1 1417 151 DIETARY TRENDS AND THE DECLINE IN MALE REPRODUCTIVE HEALTH. OVER THE TWENTIETH CENTURY, MALE REPRODUCTIVE HEALTH HAS SUFFERED A SUBSTANTIAL DECLINE, AS EVIDENCED BY DECREASES IN SPERM COUNTS AND TESTOSTERONE LEVELS AND INCREASES IN REPRODUCTIVE PATHOLOGIES. AT THE SAME TIME, THE PREVALENCE OF CHRONIC DISEASES SUCH AS OBESITY, DIABETES, AND METABOLIC SYNDROME HAS RISEN DRAMATICALLY. METABOLIC AND REPRODUCTIVE HEALTH ARE HIGHLY INTERCONNECTED, SUGGESTING THAT THEIR RESPECTIVE TRENDS ARE INTERTWINED AND, GIVEN THE TIMEFRAME OF SUCH TRENDS, ENVIRONMENTAL AND NOT GENETIC FACTORS ARE MOST LIKELY TO BE THE PRIMARY CAUSES. INDUSTRIALIZATION, WHICH BEGAN IN EUROPE IN THE MID-EIGHTEENTH CENTURY, HAS RESULTED IN PROFOUND CHANGES TO OUR DIET, LIFESTYLE, AND ENVIRONMENT, MANY OF WHICH ARE CAUSAL FACTORS IN THE RISE IN CHRONIC DISEASES. INDUSTRIALIZATION RESULTS IN A NUTRITION TRANSITION FROM AN AGRICULTURAL UNPROCESSED TO A MODERN PROCESSED DIET, INCORPORATING INCREASES IN SUGAR, VEGETABLE OILS, ULTRA-PROCESSED FOODS, LINOLEIC ACID, TRANS-FATS, AND TOTAL ENERGY. THIS DIETARY SHIFT HAS INCURRED NUMEROUS ADVERSE EFFECTS ON METABOLIC AND REPRODUCTIVE HEALTH, CHARACTERIZED BY CHRONIC INFLAMMATION, OXIDATIVE STRESS, AND INSULIN RESISTANCE. MOREOVER, THESE EFFECTS APPEAR TO MULTIPLY ACROSS SUBSEQUENT GENERATIONS VIA EPIGENETIC INHERITANCE. MEN'S FERTILITY IS MARKEDLY AFFECTED BY OBESITY AND DIABETES, WITH AN INCREASE IN TOTAL ENERGY VIA PROCESSED FOOD INTAKE ARGUABLY BEING THE KEY FACTOR DRIVING THE DIABESITY PANDEMIC. IN CONTRAST, WHOLEFOODS RICH IN MICRONUTRIENTS AND PHYTONUTRIENTS SUPPORT MALE FERTILITY AND A HEALTHY BODY WEIGHT. THEREFORE, MEN WANTING TO MAXIMIZE THEIR FERTILITY SHOULD CONSIDER MAKING POSITIVE DIETARY CHANGES, SUCH AS REPLACING PROCESSED FOODS WITH UNPROCESSED FOODS THAT SUPPORT METABOLIC AND REPRODUCTIVE HEALTH. 2023 2 751 35 CARDIOMETABOLIC EFFECTS OF POSTNATAL HIGH-FAT DIET CONSUMPTION IN OFFSPRING EXPOSED TO MATERNAL PROTEIN RESTRICTION IN UTERO. IN RECENT DECADES, THE HIGH INCIDENCE OF INFECTIOUS AND PARASITIC DISEASES HAS BEEN REPLACED BY A HIGH PREVALENCE OF CHRONIC AND DEGENERATIVE DISEASES. CONCOMITANTLY, THERE HAVE BEEN PROFOUND CHANGES IN THE BEHAVIOR AND EATING HABITS OF FAMILIES AROUND THE WORLD, CHARACTERIZING A "NUTRITIONAL TRANSITION" PHENOMENON, WHICH REFERS TO A SHIFT IN DIET IN RESPONSE TO MODERNIZATION, URBANIZATION, OR ECONOMIC DEVELOPMENT FROM UNDERNUTRITION TO THE EXCESSIVE CONSUMPTION OF HYPERCALORIC AND ULTRA-PROCESSED FOODS. PROTEIN MALNUTRITION THAT WAS A HEALTH PROBLEM IN THE FIRST HALF OF THE 20TH CENTURY HAS NOW BEEN REPLACED BY HIGH-FAT DIETS, ESPECIALLY DIETS HIGH IN SATURATED FAT, PREDISPOSING CONSUMERS TO OVERWEIGHT AND OBESITY. THIS PANORAMA POINTS US TO THE ALARMING COEXISTENCE OF BOTH MALNUTRITION AND OBESITY IN THE SAME POPULATION. IN THIS WAY, INDIVIDUALS WHOSE MOTHERS WERE UNDERNOURISHED EARLY IN PREGNANCY AND THEN EXPOSED TO POSTNATAL HYPERLIPIDIC NUTRITION HAVE INCREASED RISK FACTORS FOR DEVELOPING METABOLIC DYSFUNCTION AND CARDIOVASCULAR DISEASES IN ADULTHOOD. THUS, OUR MAJOR AIM WAS TO REVIEW THE CARDIOMETABOLIC EFFECTS RESULTING FROM POSTNATAL HYPERLIPIDIC DIETS IN PROTEIN-RESTRICTED SUBJECTS, AS WELL AS TO EXAMINE THE EPIGENETIC REPERCUSSIONS OCCASIONED BY THE NUTRITIONAL TRANSITION. 2022 3 4803 34 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 4 6088 48 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 5 5089 35 PLACENTAL ADAPTATIONS TO MICRONUTRIENT DYSREGULATION IN THE PROGRAMMING OF CHRONIC DISEASE. POOR NUTRITION DURING PREGNANCY IS KNOWN TO IMPAIR FOETAL DEVELOPMENT AND INCREASE THE RISK OF CHRONIC DISEASE IN OFFSPRING. BOTH MACRONUTRIENTS AND MICRONUTRIENTS ARE REQUIRED FOR A HEALTHY PREGNANCY ALTHOUGH SIGNIFICANTLY LESS IS UNDERSTOOD ABOUT THE ROLE OF MICRONUTRIENTS IN THE PROGRAMMING OF CHRONIC DISEASE. THIS IS DESPITE THE FACT THAT MODERN CALORIE RICH DIETS ARE OFTEN ALSO DEFICIENT IN KEY MICRONUTRIENTS. THE IMPORTANCE OF MICRONUTRIENTS IN GESTATIONAL DISORDERS IS CLEARLY UNDERSTOOD BUT HOW THEY IMPACT LONG TERM DISEASE IN HUMANS REQUIRES FURTHER INVESTIGATION. IN CONTRAST, ANIMAL STUDIES HAVE DEMONSTRATED HOW DIETS HIGH OR LOW IN SPECIFIC MICRONUTRIENTS INFLUENCE OFFSPRING PHYSIOLOGY. MANY OF THESE STUDIES HIGHLIGHT THE IMPORTANCE OF THE PLACENTA IN DETERMINING DISEASE RISK. THIS REVIEW WILL EXPLORE THE EFFECTS OF INDIVIDUAL VITAMINS, MINERALS AND TRACE ELEMENTS ON OFFSPRING DISEASE OUTCOMES AND DISCUSS SEVERAL KEY PLACENTAL ADAPTATIONS THAT ARE AFFECTED BY MULTIPLE MICRONUTRIENTS. THESE PLACENTAL ADAPTATIONS INCLUDE MICRONUTRIENT INDUCED DYSREGULATION OF OXIDATIVE STRESS, ALTERED METHYL DONOR AVAILABILITY AND ITS IMPACT ON EPIGENETIC MECHANISMS AS WELL AS ENDOCRINE DYSFUNCTION. CRITICAL GAPS IN OUR CURRENT KNOWLEDGE AND THE RELATIVE IMPORTANCE OF DIFFERENT MICRONUTRIENTS AT DIFFERENT GESTATIONAL AGES WILL ALSO BE HIGHLIGHTED. FINALLY, THIS REVIEW WILL DISCUSS THE NEED FOR FURTHER STUDIES TO CHARACTERISE THE MICRONUTRIENT STATUS OF AUSTRALIAN WOMEN OF REPRODUCTIVE AGE AND CORRELATE MICRONUTRIENT STATUS TO PLACENTAL ADAPTATIONS, PREGNANCY COMPLICATIONS AND OFFSPRING DISEASE. 2018 6 2584 40 EPIGENETICS OF OBESITY. OBESITY IS A METABOLIC DISEASE, WHICH IS BECOMING AN EPIDEMIC HEALTH PROBLEM: IT HAS BEEN RECENTLY DEFINED IN TERMS OF GLOBAL PANDEMIC. OVER THE YEARS, THE APPROACHES THROUGH FAMILY, TWINS AND ADOPTION STUDIES LED TO THE IDENTIFICATION OF SOME CAUSAL GENES IN MONOGENIC FORMS OF OBESITY BUT THE ORIGINS OF THE PANDEMIC OF OBESITY CANNOT BE CONSIDERED ESSENTIALLY DUE TO GENETIC FACTORS, BECAUSE HUMAN GENOME IS NOT LIKELY TO CHANGE IN JUST A FEW YEARS. EPIGENETIC STUDIES HAVE OFFERED IN RECENT YEARS VALUABLE TOOLS FOR THE UNDERSTANDING OF THE WORLDWIDE SPREAD OF THE PANDEMIC OF OBESITY. THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS-DNA METHYLATION, HISTONE TAILS, AND MIRNAS MODIFICATIONS-IN THE DEVELOPMENT OF OBESITY IS MORE AND MORE EVIDENT. IN THE EPIGENETIC LITERATURE, THERE ARE EVIDENCES THAT THE ENTIRE EMBRYO-FETAL AND PERINATAL PERIOD OF DEVELOPMENT PLAYS A KEY ROLE IN THE PROGRAMMING OF ALL HUMAN ORGANS AND TISSUES. THEREFORE, THE MOLECULAR MECHANISMS INVOLVED IN THE EPIGENETIC PROGRAMMING REQUIRE A NEW AND GENERAL PATHOGENIC PARADIGM, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE THEORY, TO EXPLAIN THE CURRENT EPIDEMIOLOGICAL TRANSITION, THAT IS, THE WORLDWIDE INCREASE OF CHRONIC, DEGENERATIVE, AND INFLAMMATORY DISEASES SUCH AS OBESITY, DIABETES, CARDIOVASCULAR DISEASES, NEURODEGENERATIVE DISEASES, AND CANCER. OBESITY AND ITS RELATED COMPLICATIONS ARE MORE AND MORE ASSOCIATED WITH ENVIRONMENTAL POLLUTANTS (OBESOGENS), GUT MICROBIOTA MODIFICATIONS AND UNBALANCED FOOD INTAKE, WHICH CAN INDUCE, THROUGH EPIGENETIC MECHANISMS, WEIGHT GAIN, AND ALTERED METABOLIC CONSEQUENCES. 2016 7 6873 41 [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 2226 40 EPIGENETIC MODIFICATIONS INDUCED BY NUTRIENTS IN EARLY LIFE PHASES: GENDER DIFFERENCES IN METABOLIC ALTERATION IN ADULTHOOD. METABOLIC CHRONIC DISEASES, ALSO NAMED NONCOMMUNICABLE DISEASES (NCDS), ARE CONSIDERED MULTIFACTORIAL PATHOLOGIES, WHICH ARE DRAMATICALLY INCREASED DURING THE LAST DECADES. NONCOMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASES, OBESITY, DIABETES MELLITUS, CANCERS, AND CHRONIC RESPIRATORY DISEASES MARKEDLY INCREASE MORBIDITY, MORTALITY, AND SOCIOECONOMIC COSTS. MOREOVER, NCDS INDUCE SEVERAL AND COMPLEX CLINICAL MANIFESTATIONS THAT LEAD TO A GRADUAL DETERIORATION OF HEALTH STATUS AND QUALITY OF LIFE OF AFFECTED INDIVIDUALS. MULTIPLE FACTORS ARE INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF THESE DISEASES SUCH AS SEDENTARY BEHAVIOR, SMOKING, POLLUTION, AND UNHEALTHY DIET. INDEED, NUTRITION HAS A PIVOTAL ROLE IN MAINTAINING HEALTH, AND DIETARY IMBALANCES REPRESENT MAJOR DETERMINANTS FAVORING CHRONIC DISEASES THROUGH METABOLIC HOMEOSTASIS ALTERATIONS. IN PARTICULAR, IT APPEARS THAT SPECIFIC NUTRIENTS AND ADEQUATE NUTRITION ARE IMPORTANT IN ALL PERIODS OF LIFE, BUT THEY ARE ESSENTIAL DURING SPECIFIC TIMES IN EARLY LIFE SUCH AS PRENATAL AND POSTNATAL PHASES. INDEED, EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES REPORT THE DELETERIOUS EFFECTS OF AN INCORRECT NUTRITION ON HEALTH STATUS SEVERAL DECADES LATER IN LIFE. DURING THE LAST DECADE, A GROWING INTEREST ON THE POSSIBLE ROLE OF EPIGENETIC MECHANISMS AS LINK BETWEEN NUTRITIONAL IMBALANCES AND NCDS DEVELOPMENT HAS BEEN OBSERVED. FINALLY, BECAUSE OF THE PIVOTAL ROLE OF THE HORMONES IN FAT, CARBOHYDRATE, AND PROTEIN METABOLISM REGULATION THROUGHOUT LIFE, IT IS EXPECTED THAT ANY HORMONAL MODIFICATION OF THESE PROCESSES CAN IMBALANCE METABOLISM AND FAT STORAGE. THEREFORE, A PARTICULAR INTEREST TO SEVERAL CHEMICALS ABLE TO ACT AS ENDOCRINE DISRUPTORS HAS BEEN RECENTLY DEVELOPED. IN THIS REVIEW, WE WILL PROVIDE AN OVERVIEW AND DISCUSS THE EPIGENETIC ROLE OF SOME SPECIFIC NUTRIENTS AND CHEMICALS IN THE MODULATION OF PHYSIOLOGICAL AND PATHOLOGICAL MECHANISMS. 2019 9 3311 47 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 10 4468 38 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 11 2835 40 FOOD AS MEDICINE: TARGETING THE URAEMIC PHENOTYPE IN CHRONIC KIDNEY DISEASE. THE OBSERVATION THAT UNHEALTHY DIETS (THOSE THAT ARE LOW IN WHOLE GRAINS, FRUITS AND VEGETABLES, AND HIGH IN SUGAR, SALT, SATURATED FAT AND ULTRA-PROCESSED FOODS) ARE A MAJOR RISK FACTOR FOR POOR HEALTH OUTCOMES HAS BOOSTED INTEREST IN THE CONCEPT OF 'FOOD AS MEDICINE'. THIS CONCEPT IS ESPECIALLY RELEVANT TO METABOLIC DISEASES, SUCH AS CHRONIC KIDNEY DISEASE (CKD), IN WHICH DIETARY APPROACHES ARE ALREADY USED TO AMELIORATE METABOLIC AND NUTRITIONAL COMPLICATIONS. INCREASED AWARENESS THAT TOXIC URAEMIC METABOLITES ORIGINATE NOT ONLY FROM INTERMEDIARY METABOLISM BUT ALSO FROM GUT MICROBIAL METABOLISM, WHICH IS DIRECTLY INFLUENCED BY DIET, HAS FUELLED INTEREST IN THE POTENTIAL OF 'FOOD AS MEDICINE' APPROACHES IN CKD BEYOND THE CURRENT STRATEGIES OF PROTEIN, SODIUM AND PHOSPHATE RESTRICTION. BIOACTIVE NUTRIENTS CAN ALTER THE COMPOSITION AND METABOLISM OF THE MICROBIOTA, ACT AS MODULATORS OF TRANSCRIPTION FACTORS INVOLVED IN INFLAMMATION AND OXIDATIVE STRESS, MITIGATE MITOCHONDRIAL DYSFUNCTION, ACT AS SENOLYTICS AND IMPACT THE EPIGENOME BY ALTERING ONE-CARBON METABOLISM. AS GUT DYSBIOSIS, INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, PREMATURE AGEING AND EPIGENETIC CHANGES ARE COMMON FEATURES OF CKD, THESE FINDINGS SUGGEST THAT TAILORED, HEALTHY DIETS THAT INCLUDE BIOACTIVE NUTRIENTS AS PART OF THE FOODOME COULD POTENTIALLY BE USED TO PREVENT AND TREAT CKD AND ITS COMPLICATIONS. 2021 12 4804 32 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 13 3707 35 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 14 6426 37 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 15 2881 36 FUTURE PERSPECTIVES OF PERSONALIZED WEIGHT LOSS INTERVENTIONS BASED ON NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA. AS OBESITY HAS BECOME A MAJOR GLOBAL PUBLIC HEALTH CHALLENGE, A LARGE NUMBER OF STUDIES HAVE ANALYZED DIFFERENT STRATEGIES AIMED AT INDUCING A NEGATIVE ENERGY BALANCE AND, CONSEQUENTLY, BODY WEIGHT LOSS. HOWEVER, MOST EXISTING WEIGHT LOSS PROGRAMS ARE GENERALLY UNSUCCESSFUL, SO SEVERAL INTERVENTIONS HAVE BEEN CARRIED OUT TO IDENTIFY PHYSIOLOGIC AND BEHAVIORAL FACTORS CONCERNING THIS VARIABILITY IN ORDER TO IMPLEMENT MORE PERSONALIZED TREATMENT. NOWADAYS, AN INDIVIDUALIZED APPROACH IS BEING PROPOSED THROUGH SO-CALLED PERSONALIZED NUTRITION, WHEREBY NOT ONLY THE PHENOTYPE BUT ALSO THE GENOTYPE IS USED FOR CUSTOMIZED NUTRITION TREATMENT. REGARDING BODY WEIGHT REGULATION, APPROXIMATELY 70 POLYMORPHISMS HAVE BEEN IDENTIFIED IN OR NEAR GENES RELATED TO ENERGY EXPENDITURE, APPETITE, ADIPOGENESIS, INSULIN RESISTANCE, AND LIPID METABOLISM. ALTHOUGH PERSONALIZED NUTRITION REFERS MAINLY TO GENETIC MAKEUP, RECENT ADVANCES IN THE INVESTIGATION OF THE EPIGENOME AND THE MICROBIOME OPEN THE DOOR TO IMPLEMENT MORE PERSONALIZED RECOMMENDATIONS FOR BODY WEIGHT MANAGEMENT. IN THIS CONTEXT, RECENT STUDIES HAVE DEMONSTRATED THE EXISTENCE OF SEVERAL EPIGENETIC MARKERS THAT MAY MODIFY GENE EXPRESSION AND COULD BE INVOLVED IN THE OUTCOME OF WEIGHT LOSS INTERVENTIONS. MOREOVER, DIFFERENT STUDIES HAVE SHOWN THAT DIETARY INTERVENTIONS COULD AFFECT THE COMPOSITION OF GUT MICROBIOTA AND HAVE AN IMPACT ON BODY WEIGHT. THE INTEGRATION OF NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA MAY LEAD TO THE DESIGN OF MORE PERSONALIZED DIETARY TREATMENTS TO PREVENT CHRONIC DISEASES AND TO OPTIMIZE THE INDIVIDUAL'S RESPONSE TO DIETARY INTERVENTIONS. 2015 16 4280 27 MICRONUTRIENTS IN EARLY LIFE AND OFFSPRING METABOLIC HEALTH PROGRAMMING: A PROMISING TARGET FOR PREVENTING NON-COMMUNICABLE DISEASES. CHRONIC NON-COMMUNICABLE DISEASES ARE THE LEADING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. DEVELOPING AND IMPLEMENTING EFFECTIVE PREVENTIVE STRATEGIES IS THE BEST WAY TO ENSURE THE OVERALL METABOLIC HEALTH STATUS OF THE POPULATION AND TO COUNTER THE GLOBAL BURDEN OF NON-COMMUNICABLE DISEASES. PREDISPOSITION TO OBESITY AND OTHER NON-COMMUNICABLE DISEASES IS DUE TO A COMBINATION OF GENETIC AND ENVIRONMENTAL FACTORS THROUGHOUT LIFE, BUT THE EARLY ENVIRONMENT, PARTICULARLY THE ENVIRONMENT DURING THE FETAL PERIOD AND THE EARLY YEARS OF LIFE, IS CRUCIAL IN DETERMINING METABOLIC HEALTH, HENCE THE CONCEPT OF 'FETAL PROGRAMMING'. THE ORIGINS OF THIS CAUSAL LINK BETWEEN ENVIRONMENTAL FACTORS AND DISEASE LIE IN EPIGENETIC MECHANISMS. AMONG THE ENVIRONMENTAL FACTORS, DIET PLAYS A CRUCIAL ROLE IN THIS PROCESS. SUBSTANTIAL EVIDENCE DOCUMENTED THE KEY ROLE OF MACRONUTRIENTS IN THE PROGRAMMING OF METABOLIC DISEASES EARLY IN LIFE. RECENTLY, THE EFFECT OF MATERNAL MICRONUTRIENT INTAKE ON OFFSPRING METABOLIC HEALTH IN LATER LIFE EMERGED. THE PURPOSE OF THIS NARRATIVE REVIEW IS TO BRING TO LIGHT AVAILABLE EVIDENCE IN THE LITERATURE ON THE EFFECT OF MATERNAL MICRONUTRIENT STATUS ON OFFSPRING METABOLIC HEALTH AND UNDERLYING EPIGENETIC MECHANISMS THAT DRIVE THIS LINK TO HIGHLIGHT ITS POTENTIAL ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES. 2023 17 1376 30 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 18 2930 35 GENES AND DIET IN THE PREVENTION OF CHRONIC DISEASES IN FUTURE GENERATIONS. NUTRITION IS A MODIFIABLE KEY FACTOR THAT IS ABLE TO INTERACT WITH BOTH THE GENOME AND EPIGENOME TO INFLUENCE HUMAN HEALTH AND FERTILITY. IN PARTICULAR, SPECIFIC GENETIC VARIANTS CAN INFLUENCE THE RESPONSE TO DIETARY COMPONENTS AND NUTRIENT REQUIREMENTS, AND CONVERSELY, THE DIET ITSELF IS ABLE TO MODULATE GENE EXPRESSION. IN THIS CONTEXT AND THE ERA OF PRECISION MEDICINE, NUTRIGENETIC AND NUTRIGENOMIC STUDIES OFFER SIGNIFICANT OPPORTUNITIES TO IMPROVE THE PREVENTION OF METABOLIC DISTURBANCES, SUCH AS TYPE 2 DIABETES, GESTATIONAL DIABETES, HYPERTENSION, AND CARDIOVASCULAR DISEASES, EVEN WITH TRANSGENERATIONAL EFFECTS. THE PRESENT REVIEW TAKES INTO ACCOUNT THE INTERACTIONS BETWEEN DIET, GENES AND HUMAN HEALTH, AND PROVIDES AN OVERVIEW OF THE ROLE OF NUTRIGENETICS, NUTRIGENOMICS AND EPIGENETICS IN THE PREVENTION OF NON-COMMUNICABLE DISEASES. MOREOVER, WE FOCUS OUR ATTENTION ON THE MECHANISM OF INTERGENERATIONAL OR TRANSGENERATIONAL TRANSMISSION OF THE SUSCEPTIBILITY TO METABOLIC DISTURBANCES, AND UNDERLINE THAT THE REVERSIBILITY OF EPIGENETIC MODIFICATIONS THROUGH DIETARY INTERVENTION COULD COUNTERACT PERTURBATIONS INDUCED BY LIFESTYLE AND ENVIRONMENTAL FACTORS. 2020 19 2157 38 EPIGENETIC MECHANISMS ELICITED BY NUTRITION IN EARLY LIFE. A GROWING NUMBER OF STUDIES FOCUSING ON THE DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASE HYPOTHESIS HAVE IDENTIFIED LINKS AMONG EARLY NUTRITION, EPIGENETIC PROCESSES AND DISEASES ALSO IN LATER LIFE. DIFFERENT EPIGENETIC MECHANISMS ARE ELICITED BY DIETARY FACTORS IN EARLY CRITICAL DEVELOPMENTAL AGES THAT ARE ABLE TO AFFECT THE SUSCEPTIBILITY TO SEVERAL DISEASES IN ADULTHOOD. THE STUDIES HERE REVIEWED SUGGEST THAT MATERNAL AND NEONATAL DIET MAY HAVE LONG-LASTING EFFECTS IN THE DEVELOPMENT OF NON-COMMUNICABLE CHRONIC ADULTHOOD DISEASES, IN PARTICULAR THE COMPONENTS OF THE SO-CALLED METABOLIC SYNDROME, SUCH AS INSULIN RESISTANCE, TYPE 2 DIABETES, OBESITY, DYSLIPIDAEMIA, HYPERTENSION, AND CVD. BOTH MATERNAL UNDER- AND OVER-NUTRITION MAY REGULATE THE EXPRESSION OF GENES INVOLVED IN LIPID AND CARBOHYDRATE METABOLISM. EARLY POSTNATAL NUTRITION MAY ALSO REPRESENT A VITAL DETERMINANT OF ADULT HEALTH BY MAKING AN IMPACT ON THE DEVELOPMENT AND FUNCTION OF GUT MICROBIOTA. AN INADEQUATE GUT MICROBIOTA COMPOSITION AND FUNCTION IN EARLY LIFE SEEMS TO ACCOUNT FOR THE DEVIANT PROGRAMMING OF LATER IMMUNITY AND OVERALL HEALTH STATUS. IN THIS REGARD PROBIOTICS, WHICH HAVE THE POTENTIAL TO RESTORE THE INTESTINAL MICROBIOTA BALANCE, MAY BE EFFECTIVE IN PREVENTING THE DEVELOPMENT OF CHRONIC IMMUNE-MEDIATED DISEASES. MORE RECENTLY, THE EPIGENETIC MECHANISMS ELICITED BY PROBIOTICS THROUGH THE PRODUCTION OF SCFA ARE HYPOTHESISED TO BE THE KEY TO UNDERSTAND HOW THEY MEDIATE THEIR NUMEROUS HEALTH-PROMOTING EFFECTS FROM THE GUT TO THE PERIPHERAL TISSUES. 2011 20 1372 33 DEVELOPMENTAL ORIGINS OF METABOLIC DISEASES. ALMOST 2 BILLION ADULTS IN THE WORLD ARE OVERWEIGHT, AND MORE THAN HALF OF THEM ARE CLASSIFIED AS OBESE, WHILE NEARLY ONE-THIRD OF CHILDREN GLOBALLY EXPERIENCE POOR GROWTH AND DEVELOPMENT. GIVEN THE VAST AMOUNT OF KNOWLEDGE THAT HAS BEEN GLEANED FROM DECADES OF RESEARCH ON GROWTH AND DEVELOPMENT, A NUMBER OF QUESTIONS REMAIN AS TO WHY THE WORLD IS NOW IN THE MIDST OF A GLOBAL EPIDEMIC OF OBESITY ACCOMPANIED BY THE "DOUBLE BURDEN OF MALNUTRITION," WHERE OVERWEIGHT COEXISTS WITH UNDERWEIGHT AND MICRONUTRIENT DEFICIENCIES. THIS CHALLENGE TO THE HUMAN CONDITION CAN BE ATTRIBUTED TO NUTRITIONAL AND ENVIRONMENTAL EXPOSURES DURING PREGNANCY THAT MAY PROGRAM A FETUS TO HAVE A HIGHER RISK OF CHRONIC DISEASES IN ADULTHOOD. TO EXPLORE THIS CONCEPT, FREQUENTLY CALLED THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD), THIS REVIEW CONSIDERS A HOST OF FACTORS AND PHYSIOLOGICAL MECHANISMS THAT DRIVE A FETUS OR CHILD TOWARD A HIGHER RISK OF OBESITY, FATTY LIVER DISEASE, HYPERTENSION, AND/OR TYPE 2 DIABETES (T2D). TO THAT END, THIS REVIEW EXPLORES THE EPIDEMIOLOGY OF DOHAD WITH DISCUSSIONS FOCUSED ON ADAPTATIONS TO HUMAN ENERGETICS, PLACENTAL DEVELOPMENT, DYSMETABOLISM, AND KEY ENVIRONMENTAL EXPOSURES THAT ACT TO PROMOTE CHRONIC DISEASES IN ADULTHOOD. THESE AREAS ARE COMPLEMENTARY AND ADDITIVE IN UNDERSTANDING HOW PROVIDING THE BEST CONDITIONS FOR OPTIMAL GROWTH CAN CREATE THE BEST POSSIBLE CONDITIONS FOR LIFELONG HEALTH. MOREOVER, UNDERSTANDING BOTH PHYSIOLOGICAL AS WELL AS EPIGENETIC AND MOLECULAR MECHANISMS FOR DOHAD IS VITAL TO MOST FULLY ADDRESS THE GLOBAL ISSUES OF OBESITY AND OTHER CHRONIC DISEASES. 2021