND INSULIN RESISTANCE, AND NEUROENDOCRINE AND HEPATIC CHANGES IN ADULT PROGENY. SEX-RELATED DIFFERENCES SEEM TO INFLUENCE THIS PHENOTYPE. THEREFORE, PRECOCIOUS WEANING SEEMS TO BE OBESOGENIC FOR OFFSPRING. A BETTER UNDERSTANDING OF THIS CONDITION SEEMS ESSENTIAL TO REDUCING THE RISK FOR DISEASES. ADDITIONALLY, THIS KNOWLEDGE CAN GENERATE NEW INSIGHTS INTO THERAPEUTIC STRATEGIES FOR OBESITY MANAGEMENT, IMPROVING HEALTH OUTCOMES. 2020 17 1801 28 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 18 6873 23 [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 19 4802 28 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 20 3572 27 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