1 4711 137 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 2 2699 42 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 3 5079 45 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 4 5654 45 SEX, NUTRITION, AND NAFLD: RELEVANCE OF ENVIRONMENTAL POLLUTION. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS THE MOST COMMON FORM OF CHRONIC LIVER DISEASE AND REPRESENTS AN INCREASING PUBLIC HEALTH ISSUE GIVEN THE LIMITED TREATMENT OPTIONS AND ITS ASSOCIATION WITH SEVERAL OTHER METABOLIC AND INFLAMMATORY DISORDERS. THE EPIDEMIC, STILL GROWING PREVALENCE OF NAFLD WORLDWIDE CANNOT BE MERELY EXPLAINED BY CHANGES IN DIET AND LIFESTYLE THAT OCCURRED IN THE LAST FEW DECADES, NOR FROM THEIR ASSOCIATION WITH GENETIC AND EPIGENETIC RISK FACTORS. IT IS CONCEIVABLE THAT ENVIRONMENTAL POLLUTANTS, WHICH ACT AS ENDOCRINE AND METABOLIC DISRUPTORS, MAY CONTRIBUTE TO THE SPREADING OF THIS PATHOLOGY DUE TO THEIR ABILITY TO ENTER THE FOOD CHAIN AND BE INGESTED THROUGH CONTAMINATED FOOD AND WATER. GIVEN THE STRICT INTERPLAY BETWEEN NUTRIENTS AND THE REGULATION OF HEPATIC METABOLISM AND REPRODUCTIVE FUNCTIONS IN FEMALES, POLLUTANT-INDUCED METABOLIC DYSFUNCTIONS MAY BE OF PARTICULAR RELEVANCE FOR THE FEMALE LIVER, DAMPENING SEX DIFFERENCES IN NAFLD PREVALENCE. DIETARY INTAKE OF ENVIRONMENTAL POLLUTANTS CAN BE PARTICULARLY DETRIMENTAL DURING GESTATION, WHEN ENDOCRINE-DISRUPTING CHEMICALS MAY INTERFERE WITH THE PROGRAMMING OF LIVER METABOLISM, ACCOUNTING FOR THE DEVELOPMENTAL ORIGIN OF NAFLD IN OFFSPRING. THIS REVIEW SUMMARIZES CAUSE-EFFECT EVIDENCE BETWEEN ENVIRONMENTAL POLLUTANTS AND INCREASED INCIDENCE OF NAFLD AND EMPHASIZES THE NEED FOR FURTHER STUDIES IN THIS FIELD. 2023 5 4188 48 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 6 4314 38 MICRORNAS AS CONTROLLED SYSTEMS AND CONTROLLERS IN NON-ALCOHOLIC FATTY LIVER DISEASE. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A MULTI-FACETED CONDITION INCLUDING SIMPLE STEATOSIS ALONE OR ASSOCIATED WITH INFLAMMATION AND BALLOONING (NON-ALCOHOLIC STEATOHEPATITIS) AND EVENTUALLY FIBROSIS. THE NAFLD INCIDENCE HAS INCREASED OVER THE LAST TWENTY YEARS BECOMING THE MOST FREQUENT CHRONIC LIVER DISEASE IN INDUSTRIALIZED COUNTRIES. OBESITY, VISCERAL ADIPOSITY, INSULIN RESISTANCE, AND MANY OTHER DISORDERS THAT CHARACTERIZE METABOLIC SYNDROME ARE THE MAJOR PREDISPOSING RISK FACTORS FOR NAFLD. FURTHERMORE, DIFFERENT FACTORS, INCLUDING GENETIC BACKGROUND, EPIGENETIC MECHANISMS AND ENVIRONMENTAL FACTORS, SUCH AS DIET AND PHYSICAL EXERCISE, CONTRIBUTE TO NAFLD DEVELOPMENT AND PROGRESSION. SEVERAL LINES OF EVIDENCE DEMONSTRATE THAT SPECIFIC MICRORNAS EXPRESSION PROFILES ARE STRONGLY ASSOCIATED WITH SEVERAL PATHOLOGICAL CONDITIONS INCLUDING NAFLD. IN NAFLD, MICRORNA DEREGULATION IN RESPONSE TO INTRINSIC GENETIC OR EPIGENETIC FACTORS OR ENVIRONMENTAL FACTORS CONTRIBUTES TO METABOLIC DYSFUNCTION. IN THIS REVIEW WE FOCUSED ON MICRORNAS ROLE BOTH AS CONTROLLED AND CONTROLLERS MOLECULES IN NAFLD DEVELOPMENT AND/OR THEIR EVENTUAL VALUE AS NON-INVASIVE BIOMARKERS OF DISEASE. 2014 7 4710 31 NON-ALCOHOLIC FATTY LIVER DISEASE AND THE IMPACT OF GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS IN THE OFFSPRING. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS THE MOST COMMON CHRONIC LIVER DISEASE WORLDWIDE AND IS STRONGLY ASSOCIATED WITH METABOLIC DEREGULATION. MORE RECENTLY, A SIGNIFICANT IMPACT OF PARENTAL NAFLD IN THE OFFSPRING WAS DEMONSTRATED AND HAS BEEN WIDELY DISCUSSED. HOWEVER, PATHOGENETIC PATHWAYS IMPLICATED IN THE INHERITANCE BY THE OFFSPRING AND RELATIVES ARE STILL UNDER DEBATE. PROBABLY, MULTIPLE MECHANISMS ARE INVOLVED AS WELL AS IN NAFLD PATHOGENESIS ITSELF. AMONG THE MULTIFACTORIAL INVOLVED MECHANISMS, GENETIC, EPIGENETIC AND ENVIRONMENTAL BACKGROUNDS ARE STRONGLY RELATED TO NAFLD DEVELOPMENT IN THE OFFSPRING. THUS, BASED ON RECENT EVIDENCE FROM THE AVAILABLE LITERATURE CONCERNING GENETIC, EPIGENETIC AND ENVIRONMENTAL DISEASE MODIFIERS, THIS REVIEW AIMED TO DISCUSS THE RELATIONSHIP BETWEEN PARENTAL NAFLD AND ITS IMPACT ON THE OFFSPRING. 2022 8 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 9 4779 38 NUTRIENTS, GENETIC FACTORS, AND THEIR INTERACTION IN NON-ALCOHOLIC FATTY LIVER DISEASE AND CARDIOVASCULAR DISEASE. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS THE MOST COMMON CHRONIC LIVER DISEASE IN WESTERN COUNTRIES AND EXPOSE PATIENTS TO INCREASED RISK OF HEPATIC AND CARDIOVASCULAR (CV) MORBIDITY AND MORTALITY. BOTH ENVIRONMENTAL FACTORS AND GENETIC PREDISPOSITION CONTRIBUTE TO THE RISK. AN INAPPROPRIATE DIET, RICH IN REFINED CARBOHYDRATES, ESPECIALLY FRUCTOSE, AND SATURATED FATS, AND POOR IN FIBERS, POLYUNSATURATED FATS, AND VITAMINS IS ONE OF THE MAIN KEY FACTORS, AS WELL AS THE POLYMORPHISM OF PATATIN-LIKE PHOSPHOLIPASE DOMAIN CONTAINING 3 (PNPLA3 GENE) FOR NAFLD AND THE APOLIPOPROTEINS AND THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) FAMILY FOR THE CARDIOVASCULAR DAMAGE. BEYOND GENETIC INFLUENCE, ALSO EPIGENETICS MODIFICATIONS ARE RESPONSIBLE FOR VARIOUS CLINICAL MANIFESTATIONS OF BOTH HEPATIC AND CV DISEASE. INTERESTINGLY, DATA ARE ACCUMULATING ON THE INTERPLAY BETWEEN DIET AND GENETIC AND EPIGENETIC MODIFICATIONS, MODULATING PATHOGENETIC PATHWAYS IN NAFLD AND CV DISEASE. WE REPORT THE MAIN EVIDENCE FROM LITERATURE ON THE INFLUENCE OF BOTH MACRO AND MICRONUTRIENTS IN NAFLD AND CV DAMAGE AND THE ROLE OF GENETICS EITHER ALONE OR COMBINED WITH DIET IN INCREASING THE RISK OF DEVELOPING BOTH DISEASES. UNDERSTANDING THE INTERACTION BETWEEN METABOLIC ALTERATIONS, GENETICS AND DIET ARE ESSENTIAL TO TREAT THE DISEASES AND TAILORING NUTRITIONAL THERAPY TO CONTROL NAFLD AND CV RISK. 2020 10 74 46 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 11 4991 38 PEDIATRIC NON-ALCOHOLIC FATTY LIVER DISEASE: NUTRITIONAL ORIGINS AND POTENTIAL MOLECULAR MECHANISMS. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS THE NUMBER ONE CHRONIC LIVER DISEASE WORLDWIDE AND IS ESTIMATED TO AFFECT NEARLY 40% OF OBESE YOUTH AND UP TO 10% OF THE GENERAL PEDIATRIC POPULATION WITHOUT ANY OBVIOUS SIGNS OR SYMPTOMS. ALTHOUGH THE EARLY STAGES OF NAFLD ARE REVERSIBLE WITH DIET AND LIFESTYLE MODIFICATIONS, DETECTING SUCH STAGES IS HINDERED BY A LACK OF NON-INVASIVE METHODS OF RISK ASSESSMENT AND DIAGNOSIS. THIS ABSENCE OF NON-INVASIVE MEANS OF DIAGNOSIS IS DIRECTLY RELATED TO THE SCARCITY OF LONG-TERM PROSPECTIVE STUDIES OF PEDIATRIC NAFLD IN CHILDREN AND ADOLESCENTS. IN THE MAJORITY OF PEDIATRIC NAFLD CASES, THE MECHANISMS DRIVING THE ORIGIN AND RAPID PROGRESSION OF NAFLD REMAIN UNKNOWN. THE PROGRESSION FROM NAFLD TO NON-ALCOHOLIC STEATOHEPATITIS (NASH) IN YOUTH IS ASSOCIATED WITH UNIQUE HISTOLOGICAL FEATURES AND POSSIBLE IMMUNE PROCESSES AND METABOLIC PATHWAYS THAT MAY REFLECT DIFFERENT MECHANISMS COMPARED WITH ADULTS. RECENT DATA SUGGEST THAT CIRCULATING MICRORNAS (MIRNAS) ARE IMPORTANT NEW BIOMARKERS UNDERLYING PATHWAYS OF LIVER INJURY. SEVERAL FACTORS MAY CONTRIBUTE TO PEDIATRIC NAFLD DEVELOPMENT, INCLUDING HIGH-SUGAR DIETS, IN UTERO EXPOSURES VIA EPIGENETIC ALTERATIONS, CHANGES IN THE NEONATAL MICROBIOME, AND ALTERED IMMUNE SYSTEM DEVELOPMENT AND MITOCHONDRIAL FUNCTION. THIS REVIEW FOCUSES ON THE UNIQUE ASPECTS OF PEDIATRIC NAFLD AND HOW NUTRITIONAL EXPOSURES IMPACT THE IMMUNE SYSTEM, MITOCHONDRIA, AND LIVER/GASTROINTESTINAL METABOLIC HEALTH. THESE FACTORS HIGHLIGHT THE NEED FOR ANSWERS TO HOW NAFLD DEVELOPS IN CHILDREN AND FOR EARLY STAGE-SPECIFIC INTERVENTIONS. 2020 12 4586 39 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 13 6264 42 THE MULTIPLE-HIT PATHOGENESIS OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD). NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS INCREASINGLY PREVALENT AND REPRESENTS A GROWING CHALLENGE IN TERMS OF PREVENTION AND TREATMENT. DESPITE ITS HIGH PREVALENCE, ONLY A SMALL MINORITY OF AFFECTED PATIENTS DEVELOPS INFLAMMATION AND SUBSEQUENTLY FIBROSIS AND CHRONIC LIVER DISEASE, WHILE MOST OF THEM ONLY EXHIBIT SIMPLE STEATOSIS. IN THIS CONTEXT, THE FULL UNDERSTANDING OF THE MECHANISMS UNDERLYING THE DEVELOPMENT OF NAFLD AND NON-ALCOHOLIC STEATOHEPATITIS (NASH) IS OF EXTREME IMPORTANCE; DESPITE ADVANCES IN THIS FIELD, KNOWLEDGE ON THE PATHOGENESIS OF NAFLD IS STILL INCOMPLETE. THE 'TWO-HIT' HYPOTHESIS IS NOW OBSOLETE, AS IT IS INADEQUATE TO EXPLAIN THE SEVERAL MOLECULAR AND METABOLIC CHANGES THAT TAKE PLACE IN NAFLD. THE "MULTIPLE HIT" HYPOTHESIS CONSIDERS MULTIPLE INSULTS ACTING TOGETHER ON GENETICALLY PREDISPOSED SUBJECTS TO INDUCE NAFLD AND PROVIDES A MORE ACCURATE EXPLANATION OF NAFLD PATHOGENESIS. SUCH HITS INCLUDE INSULIN RESISTANCE, HORMONES SECRETED FROM THE ADIPOSE TISSUE, NUTRITIONAL FACTORS, GUT MICROBIOTA AND GENETIC AND EPIGENETIC FACTORS. IN THIS ARTICLE, WE REVIEW THE FACTORS THAT FORM THIS HYPOTHESIS. 2016 14 3293 44 HIGH FAT DIET-TRIGGERED NON-ALCOHOLIC FATTY LIVER DISEASE: A REVIEW OF PROPOSED MECHANISMS. OBESITY IS CHARACTERIZED BY THE DEPOSITION OF EXCESSIVE BODY FAT, AND IS CAUSED BY ENERGY IMBALANCE, ESPECIALLY WHEN CONSUMING FAT-RICH DIETS. HIGH FAT DIET (HFD)-ASSOCIATED OBESITY IS GREATLY COMMON IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) THAT IS EMERGING AS ONE OF THE MOST UNIVERSAL CAUSES OF LIVER DISEASE WORLDWIDE, ESPECIALLY IN WESTERN COUNTRIES. IN SPITE OF ITS HIGH PREVALENCE, ONLY A SMALL PROPORTION OF AFFECTED INDIVIDUALS WILL BECOME INFLAMED, FOLLOWED BY FIBROSIS AND CHRONIC LIVER DISEASES, AND MOST PATIENTS ONLY SHOW SIMPLE STEATOSIS. IN THIS CASE, THE FULL COMPREHENSION OF THE MECHANISMS UNDERLYING THE PROGRESSION OF NAFLD IS OF EXTREME SIGNIFICANCE; IN SPITE OF PROGRESS IN THIS FIELD, AWARENESS ON THE DEVELOPMENT OF NAFLD IS STILL INCOMPLETE. TRADITIONALLY, LIVER STEATOSIS IS COMMONLY CONNECTED WITH HFD, OBESITY, AND INSULIN RESISTANCE (IR). RECENTLY, VARIOUS POSSIBLE MECHANISMS HAVE BEEN PUT FORWARD FOR LIVER DAMAGE, INCLUDING ENDOPLASMIC RETICULUM STRESS, PERTURBATION OF AUTOPHAGY, MITOCHONDRIAL DYSFUNCTION, HEPATOCELLULAR APOPTOSIS, GUT MICROBIOTA IMBALANCE, DYSREGULATION OF MICRORNAS, AND GENETIC/EPIGENETIC RISK FACTORS, AS WELL AS AN INCREASE IN INFLAMMATORY RESPONSES, AMONG MANY OTHERS. COLLECTIVELY, THESE PROPOSED MECHANISMS ALLOW FOR A VARIETY OF HITS ACTING TOGETHER ON SUBJECTS TO MEDIATED NAFLD AND WILL OFFER A MORE ACCURATE EXPLANATION FOR PROGRESSION OF NAFLD. THEREFORE, THIS REVIEW SUMMARIZES THE PRESENT INFORMATION CONCERNING NAFLD AFTER HFD EXPOSURE, AS WELL AS DISCUSSES POSSIBLE MECHANISMS THROUGH WHICH IT MAY ARISE. 2020 15 5558 40 ROLE OF GUT MICROBIOTA IN THE AETIOLOGY OF OBESITY: PROPOSED MECHANISMS AND REVIEW OF THE LITERATURE. THE AETIOLOGY OF OBESITY HAS BEEN ATTRIBUTED TO SEVERAL FACTORS (ENVIRONMENTAL, DIETARY, LIFESTYLE, HOST, AND GENETIC FACTORS); HOWEVER NONE OF THESE FULLY EXPLAIN THE INCREASE IN THE PREVALENCE OF OBESITY WORLDWIDE. GUT MICROBIOTA LOCATED AT THE INTERFACE OF HOST AND ENVIRONMENT IN THE GUT ARE A NEW AREA OF RESEARCH BEING EXPLORED TO EXPLAIN THE EXCESS ACCUMULATION OF ENERGY IN OBESE INDIVIDUALS AND MAY BE A POTENTIAL TARGET FOR THERAPEUTIC MANIPULATION TO REDUCE HOST ENERGY STORAGE. SEVERAL MECHANISMS HAVE BEEN SUGGESTED TO EXPLAIN THE ROLE OF GUT MICROBIOTA IN THE AETIOLOGY OF OBESITY SUCH AS SHORT CHAIN FATTY ACID PRODUCTION, STIMULATION OF HORMONES, CHRONIC LOW-GRADE INFLAMMATION, LIPOPROTEIN AND BILE ACID METABOLISM, AND INCREASED ENDOCANNABINOID RECEPTOR SYSTEM TONE. HOWEVER, EVIDENCE FROM ANIMAL AND HUMAN STUDIES CLEARLY INDICATES CONTROVERSIES IN DETERMINING THE CAUSE OR EFFECT RELATIONSHIP BETWEEN THE GUT MICROBIOTA AND OBESITY. METAGENOMICS BASED STUDIES INDICATE THAT FUNCTIONALITY RATHER THAN THE COMPOSITION OF GUT MICROBIOTA MAY BE IMPORTANT. FURTHER MECHANISTIC STUDIES CONTROLLING FOR ENVIRONMENTAL AND EPIGENETIC FACTORS ARE THEREFORE REQUIRED TO HELP UNRAVEL OBESITY PATHOGENESIS. 2016 16 1412 46 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 17 2862 45 FRUCTOSE-MEDIATED EFFECTS ON GENE EXPRESSION AND EPIGENETIC MECHANISMS ASSOCIATED WITH NAFLD PATHOGENESIS. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A CHRONIC, FREQUENTLY PROGRESSIVE CONDITION THAT DEVELOPS IN RESPONSE TO EXCESSIVE HEPATOCYTE FAT ACCUMULATION (I.E., STEATOSIS) IN THE ABSENCE OF SIGNIFICANT ALCOHOL CONSUMPTION. LIVER STEATOSIS DEVELOPS AS A RESULT OF IMBALANCED LIPID METABOLISM, DRIVEN LARGELY BY INCREASED RATES OF DE NOVO LIPOGENESIS AND HEPATIC FATTY ACID UPTAKE AND REDUCED FATTY ACID OXIDATION AND/OR DISPOSAL TO THE CIRCULATION. FRUCTOSE IS A NATURALLY OCCURRING SIMPLE SUGAR, WHICH IS MOST COMMONLY CONSUMED IN MODERN DIETS IN THE FORM OF SUCROSE, A DISACCHARIDE COMPRISED OF ONE MOLECULE OF FRUCTOSE COVALENTLY BONDED WITH ONE MOLECULE OF GLUCOSE. A NUMBER OF OBSERVATIONAL AND EXPERIMENTAL STUDIES HAVE DEMONSTRATED DETRIMENTAL EFFECTS OF DIETARY FRUCTOSE CONSUMPTION NOT ONLY ON DIVERSE METABOLIC OUTCOMES SUCH AS INSULIN RESISTANCE AND OBESITY, BUT ALSO ON HEPATIC STEATOSIS AND NAFLD-RELATED FIBROSIS. DESPITE THE COMPELLING EVIDENCE THAT EXCESSIVE FRUCTOSE CONSUMPTION IS ASSOCIATED WITH THE PRESENCE OF NAFLD AND MAY EVEN PROMOTE THE DEVELOPMENT AND PROGRESSION OF NAFLD TO MORE CLINICALLY SEVERE PHENOTYPES, THE MOLECULAR MECHANISMS BY WHICH FRUCTOSE ELICITS EFFECTS ON DYSREGULATED LIVER METABOLISM REMAIN UNCLEAR. EMERGING DATA SUGGEST THAT DIETARY FRUCTOSE MAY DIRECTLY ALTER THE EXPRESSION OF GENES INVOLVED IN LIPID METABOLISM, INCLUDING THOSE THAT INCREASE HEPATIC FAT ACCUMULATION OR REDUCE HEPATIC FAT REMOVAL. THE AIM OF THIS REVIEW IS TO SUMMARIZE THE CURRENT RESEARCH SUPPORTING A ROLE FOR DIETARY FRUCTOSE INTAKE IN THE MODULATION OF TRANSCRIPTOMIC AND EPIGENETIC MECHANISMS UNDERLYING THE PATHOGENESIS OF NAFLD. 2020 18 44 38 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 4712 36 NON-ALCOHOLIC FATTY LIVER DISEASE: METABOLIC, GENETIC, EPIGENETIC AND ENVIRONMENTAL RISK FACTORS. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ONE OF THE MOST FREQUENT CAUSES OF CHRONIC LIVER DISEASE IN THE WESTERN WORLD, PROBABLY DUE TO THE GROWING PREVALENCE OF OBESITY, METABOLIC DISEASES, AND EXPOSURE TO SOME ENVIRONMENTAL AGENTS. IN CERTAIN PATIENTS, SIMPLE HEPATIC STEATOSIS CAN PROGRESS TO NON-ALCOHOLIC STEATOHEPATITIS (NASH), WHICH CAN SOMETIMES LEAD TO LIVER CIRRHOSIS AND ITS COMPLICATIONS INCLUDING HEPATOCELLULAR CARCINOMA. UNDERSTANDING THE MECHANISMS THAT CAUSE THE PROGRESSION OF NAFLD TO NASH IS CRUCIAL TO BE ABLE TO CONTROL THE ADVANCEMENT OF THE DISEASE. THE MAIN HYPOTHESIS CONSIDERS THAT IT IS DUE TO MULTIPLE FACTORS THAT ACT TOGETHER ON GENETICALLY PREDISPOSED SUBJECTS TO SUFFER FROM NAFLD INCLUDING INSULIN RESISTANCE, NUTRITIONAL FACTORS, GUT MICROBIOTA, AND GENETIC AND EPIGENETIC FACTORS. IN THIS ARTICLE, WE WILL DISCUSS THE EPIDEMIOLOGY OF NAFLD, AND WE OVERVIEW SEVERAL TOPICS THAT INFLUENCE THE DEVELOPMENT OF THE DISEASE FROM SIMPLE STEATOSIS TO LIVER CIRRHOSIS AND ITS POSSIBLE COMPLICATIONS. 2021 20 4087 34 MATERNAL OBESITY INCREASES THE RISK OF METABOLIC DISEASE AND IMPACTS RENAL HEALTH IN OFFSPRING. OBESITY, TOGETHER WITH INSULIN RESISTANCE, PROMOTES MULTIPLE METABOLIC ABNORMALITIES AND IS STRONGLY ASSOCIATED WITH AN INCREASED RISK OF CHRONIC DISEASE INCLUDING TYPE 2 DIABETES (T2D), HYPERTENSION, CARDIOVASCULAR DISEASE, NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND CHRONIC KIDNEY DISEASE (CKD). THE INCIDENCE OF OBESITY CONTINUES TO RISE IN ASTRONOMICAL PROPORTIONS THROUGHOUT THE WORLD AND AFFECTS ALL THE DIFFERENT STAGES OF THE LIFESPAN. IMPORTANTLY, THE PROPORTION OF WOMEN OF REPRODUCTIVE AGE WHO ARE OVERWEIGHT OR OBESE IS INCREASING AT AN ALARMING RATE AND HAS POTENTIAL RAMIFICATIONS FOR OFFSPRING HEALTH AND DISEASE RISK. EVIDENCE SUGGESTS A STRONG LINK BETWEEN THE INTRAUTERINE ENVIRONMENT AND DISEASE PROGRAMMING. THE CURRENT REVIEW WILL DESCRIBE THE IMPORTANCE OF THE INTRAUTERINE ENVIRONMENT IN THE DEVELOPMENT OF METABOLIC DISEASE, INCLUDING KIDNEY DISEASE. IT WILL DETAIL THE KNOWN MECHANISMS OF FETAL PROGRAMMING, INCLUDING THE ROLE OF EPIGENETIC MODULATION. THE EVIDENCE FOR THE ROLE OF MATERNAL OBESITY IN THE DEVELOPMENTAL PROGRAMMING OF CKD IS DERIVED MOSTLY FROM OUR RODENT MODELS WHICH WILL BE DESCRIBED. THE CLINICAL IMPLICATION OF SUCH FINDINGS WILL ALSO BE DISCUSSED. 2018