1 1412 154 DIETARY PATTERNS INFLUENCE TARGET GENE EXPRESSION THROUGH EMERGING EPIGENETIC MECHANISMS IN NONALCOHOLIC FATTY LIVER DISEASE. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) REFERS TO THE PATHOLOGIC BUILDUP OF EXTRA FAT IN THE FORM OF TRIGLYCERIDES IN LIVER CELLS WITHOUT EXCESSIVE ALCOHOL INTAKE. NAFLD BECAME THE MOST COMMON CAUSE OF CHRONIC LIVER DISEASE THAT IS TIGHTLY ASSOCIATED WITH KEY ASPECTS OF METABOLIC DISORDERS, INCLUDING INSULIN RESISTANCE, OBESITY, DIABETES, AND METABOLIC SYNDROME. IT IS GENERALLY ACCEPTED THAT MULTIPLE MECHANISMS AND PATHWAYS ARE INVOLVED IN THE PATHOGENESIS OF NAFLD. HEREDITY, SEDENTARY LIFESTYLE, WESTERNIZED HIGH SUGAR SATURATED FAT DIET, METABOLIC DERANGEMENTS, AND GUT MICROBIOTA, ALL MAY INTERACT ON A ON GENETICALLY SUSCEPTIBLE INDIVIDUAL TO CAUSE THE DISEASE INITIATION AND PROGRESSION. WHILE THERE IS AN UNQUESTIONABLE ROLE FOR GENE-DIET INTERACTION IN THE ETIOPATHOGENESIS OF NAFLD, IT IS INCREASINGLY APPARENT THAT EPIGENETIC PROCESSES CAN ORCHESTRATE MANY ASPECTS OF THIS INTERACTION AND PROVIDE ADDITIONAL MECHANISTIC INSIGHT. EXCITING RESEARCH DEMONSTRATED THAT EPIGENETIC ALTERATIONS IN CHROMATIN CAN INFLUENCE GENE EXPRESSION CHIEFLY AT THE TRANSCRIPTIONAL LEVEL IN RESPONSE TO UNBALANCED DIET, AND THEREFORE PREDISPOSE AN INDIVIDUAL TO NAFLD. THUS, FURTHER DISCOVERIES INTO MOLECULAR EPIGENETIC MECHANISMS UNDERLYING THE LINK BETWEEN NUTRITION AND ABERRANT HEPATIC GENE EXPRESSION CAN YIELD NEW INSIGHTS INTO THE PATHOGENESIS OF NAFLD, AND ALLOW INNOVATIVE EPIGENETIC-BASED STRATEGIES FOR ITS EARLY PREVENTION AND TARGETED THERAPIES. HEREIN, WE OUTLINE THE CURRENT KNOWLEDGE OF THE INTERACTIVE ROLE OF A HIGH-FAT HIGH-CALORIES DIET AND GENE EXPRESSION THROUGH DNA METHYLATION AND HISTONE MODIFICATIONS ON THE PATHOGENESIS OF NAFLD. WE ALSO PROVIDE PERSPECTIVES ON THE ADVANCEMENT OF THE EPIGENOMICS IN THE FIELD AND POSSIBLE SHORTCOMINGS AND LIMITATIONS AHEAD. 2021 2 74 52 A MULTIDISCIPLINARY APPROACH AND CURRENT PERSPECTIVE OF NONALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW. IN RECENT TIMES, NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BEEN CONSIDERED ONE OF THE MAJOR CAUSES OF LIVER DISEASE ACROSS THE WORLD. NAFLD IS DEFINED AS THE DEPOSITION OF TRIGLYCERIDES IN THE LIVER AND IS ASSOCIATED WITH OBESITY AND METABOLIC SYNDROME. HYPERINSULINEMIA, INSULIN RESISTANCE (IR), FATTY LIVER, HEPATOCYTE INJURY, UNBALANCED PROINFLAMMATORY CYTOKINES, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, LIVER INFLAMMATION, AND FIBROSIS ARE THE MAIN PATHOGENESIS IN NAFLD. RECENT STUDIES SUGGEST THAT THE ACTION OF INTESTINAL MICROBIOTA THROUGH CHRONIC INFLAMMATION, INCREASED INTESTINAL PERMEABILITY, AND ENERGY UPTAKE PLAYS A VITAL ROLE IN NAFLD. MOREOVER, POLYCYSTIC OVARIAN SYNDROME ALSO CAUSES NAFLD DEVELOPMENT THROUGH IR. AGE, GENDER, RACE, ETHNICITY, SLEEP, DIET, SEDENTARY LIFESTYLE, AND GENETIC AND EPIGENETIC PATHWAYS ARE SOME CONTRIBUTING FACTORS OF NAFLD THAT CAN EXACERBATE THE RISK OF LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA (HCC) AND EVENTUALLY LEAD TO DEATH. NAFLD HAS VARIOUS PRESENTATIONS, INCLUDING FATIGUE, UNEXPLAINED WEIGHT LOSS, BLOATING, UPPER ABDOMINAL PAIN, DECREASED APPETITE, HEADACHE, ANXIETY, POOR SLEEP, INCREASED THIRST, PALPITATION, AND A FEELING OF WARMTH. SOME STUDIES HAVE SHOWN THAT NAFLD WITH SEVERE CORONAVIRUS DISEASE 2019 (COVID-19) HAS POOR OUTCOMES. THE GOLD STANDARD FOR NAFLD DIAGNOSIS IS LIVER BIOPSY. OTHER DIAGNOSTIC TOOLS ARE IMAGING TESTS, SERUM BIOMARKERS, MICROBIOTA MARKERS, AND TESTS FOR EXTRAHEPATIC COMPLICATIONS. THERE ARE NO SPECIFIC TREATMENTS FOR NAFLD. THEREFORE, THE MAIN CONCERN FOR NAFLD IS TREATING THE COMORBID CONDITIONS SUCH AS ANTI-DIABETIC AGENTS FOR TYPE 2 DIABETES MELLITUS, STATINS TO REDUCE HCC PROGRESSION, ANTIOXIDANTS TO PREVENT HEPATOCELLULAR DAMAGE, AND BARIATRIC SURGERY FOR PATIENTS WITH A BMI OF >40 KG/M(2) AND >35 KG/M(2) WITH COMORBIDITIES. LIFESTYLE AND DIETARY CHANGES ARE CONSIDERED PREVENTIVE STRATEGIES AGAINST NAFLD ADVANCEMENT. INADEQUATE TREATMENT OF NAFLD FURTHER LEADS TO CARDIAC CONSEQUENCES, SLEEP APNEA, CHRONIC KIDNEY DISEASE, AND INFLAMMATORY BOWEL DISEASE. IN THIS SYSTEMATIC REVIEW, WE HAVE BRIEFLY DISCUSSED THE RISK FACTORS, PATHOGENESIS, CLINICAL FEATURES, AND NUMEROUS CONSEQUENCES OF NAFLD. WE HAVE ALSO REVIEWED VARIOUS GUIDELINES FOR NAFLD DIAGNOSIS ALONG WITH EXISTING THERAPEUTIC STRATEGIES FOR THE MANAGEMENT AND PREVENTION OF THE DISEASE. 2022 3 4711 46 NON-ALCOHOLIC FATTY LIVER DISEASE IN OBESE CHILDREN AND ADOLESCENTS: A ROLE FOR NUTRITION? NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BECOME THE MOST COMMON CAUSE OF CHRONIC LIVER DISEASE IN CHILDREN, PARALLELING THE INCREASING PREVALENCE OF OBESITY WORLDWIDE. THE PATHOGENESIS OF PAEDIATRIC NAFLD IS NOT FULLY UNDERSTOOD, BUT IT IS KNOWN THAT OBESITY, NUTRITION, LIFESTYLE VARIABLES, GENETIC AND EPIGENETIC FACTORS MAY BE CAUSALLY INVOLVED IN THE DEVELOPMENT OF THIS COMMON METABOLIC LIVER DISEASE. IN PARTICULAR, OBESITY AND NUTRITION ARE AMONG THE STRONGEST RISK FACTORS FOR PAEDIATRIC NAFLD, WHICH MAY EXERT THEIR ADVERSE HEPATIC EFFECTS ALREADY BEFORE BIRTH. EXCESS ENERGY INTAKE INDUCES HYPERTROPHY AND HYPERPLASIA OF ADIPOSE TISSUE WITH SUBSEQUENT DEVELOPMENT OF SYSTEMIC INSULIN RESISTANCE, WHICH IS ANOTHER IMPORTANT RISK FACTOR FOR NAFLD. DIET COMPOSITION AND IN PARTICULAR SIMPLE CARBOHYDRATE INTAKE (ESPECIALLY HIGH FRUCTOSE INTAKE) MAY PROMOTE THE DEVELOPMENT OF NAFLD, WHEREAS NON-DIGESTIBLE CARBOHYDRATES (DIETARY FIBER), BY AFFECTING GUT MICROBIOTA, MAY FAVOUR THE INTEGRITY OF GUT WALL AND REDUCE INFLAMMATION, OPPOSING THIS PROCESS. SATURATED FAT INTAKE MAY ALSO PROMOTE NAFLD DEVELOPMENT, WHEREAS UNSATURATED FAT INTAKE HAS SOME BENEFICIAL EFFECTS. PROTEIN INTAKE DOES NOT SEEM TO AFFECT THE DEVELOPMENT OF NAFLD, BUT FURTHER INVESTIGATION IS NEEDED. IN CONCLUSION, LIFESTYLE MODIFICATIONS TO INDUCE WEIGHT LOSS, THROUGH DIET AND PHYSICAL ACTIVITY, REMAIN THE MAINSTAY OF TREATMENT FOR PAEDIATRIC NAFLD. THE USE OF DIETARY SUPPLEMENTS, SUCH AS OMEGA-3 FATTY ACIDS AND PROBIOTICS, NEEDS FURTHER STUDY BEFORE RECOMMENDATION. 2022 4 4795 45 NUTRITIONAL GENOMICS IN NONALCOHOLIC FATTY LIVER DISEASE. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A COMMON CHRONIC CONDITION ASSOCIATED WITH GENETIC AND ENVIRONMENTAL FACTORS IN WHICH FAT ABNORMALLY ACCUMULATES IN THE LIVER. NAFLD IS EPIDEMIOLOGICALLY ASSOCIATED WITH OBESITY, TYPE 2 DIABETES, AND DYSLIPIDEMIA. ENVIRONMENTAL FACTORS, SUCH AS PHYSICAL INACTIVITY AND AN UNBALANCED DIET, INTERACT WITH GENETIC FACTORS, SUCH AS EPIGENETIC MECHANISMS AND POLYMORPHISMS FOR THE GENESIS AND DEVELOPMENT OF THE CONDITION. DIFFERENT GENETIC POLYMORPHISMS SEEM TO BE INVOLVED IN THIS CONTEXT, INCLUDING VARIANTS IN PNPLA3, TM6SF2, PEMT, AND CHDH GENES, PLAYING A ROLE IN THE DISEASE'S SUSCEPTIBILITY, DEVELOPMENT, AND SEVERITY. FROM CARBOHYDRATE INTAKE AND WEIGHT LOSS TO OMEGA-3 SUPPLEMENTATION AND CALORIC RESTRICTION, DIFFERENT DIETARY AND NUTRITIONAL FACTORS APPEAR TO BE INVOLVED IN CONTROLLING THE ONSET AND PROGRESSION OF NAFLD CONDITIONS INFLUENCING METABOLISM, GENE, AND PROTEIN EXPRESSION. THE POLYGENIC RISK SCORE REPRESENTS A SUM OF TRAIT-ASSOCIATED ALLELES CARRIED BY AN INDIVIDUAL AND SEEMS TO BE ASSOCIATED WITH NAFLD OUTCOMES DEPENDING ON THE DIETARY CONTEXT. UNDERSTANDING THE EXACT EXTENT TO WHICH LIFESTYLE INTERVENTIONS AND GENETIC PREDISPOSITIONS CAN PLAY A ROLE IN THE PREVENTION AND MANAGEMENT OF NAFLD CAN BE CRUCIAL FOR THE ESTABLISHMENT OF A PERSONALIZED AND INTEGRATIVE APPROACH TO PATIENTS. 2023 5 6861 39 [OBESITY: A MODEL OF COMPLEX INTERACTIONS BETWEEN GENETICS AND ENVIRONMENT]. OBESITY IS EXPLAINED BY THE JOINT ACTIONS OF GENETIC SUSCEPTIBILITY AND ENVIRONMENTAL FACTORS, SUCH AS A WESTERNIZED LIFESTYLE (SEDENTARY LIFESTYLE, CALORIE-DENSE FOODS), INDUCING AN OBESOGENIC ENVIRONMENT. THE SEARCH FOR OBESITY SUSCEPTIBILITY GENES REMAINS COMPLEX, DESPITE RECENT ADAVANCES MADE IN THE OBESITY GENETICS FIELD. EXCEPT VERY RARE MONOGENIC TYPE OBESITY, COMMON OBESITY IS THOUGHT TO BE POLYGENIC AND THE GENETIC CONTRIBUTION TO INTERINDIVIDUAL VARIATION IN COMMON OBESITY HAS BEEN ESTIMATED AT 40-70 %. THE GENOME-WIDE ASSOCIATION STUDIES HAVE LED TO IDENTIFY NUMEROUS GENETIC LOCI ASSOCIATED WITH BODY MASS INDEX AND OBESITY RISK. HOWEVER, THE PREDICTIVE VALUE OF THESE LOCI TO THE OBESITY RISK AT THE POPULATION LEVEL REMAINS LOW. FINALLY, THE INFLUENCE OF ENVIRONMENTAL FACTORS ON GENETIC SUSCEPTIBILITY TO WEIGHT GAIN IS ALSO RELATED TO EPIGENETIC FACTORS. NUTRITIONAL UNBALANCE DURING FETAL DEVELOPMENT MAY CHANGE THE INTRAUTERINE ENVIRONMENT AND LEAD TO ALTERED GENE EXPRESSION (FETAL PROGRAMMING) WITH ALTERATIONS IN DNA OR HISTONE METHYLATION RESULTING IN AN INCREASED SUSCEPTIBILITY TO CHRONIC DISEASE IN ADULTHOOD, SUCH AS OBESITY. 2012 6 1939 44 EPIDEMIOLOGY AND (PATHO)PHYSIOLOGY OF FOLIC ACID SUPPLEMENT USE IN OBESE WOMEN BEFORE AND DURING PREGNANCY. PRECONCEPTION FOLIC ACID SUPPLEMENT USE IS A WELL-KNOWN METHOD OF PRIMARY PREVENTION OF NEURAL TUBE DEFECTS (NTDS). OBESE WOMEN ARE AT A HIGHER RISK FOR HAVING A CHILD WITH A NTD. AS DIFFERENT INTERNATIONAL RECOMMENDATIONS ON FOLIC ACID SUPPLEMENT USE FOR OBESE WOMEN BEFORE AND DURING PREGNANCY EXIST, THIS NARRATIVE REVIEW PROVIDES AN OVERVIEW OF EPIDEMIOLOGY OF FOLATE DEFICIENCY IN OBESE (PRE)PREGNANT WOMEN, ELABORATES ON POTENTIAL MECHANISMS UNDERLYING FOLATE DEFICIENCY, AND DISCUSSES CONSIDERATIONS FOR THE USAGE OF HIGHER DOSES OF FOLIC ACID SUPPLEMENTS. WOMEN WITH OBESITY MORE OFTEN SUFFER FROM AN ABSOLUTE FOLATE DEFICIENCY, AS THEY ARE LESS COMPLIANT TO PERICONCEPTIONAL FOLIC ACID SUPPLEMENT USE RECOMMENDATIONS. IN ADDITION, THEIR DIETARY FOLATE INTAKE IS LIMITED DUE TO AN UNBALANCED DIET (RELATIVE MALNUTRITION). THE ASSOCIATION OF OBESITY AND NTDS ALSO SEEMS TO BE INDEPENDENT OF FOLATE INTAKE, WITH STUDIES SUGGESTING AN INCREASED NEED OF FOLATE (RELATIVE DEFICIENCY) DUE TO DERANGEMENTS INVOLVED IN OTHER PATHWAYS. THE RELATIVE FOLATE DEFICIENCY, AS A RESULT OF AN INCREASED METABOLIC NEED FOR FOLATE IN OBESE WOMEN, CAN BE DUE TO: (1) LOW-GRADE CHRONIC INFLAMMATION (2) INSULIN RESISTANCE, (3) INOSITOL, AND (4) DYSBIOTIC GUT MICROBIOME, WHICH PLAYS A ROLE IN FOLATE PRODUCTION AND UPTAKE. IN ALL THESE PATHWAYS, THE FOLATE-DEPENDENT ONE-CARBON METABOLISM IS INVOLVED. IN CONCLUSION, SCIENTIFIC EVIDENCE OF THE INVOLVEMENT OF SEVERAL FOLATE-RELATED PATHWAYS IMPLIES TO INCREASE THE RECOMMENDED FOLIC ACID SUPPLEMENTATION IN OBESE WOMEN. HOWEVER, THE PHYSIOLOGICAL UPTAKE OF SYNTHETIC FOLIC ACID IS LIMITED AND SIDE-EFFECTS OF UNMETABOLIZED FOLIC ACID IN MOTHERS AND OFFSPRING, IN PARTICULAR VARIATIONS IN EPIGENETIC (RE)PROGRAMMING WITH LONG-TERM HEALTH EFFECTS, CANNOT BE EXCLUDED. THEREFORE, WE EMPHASIZE ON THE URGENT NEED FOR FURTHER RESEARCH AND PRECONCEPTION PERSONALIZED COUNSELING ON FOLATE STATUS, LIFESTYLE, AND MEDICAL CONDITIONS. 2021 7 4586 41 NAFLD AT THE INTERFACE OF THE MOTHER-INFANT DYAD. THIS REVIEW AIMS TO FOCUS THE LINKS EXISTING BETWEEN SEVERAL ASPECTS OF THE MOTHER-CHILD DYAD IN THE INTRICATE PLAYGROUND OF OBESITY AND METABOLIC SYNDROME (METS), INCLUDING ITS HEPATIC COMPONENT, THE NON- ALCOHOLIC FATTY LIVER DISEASE (NAFLD). IN RECENT YEARS HUMAN AND ANIMAL MODEL STUDIES HAVE SHOWN THAT DIETARY INTERVENTIONS IN MOTHERS AND OFFSPRING CAN BE SUCCESSFUL IN REDUCING THE RISK OF NAFLD DEVELOPMENT. EVIDENCES ALSO CONCERN THE NEW CONCEPT OF A REAL INTERGENERATIONAL TRANSMISSION OF PREDISPOSITION TO METABOLIC DISORDERS. CERTAIN GENES, SUCH AS SIRT1 AND PNPLA3, AND SOME EPIGENETIC MODIFICATIONS, INCLUDING MICRO RNAS FUNCTION, SEEM TO BE RESPONSIBLE FOR FETAL REPROGRAMMING IN THE SETTING OF MATERNAL OBESITY. THESE MODIFIERS APPEAR TO BE POTENTIAL THERAPEUTIC TARGETS TO REDUCE THE RISK OF FUTURE METABOLIC DYSFUNCTIONS. CONTROLLING ANTEPARTUM HYPERGLYCEMIA, PREVENTING GESTATIONAL DIABETES, AND AVOIDING EXCESSIVE WEIGHT GAIN DURING PREGNANCY CAN HELP REDUCE THE RELENTLESS EPIDEMIC OF CHILDHOOD OBESITY AND NAFLD. ALSO, THE COMPOSITION OF THE INTESTINAL MICROBIOTA SEEMS TO BE RELATED TO THE DEVELOPMENT OF METABOLIC DISORDERS IN THE OFFSPRING. SEVERAL STUDIES SHOW THAT BREASTFED INFANTS HAVE A MICROBIAL SIGNATURE DIFFERENT FROM FORMULA-FED INFANTS. MUCH INTERESTINGLY, PROLONGED BREASTFEEDING IS BENEFICIAL NOT ONLY FOR THE NEWBORN AND HIS HEALTH IN ADULT LIFE, BUT ALSO FOR THE MOTHERS' HEALTH. MATERNAL BENEFITS INCLUDE REDUCING THE RISK OF DEVELOPING CHRONIC DISEASES, SUCH AS DIABETES MELLITUS, MYOCARDIAL INFARCTION AND NAFLD AS WELL. IN CONCLUSION, ALL ABOVE MECHANISMS APPEAR TO INTERVENE SYNERGISTICALLY AND MAY ACT AS MODIFIABLE RISK FACTORS FOR INFANT AND MOTHER NAFLD. 2020 8 2699 44 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 9 4464 39 MOLECULAR MECHANISMS OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)/NONALCOHOLIC STEATOHEPATITIS (NASH). NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ONE OF THE MOST COMMON CHRONIC LIVER DISEASES WORLDWIDE AND HAS GARNERED INCREASING ATTENTION IN RECENT DECADES. NAFLD IS CHARACTERIZED BY A WIDE RANGE OF LIVER CHANGES, FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS (NASH), CIRRHOSIS, AND HEPATOCELLULAR CARCINOMA. THE PATHOGENESIS OF NAFLD/NASH IS VERY COMPLICATED AND INVOLVES LIPID ACCUMULATION, INSULIN RESISTANCE, INFLAMMATION, AND FIBROGENESIS. IN ADDITION, NAFLD IS CLOSELY ASSOCIATED WITH COMPLICATIONS SUCH AS OBESITY, DYSLIPIDEMIA, AND TYPE 2 DIABETES. IN PARTICULAR, THE CLINICAL SPECTRUM, PATHOPHYSIOLOGY, AND THERAPEUTIC OPTIONS OF NAFLD SHARE MANY THINGS IN COMMON WITH DIABETES. INSULIN RESISTANCE IS AN UNDERLYING BASIS FOR THE PATHOGENESIS OF DIABETES AND NAFLD. THIS CHAPTER FOCUSES ON THE MOLECULAR MECHANISM INVOLVED IN THE PATHOGENESIS OF INSULIN RESISTANCE, DIABETES, AND NASH/NAFLD INCLUDING THOSE THAT DRIVE DISEASE PROGRESSION SUCH AS OXIDATIVE STRESS, GENETIC AND EPIGENETIC MECHANISMS, ADIPONECTIN, CYTOKINES, AND IMMUNE CELLS. 2021 10 4205 52 METABOLO-EPIGENETIC INTERPLAY PROVIDES TARGETED NUTRITIONAL INTERVENTIONS IN CHRONIC DISEASES AND AGEING. EPIGENETIC MODIFICATIONS ARE CHEMICAL MODIFICATIONS THAT AFFECT GENE EXPRESSION WITHOUT ALTERING DNA SEQUENCES. IN PARTICULAR, EPIGENETIC CHEMICAL MODIFICATIONS CAN OCCUR ON HISTONE PROTEINS -MAINLY ACETYLATION, METHYLATION-, AND ON DNA AND RNA MOLECULES -MAINLY METHYLATION-. ADDITIONAL MECHANISMS, SUCH AS RNA-MEDIATED REGULATION OF GENE EXPRESSION AND DETERMINANTS OF THE GENOMIC ARCHITECTURE CAN ALSO AFFECT GENE EXPRESSION. IMPORTANTLY, DEPENDING ON THE CELLULAR CONTEXT AND ENVIRONMENT, EPIGENETIC PROCESSES CAN DRIVE DEVELOPMENTAL PROGRAMS AS WELL AS FUNCTIONAL PLASTICITY. HOWEVER, MISBALANCED EPIGENETIC REGULATION CAN RESULT IN DISEASE, PARTICULARLY IN THE CONTEXT OF METABOLIC DISEASES, CANCER, AND AGEING. NON-COMMUNICABLE CHRONIC DISEASES (NCCD) AND AGEING SHARE COMMON FEATURES INCLUDING ALTERED METABOLISM, SYSTEMIC META-INFLAMMATION, DYSFUNCTIONAL IMMUNE SYSTEM RESPONSES, AND OXIDATIVE STRESS, AMONG OTHERS. IN THIS SCENARIO, UNBALANCED DIETS, SUCH AS HIGH SUGAR AND HIGH SATURATED FATTY ACIDS CONSUMPTION, TOGETHER WITH SEDENTARY HABITS, ARE RISK FACTORS IMPLICATED IN THE DEVELOPMENT OF NCCD AND PREMATURE AGEING. THE NUTRITIONAL AND METABOLIC STATUS OF INDIVIDUALS INTERACT WITH EPIGENETICS AT DIFFERENT LEVELS. THUS, IT IS CRUCIAL TO UNDERSTAND HOW WE CAN MODULATE EPIGENETIC MARKS THROUGH BOTH LIFESTYLE HABITS AND TARGETED CLINICAL INTERVENTIONS -INCLUDING FASTING MIMICKING DIETS, NUTRACEUTICALS, AND BIOACTIVE COMPOUNDS- WHICH WILL CONTRIBUTE TO RESTORE THE METABOLIC HOMEOSTASIS IN NCCD. HERE, WE FIRST DESCRIBE KEY METABOLITES FROM CELLULAR METABOLIC PATHWAYS USED AS SUBSTRATES TO "WRITE" THE EPIGENETIC MARKS; AND COFACTORS THAT MODULATE THE ACTIVITY OF THE EPIGENETIC ENZYMES; THEN, WE BRIEFLY SHOW HOW METABOLIC AND EPIGENETIC IMBALANCES MAY RESULT IN DISEASE; AND, FINALLY, WE SHOW SEVERAL EXAMPLES OF NUTRITIONAL INTERVENTIONS - DIET BASED INTERVENTIONS, BIOACTIVE COMPOUNDS, AND NUTRACEUTICALS- AND EXERCISE TO COUNTERACT EPIGENETIC ALTERATIONS. 2023 11 615 42 BIOACTIVE COMPONENTS AND POSSIBLE ACTIVITIES OF MEDICINAL MUSHROOMS IN ALLEVIATING THE PATHOGENESIS OF NONALCOHOLIC FATTY LIVER DISEASE (REVIEW). NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A GLOBAL DISEASE THAT IS CLOSELY ASSOCIATED WITH OBESITY, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE. EXCESSIVE FAT ACCUMULATION, FATTY DEGENERATION, AND CHRONIC INFLAMMATION OF THE LIVER ACTIVATE THE PROGRESSION OF NAFLD FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS AND FURTHER TO LIVER FIBROSIS, CIRRHOSIS, AND HEPATOCELLULAR CARCINOMA. THE UNDERLYING MECHANISM FOR THE DEVELOPMENT AND PROGRESSION OF NAFLD IS COMPLEX AND A MULTIPLE-HIT HYPOTHESIS INCLUDING DIETARY, ENVIRONMENTAL, GENETIC, AND EPIGENETIC FACTORS HAS BEEN RAISED. INCREASED DE NOVO LIPOGENESIS, DECREASED LIPOLYSIS, AND INSULIN RESISTANCE ARE ASSOCIATED WITH THE DEVELOPMENT OF NAFLD. CURRENTLY, NO EFFECTIVE DRUG THERAPIES ARE APPROVED FOR THE TREATMENT OF NAFLD. SEVERAL MEDICINAL MUSHROOMS HAVE BEEN FOUND TO HAVE SIGNIFICANT WEIGHT CONTROL AND GUT MICROBE MODULATION ACTIVITIES AND ANTIHYPERTRIGLYCERIDEMIC, ANTIHYPERGLYCEMIC, ANTIOXIDANT, AND ANTI-INFLAMMATORY EFFECTS, WHICH MAY BE USEFUL TO PREVENT AND ATTENUATE THE DEVELOPMENT AND PROGRESSION OF NAFLD. THESE BENEFICIAL EFFECTS ARE ASSOCIATED WITH MUSHROOMS' BIOACTIVE COMPONENTS, SUCH AS POLYSACCHARIDES, DIETARY FIBERS, ANTIOXIDANTS, AND OTHER COMPOUNDS DERIVED FROM FRUITING BODIES, CULTURED MYCELIUM, AND/OR BROTH OF MEDICINAL MUSHROOMS. THIS ARTICLE PRESENTS AN OVERVIEW OF MULTIPLE ASPECTS OF NAFLD, INCLUDING THE EPIDEMIOLOGY, PATHOGENESIS, MANAGEMENT, AND TREATMENT. THE BIOACTIVE COMPONENTS AND POSSIBLE ACTIVITIES OF MEDICINAL MUSHROOMS IN ALLEVIATING THE PATHOGENESIS OF NAFLD ARE ALSO REVIEWED. 2021 12 5079 52 PHYSIOPATHOLOGY OF NONALCOHOLIC FATTY LIVER DISEASE: FROM DIET TO NUTRIGENOMICS. PURPOSE OF REVIEW: NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS THE MOST COMMON CAUSE OF CHRONIC LIVER DISEASE WORLDWIDE AND IS STRONGLY ASSOCIATED WITH METABOLIC DISORDERS, SUCH AS OBESITY, TYPE 2 DIABETES MELLITUS, AND METABOLIC SYNDROME, TO THE EXTENT THAT A NEW DEFINITION OF METABOLIC ASSOCIATED FATTY LIVER DISEASE HAS BEEN PROPOSED. RECENT FINDINGS: INSULIN RESISTANCE, WORSENED BY A HIGH-FAT AND HIGH-CARBOHYDRATE DIET, IS THE KEY TO THE PHYSIOPATHOLOGY OF HEPATIC STEATOSIS. THIS IS DRIVEN BY SEVERAL MECHANISMS THAT ARE MOSTLY ACTIVATED AT A GENETIC LEVEL, SUCH AS DE-NOVO LIPOGENESIS AND TRIGLYCERIDE SYNTHESIS. THEREFORE, MANY DIET REGIMENS HAVE BEEN STUDIED, ALTHOUGH SIGNIFICANT CONTROVERSIES REMAIN REGARDING THEIR METABOLIC EFFECTS AND LONG-TERM SUSTAINABILITY. SUMMARY: IN THIS REVIEW, WE SUMMARIZED THE ROLE AND EFFECTS OF THE MAIN MACRONUTRIENTS ON THE DEVELOPMENT OF NAFLD AND DISCUSSED THE MOLECULAR MECHANISMS INVOLVED. WE ALSO DISCUSSED THE IMPORTANCE OF GENETIC POLYMORPHISMS, EPIGENETIC ALTERATIONS, AND DYSBIOSIS TO DETERMINE IF LIFESTYLE MODIFICATION AND A SPECIFIC DIETARY REGIMEN COULD BE AN ESSENTIAL PART OF NAFLD TREATMENT. 2022 13 6873 39 [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 14 4188 51 METABOLIC ASSOCIATED FATTY LIVER DISEASE IN CHILDREN AND ADOLESCENTS: MECHANISMS OF A SILENT EPIDEMIC AND THERAPEUTIC OPTIONS. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS NOW IDENTIFIED AS A HEPATIC SIGN OF METABOLIC SYNDROME AND IS THE MOST FREQUENT CAUSE OF CHRONIC LIVER DISEASE IN ALL AGES. IT IS ASSUMED THAT A GENETIC PREDISPOSITION ASSOCIATED WITH EPIGENETIC FACTORS PARTICIPATES IN THE EVOLUTION OF THIS CONDITION. VISCERAL OBESITY AND INSULIN RESISTANCE (IR) HAVE ALWAYS BEEN CONSIDERED THE MOST IMPORTANT CAUSATIVE FACTORS OF METABOLIC SYNDROME (METS) AND NAFLD, BUT CURRENTLY, THE INTERACTION BETWEEN GENETIC HERITAGE AND ENVIRONMENTAL FACTORS IS INCREASINGLY CONSIDERED FUNDAMENTAL IN THE GENESIS OF METABOLIC DISORDERS ASSOCIATED WITH NAFLD. IN FACT, IN PATIENTS WITH NAFLD, INSULIN RESISTANCE, ARTERIAL HYPERTENSION, ABDOMINAL OBESITY, DYSLIPIDEMIA AND REDUCED INTESTINAL PERMEABILITY HAVE OFTEN BEEN FOUND, AS WELL AS A HIGHER PREVALENCE OF CORONARY ARTERY DISEASE, OBSTRUCTIVE SLEEP APNEA, POLYCYSTIC OVARY SYNDROME AND OSTEOPENIA, WHICH DEFINE A METS FRAMEWORK. EARLY DIAGNOSIS IS NEEDED TO PREVENT DISEASE PROGRESSION THROUGH PRIMARILY LIFESTYLE INTERVENTIONS. UNFORTUNATELY, AT PRESENT, THERE ARE NO MOLECULES RECOMMENDED FOR PEDIATRIC PATIENTS. HOWEVER, SEVERAL NEW DRUGS ARE IN CLINICAL TRIALS. FOR THIS REASON, TARGETED STUDIES ON THE INTERACTION BETWEEN GENETICS AND ENVIRONMENTAL FACTORS INVOLVED IN THE DEVELOPMENT OF NAFLD AND METS AND ON THE PATHOGENETIC MECHANISMS THAT DETERMINE THE EVOLUTION IN NON-ALCOHOLIC STEATOHEPATITIS (NASH), SHOULD BE IMPLEMENTED. THEREFORE, IT IS DESIRABLE THAT FUTURE STUDIES MAY BE USEFUL IN IDENTIFYING PATIENTS AT RISK OF DEVELOPING NAFLD AND METS EARLY. 2023 15 2584 41 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 16 4080 23 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 17 3408 38 HOW WESTERN DIET AND LIFESTYLE DRIVE THE PANDEMIC OF OBESITY AND CIVILIZATION DISEASES. WESTERNIZED POPULATIONS ARE PLAGUED BY A PLETHORA OF CHRONIC NON-INFECTIOUS DEGENERATIVE DISEASES, TERMED AS "CIVILIZATION DISEASES", LIKE OBESITY, DIABETES, CARDIOVASCULAR DISEASES, CANCER, AUTOIMMUNE DISEASES, ALZHEIMER'S DISEASE AND MANY MORE, DISEASES WHICH ARE RARE OR VIRTUALLY ABSENT IN HUNTER-GATHERERS AND OTHER NON-WESTERNIZED POPULATIONS. THERE IS A GROWING AWARENESS THAT THE CAUSE OF THIS AMAZING DISCREPANCY LIES IN THE PROFOUND CHANGES IN DIET AND LIFESTYLE DURING RECENT HUMAN HISTORY. THIS PAPER SHOWS THAT THE TRANSITION FROM PALEOLITHIC NUTRITION TO WESTERN DIETS, ALONG WITH LACK OF CORRESPONDING GENETIC ADAPTATIONS, CAUSE SIGNIFICANT DISTORTIONS OF THE FINE-TUNED METABOLISM THAT HAS EVOLVED OVER MILLIONS OF YEARS OF HUMAN EVOLUTION IN ADAPTATION TO PALEOLITHIC DIETS. WITH THE INCREASING SPREAD OF WESTERN DIET AND LIFESTYLE WORLDWIDE, OVERWEIGHT AND CIVILIZATION DISEASES ARE ALSO RAPIDLY INCREASING IN DEVELOPING COUNTRIES. IT IS SUGGESTED THAT THE DIET-RELATED KEY CHANGES IN THE DEVELOPMENTAL PROCESS INCLUDE AN INCREASED PRODUCTION OF REACTIVE OXYGEN SPECIES AND OXIDATIVE STRESS, DEVELOPMENT OF HYPERINSULINEMIA AND INSULIN RESISTANCE, LOW-GRADE INFLAMMATION AND AN ABNORMAL ACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM AND THE RENIN-ANGIOTENSIN SYSTEM, ALL OF WHICH PLAY PIVOTAL ROLES IN THE DEVELOPMENT OF DISEASES OF CIVILIZATION. IN ADDITION, DIET-RELATED EPIGENETIC CHANGES AND FETAL PROGRAMMING PLAY AN IMPORTANT ROLE. THE SUGGESTED PATHOMECHANISM IS ALSO ABLE TO EXPLAIN THE WELL-KNOWN BUT NOT COMPLETELY UNDERSTOOD CLOSE RELATIONSHIP BETWEEN OBESITY AND THE WIDE RANGE OF COMORBIDITIES, LIKE TYPE 2 DIABETES MELLITUS, CARDIOVASCULAR DISEASE, ETC., AS DISEASES OF THE SAME ETIOPATHOLOGY. CHANGING OUR LIFESTYLE IN ACCORDANCE WITH OUR GENETIC MAKEUP, INCLUDING DIET AND PHYSICAL ACTIVITY, MAY HELP PREVENT OR LIMIT THE DEVELOPMENT OF THESE DISEASES. 2019 18 44 53 A COMPREHENSIVE REVIEW ON HIGH -FAT DIET-INDUCED DIABETES MELLITUS: AN EPIGENETIC VIEW. MODERN LIFESTYLE, GENETICS, NUTRITIONAL OVERLOAD THROUGH HIGH-FAT DIET ATTRIBUTED PREVALENCE AND DIABETES OUTCOMES WITH VARIOUS COMPLICATIONS PRIMARILY DUE TO OBESITY IN WHICH ENERGY-DENSE DIETS FREQUENTLY AFFECT METABOLIC HEALTH. ONE POSSIBLE ISSUE USUALLY ASSOCIATED WITH ELEVATED CHRONIC FAT INTAKE IS INSULIN RESISTANCE, AND HYPERGLYCEMIA CONSTITUTES AN IMPORTANT FUNCTION IN ALTERING THE CARBOHYDRATES AND LIPIDS METABOLISM. SIMILARLY, IN ASSESSING HUMAN SUSCEPTIBILITY TO WEIGHT GAIN AND OBESITY, GENETIC VARIATIONS PLAY A CENTRAL ROLE, CONTRIBUTING TO KEEN INTEREST IN IDENTIFYING THE POSSIBLE ROLE OF EPIGENETICS AS A MEDIATOR OF GENE-ENVIRONMENTAL INTERACTIONS INFLUENCING THE PRODUCTION OF TYPE 2 DIABETES MELLITUS AND ITS RELATED CONCERNS. EPIGENETIC MODIFICATIONS ASSOCIATED WITH THE ACCEPTANCE OF A SEDENTARY LIFESTYLE AND ENVIRONMENTAL STRESS FACTORS IN RESPONSE TO ENERGY INTAKE AND EXPENDITURE IMBALANCES COMPLEMENT GENETIC ALTERATIONS AND LEAD TO THE PRODUCTION AND ADVANCEMENT OF METABOLIC DISORDERS SUCH AS DIABETES AND OBESITY. METHYLATION OF DNA, HISTONE MODIFICATIONS, AND INCREASES IN THE EXPRESSION OF NON-CODING RNAS CAN RESULT IN REDUCED TRANSCRIPTIONAL ACTIVITY OF KEY BETA-CELL GENES THUS CREATING INSULIN RESISTANCE. EPIGENETICS CONTRIBUTE TO CHANGES IN THE EXPRESSION OF THE UNDERLYING INSULIN RESISTANCE AND INSUFFICIENCY GENE NETWORKS, ALONG WITH LOW-GRADE OBESITY-RELATED INFLAMMATION, INCREASED ROS GENERATION, AND DNA DAMAGE IN MULTIORGANS. THIS REVIEW FOCUSED ON EPIGENETIC MECHANISMS AND METABOLIC REGULATIONS ASSOCIATED WITH HIGH-FAT DIET (HFD)-INDUCED DIABETES MELLITUS. 2022 19 2801 27 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 20 1098 26 COLLATERAL DAMAGE: MATERNAL OBESITY DURING PREGNANCY CONTINUES TO RISE. IMPORTANCE: THE PANDEMIC OF OBESITY DURING PREGNANCY NOW AFFLICTS 1 OUT OF EVERY 2 PREGNANT WOMEN IN THE UNITED STATES. EVEN THOUGH UNINTENDED PREGNANCY HAS DECREASED TO 45% OF ALL PREGNANCIES, 50% OF THOSE UNINTENDED PREGNANCIES OCCUR IN OBESE WOMEN. OBJECTIVE: THIS STUDY AIMS TO IDENTIFY WHY CURRENT LIFESTYLE INTERVENTIONS FOR OBESE PREGNANCY ARE NOT EFFECTIVE AND WHAT THE NEWER COMPLICATIONS ARE FOR OBESITY DURING PREGNANCY. EVIDENCE ACQUISITION: AVAILABLE LITERATURES ON CURRENT TREATMENTS FOR MATERNAL OBESITY WERE REVIEWED FOR EFFECTIVENESS. EMERGING MATERNAL AND INFANT COMPLICATIONS FROM OBESITY DURING PREGNANCY WERE EXAMINED FOR SIGNIFICANCE. RESULTS: LIMITATIONS IN SUCCESSFUL INTERVENTIONS FELL INTO 3 BASIC CATEGORIES TO INCLUDE THE FOLLOWING: (1) PRECONCEPTION WEIGHT LOSS; (2) BARIATRIC SURGERY BEFORE PREGNANCY; AND (3) PREVENTION OF EXCESSIVE GESTATIONAL WEIGHT GAIN DURING PREGNANCY. EMERGING SIGNIFICANT PHYSIOLOGICAL CHANGES FROM MATERNAL OBESITY IS COMPOSED OF INFLAMMATION (PLACENTA AND HUMAN MILK), METABOLISM (HORMONES, MICROBIOME, FATTY ACIDS), AND OFFSPRING OUTCOMES (BODY COMPOSITION, CONGENITAL MALFORMATIONS, CHRONIC KIDNEY DISEASE, ASTHMA, NEURODEVELOPMENT, AND BEHAVIOR). CONCLUSIONS AND RELEVANCE: ARE CURRENT PREPREGNANCY LIFESTYLE AND BEHAVIORAL INTERVENTIONS FEASIBLE TO PREVENT MATERNAL OBESITY COMPLICATIONS? EPIGENETIC AND METABOLOMIC RESEARCH WILL BE CRITICAL TO DETERMINE WHAT IS NEEDED TO BLUNT THE EFFECTS OF MATERNAL OBESITY AND TO DISCOVER SUCCESSFUL TREATMENT. 2020