1 2605 85 EPIGENETICS-A POTENTIAL MEDIATOR BETWEEN AIR POLLUTION AND PRETERM BIRTH. PRETERM BIRTH IS A MAJOR CAUSE OF INFANT MORBIDITY AND MORTALITY AND A POTENTIAL RISK FACTOR FOR ADULT CHRONIC DISEASE. WITH OVER 15 MILLION INFANTS BORN PRETERM WORLDWIDE EACH YEAR, PRETERM BIRTH POSES A GLOBAL HEALTH CONCERN. THERE IS A POSSIBLE ASSOCIATION BETWEEN AIR POLLUTION AND PRETERM BIRTH, THOUGH STUDIES HAVE BEEN INCONSISTENT, LIKELY DUE TO VARIATION IN STUDY DESIGN. HOW AIR POLLUTION INDUCES HEALTH EFFECTS IS UNCERTAIN; HOWEVER, STUDIES HAVE REPEATEDLY DEMONSTRATED THE EFFECTS OF AIR POLLUTION ON EPIGENETIC MODIFICATIONS. MORE RECENT EVIDENCE SUGGESTS THAT EPIGENETICS MAY, IN TURN, BE LINKED TO PRETERM BIRTH. DISCOVERY OF ENVIRONMENTALLY MODIFIABLE EPIGENETIC PROCESSES CONNECTED TO PRETERM BIRTH MAY HELP TO IDENTIFY WOMEN AT RISK OF PRETERM BIRTH, AND ULTIMATELY LEAD TO DEVELOPMENT OF NEW PRETERM BIRTH PREVENTION MEASURES. 2016 2 6030 27 THE BURGEONING CARDIOVASCULAR DISEASE EPIDEMIC IN INDIANS - PERSPECTIVES ON CONTEXTUAL FACTORS AND POTENTIAL SOLUTIONS. CARDIOVASCULAR DISEASES (CVD) ARE THE LEADING CAUSE OF DEATH AND DISABILITY IN INDIA. THE CVD EPIDEMIC IN INDIANS IS CHARACTERIZED BY A HIGHER RELATIVE RISK BURDEN, AN EARLIER AGE OF ONSET, HIGHER CASE FATALITY AND HIGHER PREMATURE DEATHS. FOR DECADES, RESEARCHERS HAVE BEEN TRYING TO UNDERSTAND THE REASON FOR THIS INCREASED BURDEN AND PROPENSITY OF CVD AMONG INDIANS. IT CAN PARTLY BE EXPLAINED BY POPULATION-LEVEL CHANGES AND THE REMAINING BY INCREASED INHERENT BIOLOGICAL RISK. WHILE INCREASED BIOLOGICAL RISK CAN BE ATTRIBUTED TO PHENOTYPIC CHANGES CAUSED BY EARLY LIFE INFLUENCES, SIX MAJOR TRANSITIONS CAN BE CONSIDERED LARGELY RESPONSIBLE FOR THE POPULATION-LEVEL CHANGES IN INDIA-EPIDEMIOLOGICAL, DEMOGRAPHIC, NUTRITIONAL, ENVIRONMENTAL, SOCIAL-CULTURAL AND ECONOMIC. ALTHOUGH CONVENTIONAL RISK FACTORS EXPLAIN SUBSTANTIAL POPULATION ATTRIBUTABLE RISK, THE THRESHOLDS AT WHICH THESE RISK FACTORS OPERATE ARE DIFFERENT AMONG INDIANS COMPARED WITH OTHER POPULATIONS. THEREFORE, ALTERNATE EXPLANATIONS FOR THESE ECOLOGICAL DIFFERENCES HAVE BEEN SOUGHT AND MULTIPLE HYPOTHESES HAVE BEEN PROPOSED OVER THE YEARS. PRENATAL FACTORS THAT INCLUDE MATERNAL AND PATERNAL INFLUENCES ON THE OFFSPRING, AND POSTNATAL FACTORS, RANGING FROM BIRTH THROUGH CHILDHOOD, ADOLESCENCE AND YOUNG ADULTHOOD, AS WELL AS INTER-GENERATIONAL INFLUENCES HAVE BEEN EXPLORED USING THE LIFE COURSE APPROACH TO CHRONIC DISEASE. IN ADDITION TO THIS, RECENT RESEARCH HAS ILLUSTRATED THE IMPORTANCE OF THE ROLE OF INHERENT BIOLOGICAL DIFFERENCES IN LIPID METABOLISM, GLUCOSE METABOLISM, INFLAMMATORY STATES, GENETIC PREDISPOSITIONS AND EPIGENETIC INFLUENCES FOR THE INCREASED RISK. A MULTIFACETED AND HOLISTIC APPROACH TO CVD PREVENTION THAT TAKES INTO CONSIDERATION POPULATION-LEVEL AS WELL AS BIOLOGICAL RISK FACTORS WOULD BE NEEDED TO CONTROL THE BURGEONING CVD EPIDEMIC AMONG INDIANS. 2023 3 6173 25 THE HEALTH OUTCOMES OF HUMAN OFFSPRING CONCEIVED BY ASSISTED REPRODUCTIVE TECHNOLOGIES (ART). CONCERNS HAVE BEEN RAISED ABOUT THE HEALTH AND DEVELOPMENT OF CHILDREN CONCEIVED BY ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) SINCE 1978. CONTROVERSIALLY, ART HAS BEEN LINKED WITH ADVERSE OBSTETRIC AND PERINATAL OUTCOMES, AN INCREASED RISK OF BIRTH DEFECTS, CANCERS, AND GROWTH AND DEVELOPMENT DISORDERS. EMERGING EVIDENCE SUGGESTS THAT ART TREATMENT MAY ALSO PREDISPOSE INDIVIDUALS TO AN INCREASED RISK OF CHRONIC AGEING RELATED DISEASES SUCH AS OBESITY, TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE. THIS REVIEW WILL SUMMARIZE THE AVAILABLE EVIDENCE ON THE SHORT-TERM AND LONG-TERM HEALTH OUTCOMES OF ART SINGLETONS, AS MULTIPLE PREGNANCIES AFTER MULTIPLE EMBRYOS TRANSFER, ARE ASSOCIATED WITH LOW BIRTH WEIGHT AND PRETERM DELIVERY, WHICH CAN SEPARATELY INCREASE RISK OF ADVERSE POSTNATAL OUTCOMES, AND IMPACT LONG-TERM HEALTH. WE WILL ALSO EXAMINE THE POTENTIAL FACTORS THAT MAY CONTRIBUTE TO THESE HEALTH RISKS, AND DISCUSS UNDERLYING MECHANISMS, INCLUDING EPIGENETIC CHANGES THAT MAY OCCUR DURING THE PREIMPLANTATION PERIOD AND REPROGRAM DEVELOPMENT IN UTERO, AND ADULT HEALTH, LATER IN LIFE. LASTLY, THIS REVIEW WILL CONSIDER THE FUTURE DIRECTIONS WITH THE VIEW TO OPTIMIZE THE LONG-TERM HEALTH OF ART CHILDREN. 2017 4 1370 28 DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE THEORY IN CARDIOLOGY. NUMEROUS EPIDEMIOLOGICAL AND ANIMAL STUDIES DISCLOSED THAT BIRTH WEIGHT IS INVERSELY ASSOCIATED WITH THE INCIDENCE OF THE LIFESTYLE-RELATED DISORDERS IN ADULT LIFE, SUCH AS CARDIOVASCULAR DISEASE, DIABETES, AND /OR CHRONIC KIDNEY DISEASE. LOWER BIRTH WEIGHT OCCURS IN NUMEROUS UNDESIRED INTRAUTERINE ENVIRONMENTS INCLUDING MALNUTRITION, SMOKING, ALCOHOL CONSUMPTION, OR STRESS. THE DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASE (DOHAD) THEORY IS BASED ON THE CONCEPT THAT THE ORIGINS OF LIFESTYLE-RELATED DISEASE IS FORMED AT THE TIME OF FERTILIZATION, EMBRYONIC, FETAL, AND NEONATAL STAGES BY THE INTERRELATION BETWEEN GENES AND THE ENVIRONMENTS (NUTRITION, STRESS, OR ENVIRONMENTAL CHEMICALS). ADULT DISEASE DEVELOPS AFTER DELIVERY FACING TO ABNORMAL ENVIRONMENTS SUCH AS OVER-NUTRITION, MUCH STRESS, OR LACK OF EXERCISE. DISEASE DEVELOPS THROUGH THESE TWO INSULTS. THIS CONCEPT WAS FIRST PROPOSED AS THE "BARKER HYPOTHESIS." DAVID BARKER HAD DISCOVERED THE RELATION BETWEEN THE LOWER BIRTH WEIGHT AND THE HIGHER PREVALENCE OF ISCHEMIC HEART DISEASE MORTALITY. PREVIOUS EPIDEMIOLOGIC STUDIES HAVE FOUND THE PEOPLE EXPOSED TO FAMINE DURING EARLY LIFE HAD HIGHER RISKS OF CARDIOVASCULAR DISEASES IN ADULTHOOD. YET, THE EXACT MECHANISMS THAT PERMANENTLY CHANGE THE STRUCTURE, PHYSIOLOGY, AND ENDOCRINE STATUS OF AN INDIVIDUAL ACROSS THEIR LIFESPAN FOLLOWING ALTERED GROWTH DURING FETAL LIFE ARE NOT ENTIRELY CLEAR. EPIDEMIOLOGICAL STUDIES INCLUDING PROSPECTIVE COHORT AND OBSERVATIONAL ANALYSIS OF THE PEOPLE EXPOSED TO MALNUTRITION DURING FETAL OR INFANCY HAVE DISCLOSED THE STRONG RELATION BETWEEN THE LOWER BIRTH WEIGHT AND THE HIGHER CARDIOVASCULAR RISKS IN ADULTS. RECENT PROGRESS OF EPIGENETIC STUDIES UNVEILED STRONG GENETIC ASSOCIATION. HORMONAL REGULATION AND EPIGENETIC MODIFICATIONS HAVE AN IMPORTANT ROLE FOR PROPER ORGAN DEVELOPMENT AND PHYSIOLOGICAL FUNCTIONS. THE MOLECULAR MECHANISM OF PREDISPOSITION IS SUPPOSED TO BE THE EPIGENETICS MODIFICATIONS. THEIR DYSREGULATION IS RELATED TO THE ACQUISITION OF THE DISEASE-SUSCEPTIBLE TRAIT. IN THIS REVIEW, WE OVERVIEW THE CONCEPT OF DOHAD AND INTRODUCE RELATED CLINICAL AND BASIC RESEARCH. 2020 5 6822 30 [GENDER MEDICINE. SEX- AND GENDER-SPECIFIC ASPECTS OF CLINICAL MEDICINE]. GENDER MEDICINE STUDIES SEX- AND GENDER-BASED DIFFERENCES IN THE DEVELOPMENT AND PREVENTION OF DISEASES, THE AWARENESS AND PRESENTATION OF SYMPTOMS, AND THE EFFECTIVENESS OF THERAPY. GENDER MEDICINE IS PART OF PERSONALIZED MEDICINE, CONSIDERING DIFFERENCES IN BIOLOGICAL AND PSYCHOSOCIAL FACTORS INDIVIDUALLY. THERE ARE DIFFERENCES IN GENES, CHROMOSOMES, HORMONES, AND METABOLISM AS WELL AS DIFFERENCES IN CULTURE, ENVIRONMENT, AND SOCIETY. LIFELONG INTERACTIONS BETWEEN PHYSICAL AND PSYCHOSOCIAL FACTORS WILL INFLUENCE THE HEALTH AND ILL-HEALTH OF MEN AND WOMEN IN DIFFERENT WAYS. EPIGENETIC MODIFICATIONS PROVIDE EVIDENCE OF THE IMPACT OF ENVIRONMENT AND LIFESTYLE DURING VULNERABLE PHASES ON BIOLOGICAL PROCESSES, EFFECTING FUTURE GENERATIONS. MATERNAL LIFESTYLE AND ENVIRONMENTAL FACTORS DURING PREGNANCY CAN IMPACT THE HEALTH OF OFFSPRING IN LATER LIFE ALREADY IN UTERO IN A SEX-SPECIFIC WAY. PAIN, STRESS, AND COPING STYLES DIFFER BETWEEN MEN AND WOMEN. WOMEN EXPERIENCE MORE DRAMATIC PHYSICAL CHANGES DURING THEIR LIFETIME, WHICH ARE ASSOCIATED WITH SPECIFIC BURDENS AND PSYCHOSOCIAL ALTERATIONS. WOMEN WITH MULTIPLE ROLES AND RESPONSIBILITIES SUFFERING FROM STRESS DEVELOP DEPRESSION MORE FREQUENTLY. HOWEVER, MEN ARE OFTEN NOT DIAGNOSED AND TREATED APPROPRIATELY IN CASES OF DEPRESSION OR OSTEOPOROSIS, DISEASES THAT ARE TYPICALLY CONSIDERED "FEMALE." THERE ARE PROMINENT DIFFERENCES BETWEEN MEN AND WOMEN IN MEDICINE REGARDING THE IMMUNE SYSTEM, INFLAMMATION, AND NONCOMMUNICABLE DISEASES SUCH AS OBESITY, TYPE 2 DIABETES, HYPERTENSION, AND CARDIOVASCULAR DISEASE. WOMEN EXPERIENCE MORE OFTEN AUTOIMMUNE DISEASES AND SUFFER MORE FREQUENTLY FROM (CHRONIC) PAIN, NEURODEGENERATIVE CHANGES, AND FUNCTIONAL DISABILITIES. MEN HAVE SHORTER LIFE EXPECTANCY BUT RELATIVELY MORE HEALTHY YEARS OF LIFE, WHICH IS IN GREATER PART ASCRIBED TO PSYCHOSOCIAL DETERMINANTS. STATE-OF-THE-ART CLINICAL MEDICINE COMPRISES INDIVIDUAL RISK FACTORS BASED ON SEX- AND GENDER-SENSITIVE HEALTH PROGRAMS IN ORDER TO IMPROVE THE HEALTH-RELATED QUALITY OF LIFE FOR MEN AND WOMEN. 2014 6 1385 33 DIABETES IN CHILDHOOD CANCER SURVIVORS: EMERGING CONCEPTS IN PATHOPHYSIOLOGY AND FUTURE DIRECTIONS. WITH ADVANCEMENTS IN CANCER TREATMENT AND SUPPORTIVE CARE, THERE IS A GROWING POPULATION OF CHILDHOOD CANCER SURVIVORS WHO EXPERIENCE A SUBSTANTIAL BURDEN OF COMORBIDITIES RELATED TO HAVING RECEIVED CANCER TREATMENT AT A YOUNG AGE. DESPITE AN OVERALL REDUCTION IN THE INCIDENCE OF MOST CHRONIC HEALTH CONDITIONS IN CHILDHOOD CANCER SURVIVORS OVER THE PAST SEVERAL DECADES, THE CUMULATIVE INCIDENCE OF CERTAIN LATE EFFECTS, IN PARTICULAR DIABETES MELLITUS (DM), HAS INCREASED. THE IMPLICATIONS ARE SIGNIFICANT, BECAUSE DM IS A KEY RISK FACTOR FOR CARDIOVASCULAR DISEASE, A LEADING CAUSE OF PREMATURE DEATH IN CHILDHOOD CANCER SURVIVORS. THE UNDERLYING PATHOPHYSIOLOGY OF DM IN CANCER SURVIVORS IS MULTIFACTORIAL. DM DEVELOPS AT YOUNGER AGES IN SURVIVORS COMPARED TO CONTROLS, WHICH MAY REFLECT AN "ACCELERATED AGING" PHENOTYPE IN THESE INDIVIDUALS. THE TREATMENT-RELATED EXPOSURES (I.E., CHEMOTHERAPY, RADIATION) THAT INCREASE RISK FOR DM IN CHILDHOOD CANCER SURVIVORS MAY BE MORE THAN ADDITIVE WITH ESTABLISHED DM RISK FACTORS (E.G., OLDER AGE, OBESITY, RACE, AND ETHNICITY). EMERGING RESEARCH ALSO POINTS TO PARALLELS IN CELLULAR PROCESSES IMPLICATED IN AGING- AND CANCER TREATMENT-RELATED DM. STILL, THERE REMAINS MARKED INTER-INDIVIDUAL VARIABILITY REGARDING RISK OF DM THAT IS NOT EXPLAINED BY DEMOGRAPHIC AND THERAPEUTIC RISK FACTORS ALONE. RECENT STUDIES HAVE HIGHLIGHTED THE ROLE OF GERMLINE GENETIC RISK FACTORS AND EPIGENETIC MODIFICATIONS THAT ARE ASSOCIATED WITH RISK OF DM IN BOTH THE GENERAL AND ONCOLOGY POPULATIONS. THIS REVIEW SUMMARIZES OUR CURRENT UNDERSTANDING OF RECOGNIZED RISK FACTORS FOR DM IN CHILDHOOD CANCER SURVIVORS TO HELP INFORM TARGETED APPROACHES FOR DISEASE SCREENING, PREVENTION, AND TREATMENT. FURTHERMORE, IT HIGHLIGHTS THE EXISTING SCIENTIFIC GAPS IN UNDERSTANDING THE RELATIVE CONTRIBUTIONS OF INDIVIDUAL THERAPEUTIC EXPOSURES AND THE MECHANISMS BY WHICH THEY EXERT THEIR EFFECTS THAT UNIQUELY PREDISPOSE THIS POPULATION TO DM FOLLOWING CANCER TREATMENT. 2023 7 6873 30 [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 8 4065 28 MATERNAL AND GESTATIONAL INFLUENCES ON CHILDHOOD BLOOD PRESSURE. EXPOSURES THAT CONTRIBUTE TO A SUB-OPTIMAL INTRAUTERINE ENVIRONMENT CAN HAVE AN EFFECT ON THE DEVELOPING FETUS. IMPAIRED FETAL GROWTH THAT RESULTS IN LOW BIRTH WEIGHT IS AN ESTABLISHED RISK FACTOR FOR CARDIO-METABOLIC DISORDERS LATER IN LIFE. RECENT EPIDEMIOLOGIC AND PROSPECTIVE COHORT STUDIES THAT INCLUDE THE MATERNAL AND GESTATIONAL PERIOD HAVE IDENTIFIED MATERNAL AND GESTATIONAL CONDITIONS THAT CONFER INCREASED RISK FOR SUBSEQUENT CARDIO-METABOLIC DISORDERS IN THE ABSENCE OF LOW BIRTH WEIGHT. MATERNAL PRE-CONCEPTION HEALTH STATUS, INCLUDING CHRONIC OBESITY AND TYPE 2 DIABETES, INCREASE RISK FOR CHILDHOOD OBESITY AND OBESITY-RELATED HIGHER BLOOD PRESSURE (BP) IN CHILD OFFSPRING. MATERNAL GESTATIONAL EXPOSURES, INCLUDING GESTATIONAL DIABETES, GESTATIONAL HYPERTENSION, AND PREECLAMPSIA, ARE ASSOCIATED WITH HIGHER BP IN OFFSPRING. OTHER MATERNAL EXPOSURES SUCH AS CIGARETTE SMOKE AND AIR POLLUTION ALSO INCREASE RISK FOR HIGHER BP IN CHILD OFFSPRING. RECENT, BUT LIMITED, DATA INDICATE THAT ASSISTED REPRODUCTIVE TECHNOLOGIES CAN BE ASSOCIATED WITH HYPERTENSION IN CHILDHOOD, DESPITE OTHERWISE NORMAL GESTATION AND HEALTHY NEWBORN. GESTATIONAL EXPOSURES ASSOCIATED WITH HIGHER BP IN CHILDHOOD CAN BE RELATED TO FAMILIAL LIFESTYLE FACTORS, GENETICS, OR EPIGENETIC MODIFICATION OF FETAL DEOXYRIBONUCLEIC ACID (DNA). THESE FACTORS, OR COMBINATION OF FACTORS, AS WELL AS OTHER ADVERSE INTRAUTERINE CONDITIONS, COULD INDUCE FETAL PROGRAMING LEADING TO HEALTH CONSEQUENCES IN LATER LIFE. CURRENT AND DEVELOPING RESEARCH WILL PROVIDE ADDITIONAL INSIGHTS ON GESTATIONAL EXPOSURES AND FETAL ADJUSTMENTS THAT INCREASE RISK FOR HIGHER BP LEVELS IN CHILDHOOD. 2020 9 2805 30 FETAL MALNUTRITION AND LONG-TERM OUTCOMES. EPIDEMIOLOGICAL STUDIES HAVE SHOWN THAT LOWER BIRTHWEIGHT IS ASSOCIATED WITH A WIDE RANGE OF ADVERSE OUTCOMES IN LATER LIFE, INCLUDING POORER 'HUMAN CAPITAL' (SHORTER STATURE, LOWER COGNITIVE PERFORMANCE), INCREASED RISK FACTORS FOR LATER DISEASE (HIGHER BLOOD PRESSURE AND REDUCED GLUCOSE TOLERANCE, AND LUNG, KIDNEY AND IMMUNE FUNCTION), CLINICAL DISEASE (DIABETES, CORONARY HEART DISEASE, CHRONIC LUNG AND KIDNEY DISEASE), AND INCREASED ALL-CAUSE AND CARDIOVASCULAR MORTALITY. HIGHER BIRTHWEIGHT IS ASSOCIATED WITH AN INCREASED RISK OF CANCER AND (IF CAUSED BY GESTATIONAL DIABETES) OBESITY AND DIABETES. THE 'DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE' HYPOTHESIS PROPOSES THAT FETAL NUTRITION HAS PERMANENT EFFECTS ON GROWTH, STRUCTURE AND METABOLISM ('PROGRAMMING'). THIS IS SUPPORTED BY STUDIES IN ANIMALS SHOWING THAT MATERNAL UNDER- AND OVERNUTRITION DURING PREGNANCY CAN PRODUCE SIMILAR ABNORMALITIES IN THE ADULT OFFSPRING. COMMON CHRONIC DISEASES COULD POTENTIALLY BE PREVENTED BY ACHIEVING OPTIMAL FETAL NUTRITION, AND THIS COULD HAVE ADDITIONAL BENEFITS FOR SURVIVAL AND HUMAN CAPITAL. RECENT FOLLOW-UP OF CHILDREN BORN AFTER RANDOMIZED NUTRITIONAL INTERVENTIONS IN PREGNANCY PROVIDES WEAK EVIDENCE OF BENEFICIAL EFFECTS ON GROWTH, VASCULAR FUNCTION, LIPID CONCENTRATIONS, GLUCOSE TOLERANCE AND INSULIN RESISTANCE. ANIMAL STUDIES INDICATE THAT EPIGENETIC PHENOMENA MAY BE AN IMPORTANT MECHANISM UNDERLYING PROGRAMMING, AND THAT NUTRITIONAL INTERVENTIONS MAY NEED TO START PRECONCEPTIONALLY. 2013 10 6088 33 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 11 4080 15 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 12 5216 33 PRETERM BIRTH: LONG TERM CARDIOVASCULAR AND RENAL CONSEQUENCES. BACKGROUND: CARDIOVASCULAR AND CHRONIC KIDNEY DISEASES ARE A PART OF NONCOMMUNICABLE CHRONIC DISEASES, THE LEADING CAUSES OF PREMATURE DEATH WORLDWIDE. THEY ARE RECOGNIZED AS HAVING EARLY ORIGINS THROUGH ALTERED DEVELOPMENTAL PROGRAMMING, DUE TO ADVERSE ENVIRONMENTAL CONDITIONS DURING DEVELOPMENT. PRETERM BIRTH IS SUCH AN ADVERSE FACTOR. RATES OF PRETERM BIRTH INCREASED IN THE LAST DECADES, HOWEVER, WITH THE IMPROVEMENT IN PERINATAL AND NEONATAL CARE, A GROWING NUMBER OF PRETERM BORN SUBJECTS HAS NOW ENTERED ADULTHOOD. CLINICAL AND EXPERIMENTAL EVIDENCE SUGGESTS THAT PRETERM BIRTH IS ASSOCIATED WITH IMPAIRED OR ARRESTED STRUCTURAL OR FUNCTIONAL DEVELOPMENT OF KEY ORGANS/SYSTEMS MAKING PRETERM INFANTS VULNERABLE TO CARDIOVASCULAR AND CHRONIC RENAL DISEASES AT ADULTHOOD. THIS REVIEW ANALYZES THE EVIDENCE OF SUCH CARDIOVASCULAR AND RENAL CHANGES, THE ROLE OF PERINATAL AND NEONATAL FACTORS SUCH AS ANTENATAL STEROIDS AND POTENTIAL PATHOGENIC MECHANISMS, INCLUDING DEVELOPMENTAL PROGRAMMING AND EPIGENETIC ALTERATIONS. CONCLUSION: PRETERM BORN SUBJECTS ARE EXPOSED TO A SIGNIFICANTLY INCREASED RISK FOR ALTERED CARDIOVASCULAR AND RENAL FUNCTIONS AT YOUNG ADULTHOOD. ADEQUATE, SPECIFIC FOLLOW-UP MEASURES REMAIN TO BE DETERMINED. WHILE ANTENATAL STEROIDS HAVE CONSIDERABLY IMPROVED PRETERM BIRTH OUTCOMES, REPEATED THERAPY SHOULD BE CONSIDERED WITH CAUTION, AS ANTENATAL STEROIDS INDUCE LONG-TERM CARDIOVASCULAR AND METABOLIC ALTERATIONS IN ANIMALS' MODELS AND THEIR INVOLVEMENT IN THE ACCELERATED CELLULAR SENESCENCE OBSERVED IN HUMAN STUDIES CANNOT BE EXCLUDED. 2018 13 1388 20 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE: NON-INVASIVE ASSESSMENT OF CARDIOVASCULAR RISK. THE PREVALENCE AND BURDEN OF DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE ON GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT IS ALREADY HEAVY AND STILL RISING. DIABETES MELLITUS BY ITSELF IS LINKED TO ADVERSE CARDIOVASCULAR EVENTS, AND THE PRESENCE OF CONCOMITANT CHRONIC KIDNEY DISEASE FURTHER AMPLIFIES CARDIOVASCULAR RISK. THE CULMINATION OF TRADITIONAL (MALE GENDER, SMOKING, ADVANCED AGE, OBESITY, ARTERIAL HYPERTENSION AND DYSLIPIDEMIA) AND NON-TRADITIONAL RISK FACTORS (ANEMIA, INFLAMMATION, PROTEINURIA, VOLUME OVERLOAD, MINERAL METABOLISM ABNORMALITIES, OXIDATIVE STRESS, ETC.) CONTRIBUTES TO ADVANCED ATHEROSCLEROSIS AND INCREASED CARDIOVASCULAR RISK. TO DECREASE THE MORBIDITY AND MORTALITY OF THESE PATIENTS DUE TO CARDIOVASCULAR CAUSES, TIMELY AND EFFICIENT CARDIOVASCULAR RISK ASSESSMENT IS OF HUGE IMPORTANCE. CARDIOVASCULAR RISK ASSESSMENT CAN BE BASED ON LABORATORY PARAMETERS, IMAGING TECHNIQUES, ARTERIAL STIFFNESS PARAMETERS, ANKLE-BRACHIAL INDEX AND 24 H BLOOD PRESSURE MEASUREMENTS. NEWER METHODS INCLUDE EPIGENETIC MARKERS, SOLUBLE ADHESION MOLECULES, CYTOKINES AND MARKERS OF OXIDATIVE STRESS. IN THIS REVIEW, THE AUTHORS PRESENT SEVERAL NON-INVASIVE METHODS OF CARDIOVASCULAR RISK ASSESSMENT IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE. 2021 14 6867 25 [PARENTAL AGEING AND ASSISTED REPRODUCTION TECHNOLOGIES: ANALYSIS OF RISK OF CHRONIC DISEASES IN THE PROGENY]. CONCEPTION OF A CHILD AT ADVANCED PARENTAL AGE (> 35 YEARS) HAS BEEN STEADILY INCREASING IN RECENT DECADES, ESPECIALLY IN DEVELOPED COUNTRIES. SOCIO-ECONOMIC FACTORS, EFFECTIVE CONTRACEPTIVES, AND THE AVAILABILITY OF ASSISTED REPRODUCTION TECHNOLOGIES (ART) HAVE A DIRECT IMPACT ON POSTPONING THE DECISION TO HAVE A BABY. ART ENABLES REPRODUCTIVE SUCCESS FOR PEOPLE DIAGNOSED AS INFERTILE OR WITH REDUCED POSSIBILITIES OF BECOMING PREGNANT DUE TO CONCOMITANT PATHOLOGIES. EPIDEMIOLOGICAL STUDIES INDICATE THAT BOTH ADVANCED PARENTAL AGE AND ART ARE ASSOCIATED WITH PATHOLOGIES OF PREGNANCY, SUCH AS GESTATIONAL DIABETES, RISK OF PRE-ECLAMPSIA, MISCARRIAGE, PLACENTAL ABRUPTION, PRETERM LABOR, STILLBIRTH, NEURODEVELOPMENTAL DISORDERS AND CHRONIC DISEASE OF THE OFFSPRING. IN OUR WORK, WE WILL FOCUS ON THE AVAILABLE INFORMATION ON METABOLIC CHANGES THAT INCREASE THE RISK OF DEVELOPING CARDIOVASCULAR DISEASES IN THE OFFSPRING OF PARENTS AT AN ADVANCED AGE AND CONCEIVED THROUGH ART. FINALLY, WE WILL ADDRESS THE SOURCES OF THE OBSERVED DISTURBANCES AT THE GAMETE AND EMBRYO LEVEL, RELATED TO OXYGEN STRESS, EPIGENETIC MODIFICATIONS AND DNA DAMAGE, CONSIDERING POSSIBLE RESCUE ACTIONS. 2022 15 6234 30 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 16 625 28 BIOLOGICAL AGE AND ENVIRONMENTAL RISK FACTORS FOR DEMENTIA AND STROKE: MOLECULAR MECHANISMS. SINCE THE DEVELOPMENT OF ANTIBIOTICS AND VACCINATION, AS WELL AS MAJOR IMPROVEMENTS IN PUBLIC HYGIENE, THE MAIN RISK FACTORS FOR MORBIDITY AND MORTALITY ARE AGE AND CHRONIC EXPOSURE TO ENVIRONMENTAL FACTORS, BOTH OF WHICH CAN INTERACT WITH GENETIC PREDISPOSITIONS. AS THE AVERAGE AGE OF THE POPULATION INCREASES, THE PREVALENCE AND COSTS OF CHRONIC DISEASES, ESPECIALLY NEUROLOGICAL CONDITIONS, ARE RAPIDLY INCREASING. THE DELETERIOUS EFFECTS OF AGE AND ENVIRONMENTAL RISK FACTORS, DEVELOP CHRONICALLY OVER RELATIVELY LONG PERIODS OF TIME, IN CONTRAST TO THE RELATIVELY RAPID DELETERIOUS EFFECTS OF INFECTIOUS DISEASES OR ACCIDENTS. OF PARTICULAR INTEREST IS THE HYPOTHESIS THAT THE DELETERIOUS EFFECTS OF ENVIRONMENTAL FACTORS MAY BE MEDIATED BY ACCELERATION OF BIOLOGICAL AGE. THIS HYPOTHESIS IS SUPPORTED BY EVIDENCE THAT DIETARY RESTRICTION, WHICH UNIVERSALLY DELAYS AGE-RELATED DISEASES, ALSO AMELIORATES DELETERIOUS EFFECTS OF ENVIRONMENTAL FACTORS. CONVERSELY, BOTH AGE AND ENVIRONMENTAL RISK FACTORS ARE ASSOCIATED WITH THE ACCUMULATION OF SOMATIC MUTATIONS IN MITOTIC CELLS AND EPIGENETIC MODIFICATIONS THAT ARE A MEASURE OF "BIOLOGICAL AGE", A BETTER PREDICTOR OF AGE-RELATED MORBIDITY AND MORTALITY THAN CHRONOLOGICAL AGE. HERE WE REVIEW EVIDENCE THAT ENVIRONMENTAL RISK FACTORS SUCH AS SMOKING AND AIR POLLUTION MAY ALSO DRIVE NEUROLOGICAL CONDITIONS, INCLUDING ALZHEIMER'S DISEASE, BY THE ACCELERATION OF BIOLOGICAL AGE, MEDIATED BY CUMULATIVE AND PERSISTENT EPIGENETIC EFFECTS AS WELL AS SOMATIC MUTATIONS. ELUCIDATION OF SUCH MECHANISMS COULD PLAUSIBLY ALLOW THE DEVELOPMENT OF INTERVENTIONS WHICH DELAY DELETERIOUS EFFECTS OF BOTH AGING AND ENVIRONMENTAL RISK FACTORS. 2022 17 2801 24 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 18 3573 23 IMPACT OF MATERNAL UNDERNUTRITION ON DIABETES AND CARDIOVASCULAR DISEASE RISK IN ADULT OFFSPRING. EPIDEMIOLOGICAL, CLINICAL, AND EXPERIMENTAL OBSERVATIONS HAVE LED TO THE HYPOTHESIS THAT THE RISK OF DEVELOPING CHRONIC DISEASES IN ADULTHOOD IS INFLUENCED NOT ONLY BY GENETIC AND ADULT LIFESTYLE FACTORS, BUT ALSO BY ENVIRONMENTAL FACTORS DURING EARLY LIFE. LOW BIRTH WEIGHT, A MARKER OF INTRAUTERINE STRESS, HAS BEEN LINKED TO PREDISPOSITION TO CARDIOVASCULAR DISEASE (CVD) AND DIABETES. THE COMPELLING ANIMAL EVIDENCE AND SIGNIFICANT HUMAN DATA TO SUPPORT THIS CONCLUSION ARE REVIEWED. SPECIFICALLY, THE REVIEW DISCUSSES THE ROLE OF MATERNAL NUTRITION BEFORE AND DURING PREGNANCY, PLACENTAL INSUFFICIENCIES AND EPIGENETIC CHANGES IN THE INCREASED PREDISPOSITION TO DIABETES AND CVD IN ADULT LIFE. THE IMPACT OF LOW BIRTH WEIGHT AND CATCH-UP GROWTH AS THEY PERTAIN TO RISK OF DISEASE IN ADULT LIFE IS ALSO DISCUSSED. IN ADDITION, ADULT DISEASE RISK IN THE OVERNOURISHED FETUS IS ALSO MENTIONED. REFERENCE IS MADE TO SOME OF THE MECHANISMS OF THE INDUCTION OF DIABETES AND CVD PHENOTYPE. IT IS PROPOSED THAT FETAL NUTRITION, GROWTH AND DEVELOPMENT THROUGH EFFICIENT MATERNAL NUTRITION BEFORE AND DURING PREGNANCY COULD CONSTITUTE THE BASIS FOR NUTRITIONAL STRATEGIES FOR THE PRIMARY PREVENTION OF DIABETES AND CVD. 2009 19 6109 27 THE EPIGENETIC AGING, OBESITY, AND LIFESTYLE. THE PREVALENCE OF OBESITY HAS DRAMATICALLY INCREASED WORLDWIDE OVER THE PAST DECADES. AGING-RELATED CHRONIC CONDITIONS, SUCH AS TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE, ARE MORE PREVALENT IN INDIVIDUALS WITH OBESITY, THUS REDUCING THEIR LIFESPAN. EPIGENETIC CLOCKS, THE NEW METRICS OF BIOLOGICAL AGE BASED ON DNA METHYLATION PATTERNS, COULD BE CONSIDERED A REFLECTION OF THE STATE OF ONE'S HEALTH. SEVERAL ENVIRONMENTAL EXPOSURES AND LIFESTYLE FACTORS CAN INDUCE EPIGENETIC AGING ACCELERATIONS, INCLUDING OBESITY, THUS LEADING TO AN INCREASED RISK OF AGE-RELATED DISEASES. THE INSIGHT INTO THE COMPLEX LINK BETWEEN OBESITY AND AGING MIGHT HAVE SIGNIFICANT IMPLICATIONS FOR THE PROMOTION OF HEALTH AND THE MITIGATION OF FUTURE DISEASE RISK. THE PRESENT NARRATIVE REVIEW TAKES INTO ACCOUNT THE INTERACTION BETWEEN EPIGENETIC AGING AND OBESITY, SUGGESTING THAT EPIGENOME MAY BE AN INTRIGUING TARGET FOR AGE-RELATED PHYSIOLOGICAL CHANGES AND THAT ITS MODIFICATION COULD INFLUENCE AGING AND PROLONG A HEALTHY LIFESPAN. THEREFORE, WE HAVE FOCUSED ON DNA METHYLATION AGE AS A CLINICAL BIOMARKER, AS WELL AS ON THE POTENTIAL REVERSAL OF EPIGENETIC AGE USING A PERSONALIZED DIET- AND LIFESTYLE-BASED INTERVENTION. 2022 20 6861 29 [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