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 4796 44 NUTRITIONAL INTERVENTION AS AN ESSENTIAL PART OF MULTIPLE SCLEROSIS TREATMENT? MULTIPLE SCLEROSIS (MS) IS A CHRONIC INFLAMMATORY AND DEMYELINATING DISEASE OF THE CENTRAL NERVOUS SYSTEM. IN ADDITION TO THE GENETIC, EPIGENETIC AND IMMUNOLOGICAL COMPONENTS, VARIOUS OTHER FACTORS, E.G. UNHEALTHY DIETARY HABITS, PLAY A ROLE IN THE MS PATHOGENESIS. DIETARY INTERVENTION IS A HIGHLY APPEALING APPROACH, AS IT PRESENTS A SIMPLE AND RELATIVELY LOW RISK METHOD TO POTENTIALLY IMPROVE OUTCOMES IN PATIENTS WITH BRAIN DISORDERS IN ORDER TO ACHIEVE REMISSION AND IMPROVEMENT OF CLINICAL STATUS, WELL-BEING AND LIFE EXPECTANCY OF PATIENTS WITH MS. THE IMPORTANCE OF SATURATED FAT INTAKE RESTRICTION FOR THE CLINICAL STATUS IMPROVEMENT OF MS PATIENTS WAS POINTED FOR THE FIRST TIME IN 1950S. RECENTLY, DECREASED RISK OF FIRST CLINICAL DIAGNOSIS OF CNS DEMYELINATION ASSOCIATED WITH HIGHER INTAKE OF OMEGA-3 POLYUNSATURATED FATTY ACIDS PARTICULARLY ORIGINATING FROM FISH WAS REPORTED. ONLY FEW CLINICAL TRIALS HAVE BEEN PERFORMED TO ADDRESS THE QUESTION OF THE ROLE OF DIETARY INTERVENTION, SUCH IS E.G. LOW SATURATED FAT DIET IN MS TREATMENT. THIS REVIEW SUMMARIZES CURRENT KNOWLEDGE ABOUT THE EFFECT OF DIFFERENT DIETARY APPROACHES (DIETS LOW IN SATURATED FAT AND DIETARY SUPPLEMENTS SUCH AS FISH OIL, LIPOIC ACID, OMEGA-3 POLYUNSATURATED FATTY ACIDS, SEEDS OILS, HIGH FIBER DIET, VITAMIN D, ETC.) ON NEUROLOGICAL SIGNS, PATIENT'S WELL-BEING, PHYSICAL AND INFLAMMATORY STATUS. SO FAR THE RESULTS ARE NOT CONCLUSIVE, THEREFORE MUCH MORE RESEARCH IS NEEDED TO CONFIRM AND TO UNDERSTAND THE EFFECTIVENESS OF THESE DIETARY INTERVENTIONS IN THE LONG TERM AND WELL DEFINED STUDIES. 2018 3 4977 50 PATHOPHYSIOLOGY AND EVOLUTIONARY ASPECTS OF DIETARY FATS AND LONG-CHAIN POLYUNSATURATED FATTY ACIDS ACROSS THE LIFE CYCLE. DIETARY FAT IS OUR SECOND MOST IMPORTANT ENERGY-PRODUCING MACRONUTRIENT. IT ALSO CONTAINS FATTY ACIDS AND VITAMINS ESSENTIAL FOR GROWTH, DEVELOPMENT, AND MAINTENANCE OF GOOD HEALTH. DIETARY FAT QUANTITY AND QUALITY HAVE BEEN SUBJECT TO TREMENDOUS CHANGE OVER THE PAST 10,000 YEARS. THIS HAS, TOGETHER WITH OTHER MAN-MADE CHANGES IN OUR ENVIRONMENT, CAUSED A CONFLICT WITH OUR SLOWLY ADAPTING GENOME THAT IS IMPLICATED IN "TYPICALLY WESTERN" DISEASES. RATHER THAN REDUCING OUR LIFE EXPECTANCY, THESE DISEASES NOTABLY DIMINISH OUR NUMBER OF YEARS IN HEALTH. IMPORTANT CHANGES IN DIETARY FAT QUALITY ARE THE INCREASED INTAKES OF CERTAIN SATURATED FATTY ACIDS (SAFA) AND LINOLEIC ACID (LA), INTRODUCTION OF INDUSTRIALLY PRODUCED TRANS FATTY ACIDS, AND REDUCED INTAKES OF OMEGA3 FATTY ACIDS, NOTABLY ALPHA-LINOLENIC ACID (ALA) FROM VEGETABLE SOURCES AND EICOSAPENTAENOIC ACID (EPA) AND DOCOSAHEXAENOIC ACID (DHA) FROM FISH. THE PATHOPHYSIOLOGICAL EFFECTS OF THESE CHANGES ARE DIVERSE, BUT ARE INCREASINGLY ASCRIBED TO INDUCTION OF A PROINFLAMMATORY STATE THAT PROGRESSES EASILY TO CHRONIC LOW-GRADE INFLAMMATION. THE LATTER MIGHT AFFECT VIRTUALLY ALL ORGANS AND SYSTEMS, POSSIBLY BEGINNING AT CONCEPTION, AND POSSIBLY EVEN PRIOR TO GAMETOGENESIS THROUGH EPIGENETIC ALTERATIONS. LOW-GRADE INFLAMMATION MIGHT BE A COMMON DENOMINATOR OF THE METABOLIC SYNDROME AND ITS SEQUELAE (E.G., CORONARY ARTERY DISEASE (CAD), DIABETES MELLITUS TYPE 2, SOME TYPES OF CANCER, AND PREGNANCY COMPLICATIONS), SOME PSYCHIATRIC DISEASES (E.G., MAJOR AND POSTPARTUM DEPRESSION, SCHIZOPHRENIA, AND AUTISM), AND NEURODEGENERATIVE DISEASES (E.G., ALZHEIMER'S DISEASE, PARKINSON'S DISEASE). THE LONG-CHAIN POLYUNSATURATED FATTY ACIDS (LCPUFA) ARACHIDONIC ACID (AA), EPA, AND DHA ARE INTIMATELY RELATED TO THE INITIATION AND RESOLUTION OF INFLAMMATORY RESPONSES. THE CURRENT BALANCE BETWEEN AA AND EPA + DHA IS HOWEVER DISTURBED BY THE DOMINANCE OF AA, WHICH ORIGINATES FROM THE DIET OR SYNTHESIS FROM LA. LCPUFA ARE TOGETHER WITH THEIR HIGHLY POTENT METABOLITES (PROSTAGLANDINS, THROMBOXANES, LEUKOTRIENES, RESOLVINS, AND (NEURO)PROTECTINS) INVOLVED IN THE FUNCTIONING OF MEMBRANE-BOUND RECEPTORS, TRANSPORTERS, ION CHANNELS, AND ENZYMES, AND ALSO IN SIGNAL TRANSDUCTION AND GENE EXPRESSION. AMONG THEIR MANY TARGETS ARE NUCLEAR RECEPTORS WHICH, UPON LIGATION WITH LCPUFA AND THEIR METABOLITES, FUNCTION AS TRANSCRIPTION FACTORS OF A VARIETY OF GENES FUNCTIONING IN MANY PATHWAYS. FOR INSTANCE, THE TARGETED PEROXISOME PROLIFERATORS-ACTIVATED RECEPTORS (PPARS) ARE STRATEGIC INTERMEDIATES IN THE COORDINATED EXPRESSION OF PROTEINS WITH FUNCTIONS IN, FOR EXAMPLE, LIPID AND GLUCOSE HOMEOSTASIS AND INFLAMMATORY REACTIONS. MANY INTERVENTIONS HAVE BEEN CONDUCTED WITH LCPUFA, ESPECIALLY EPA AND DHA, AIMING AT PRIMARY AND SECONDARY CAD PREVENTIONS, IMPROVEMENT OF FETAL AND NEWBORN (BRAIN) DEVELOPMENT BY SUPPLEMENTATION DURING PREGNANCY OR EARLY POSTNATAL LIFE, AND IN PSYCHIATRIC DISEASES. CONSENSUS HAS BEEN REACHED THAT THOSE IN CAD AND DEPRESSION ARE POSITIVE, ALTHOUGH MORE LARGE-SCALE TRIALS ARE NEEDED. MANY RECOMMENDATIONS FOR THE INTAKES OF SATURATED FAT, TRANS FAT AND EPA + DHA HAVE BEEN ISSUED, NOTABLY FOR CAD PREVENTION, AND ALSO FOR EPA + DHA INTAKES BY PREGNANT WOMEN AND FOR AA, EPA, AND DHA INTAKES BY NEWBORNS. THE ULTIMATE GOAL MIGHT, HOWEVER, BE TO RETURN TO THE FAT QUALITY OF OUR ANCIENT DIET ON WHICH OUR GENES HAVE EVOLVED DURING THE PAST MILLION YEARS OF EVOLUTION, WHILE THIS ACTUALLY APPLIES FOR OUR ENTIRE DIETARY COMPOSITION AND LIFESTYLE, AS TRANSLATED TO THE CULTURE OF THE CURRENT SOCIETY. 2010 4 2794 31 FATTY ACIDS, EPIGENETIC MECHANISMS AND CHRONIC DISEASES: A SYSTEMATIC REVIEW. BACKGROUND: CHRONIC ILLNESSES LIKE OBESITY, TYPE 2 DIABETES (T2D) AND CARDIOVASCULAR DISEASES, ARE WORLDWIDE MAJOR CAUSES OF MORBIDITY AND MORTALITY. THESE PATHOLOGICAL CONDITIONS INVOLVE INTERACTIONS BETWEEN ENVIRONMENTAL, GENETIC, AND EPIGENETIC FACTORS. RECENT ADVANCES IN NUTRIEPIGENOMICS ARE CONTRIBUTING TO CLARIFY THE ROLE OF SOME NUTRITIONAL FACTORS, INCLUDING DIETARY FATTY ACIDS IN GENE EXPRESSION REGULATION. THIS SYSTEMATIC REVIEW ASSESSES CURRENTLY AVAILABLE INFORMATION CONCERNING THE ROLE OF THE DIFFERENT FATTY ACIDS ON EPIGENETIC MECHANISMS THAT AFFECT THE DEVELOPMENT OF CHRONIC DISEASES OR INDUCE PROTECTIVE EFFECTS ON METABOLIC ALTERATIONS. METHODS: A TARGETED SEARCH WAS CONDUCTED IN THE PUBMED/MEDLINE DATABASES USING THE KEYWORDS "FATTY ACIDS AND EPIGENETIC". THE DATA WERE ANALYZED ACCORDING TO THE PRISMA-P GUIDELINES. RESULTS: CONSUMPTION FATTY ACIDS LIKE N-3 PUFA: EPA AND DHA, AND MUFA: OLEIC AND PALMITOLEIC ACID WAS ASSOCIATED WITH AN IMPROVEMENT OF METABOLIC ALTERATIONS. ON THE OTHER HAND, FATTY ACIDS THAT HAVE BEEN ASSOCIATED WITH THE PRESENCE OR DEVELOPMENT OF OBESITY, T2D, PRO-INFLAMMATORY PROFILE, ATHEROSCLEROSIS AND IR WERE N-6 PUFA, SATURATED FATTY ACIDS (STEARIC AND PALMITIC), AND TRANS FATTY ACIDS (ELAIDIC), HAVE BEEN ALSO LINKED WITH EPIGENETIC CHANGES. CONCLUSIONS: FATTY ACIDS CAN REGULATE GENE EXPRESSION BY MODIFYING EPIGENETIC MECHANISMS AND CONSEQUENTLY RESULT IN POSITIVE OR NEGATIVE IMPACTS ON METABOLIC OUTCOMES. 2019 5 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 6 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 7 751 30 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 8 1373 34 DEVELOPMENTAL ORIGINS OF NONALCOHOLIC FATTY LIVER DISEASE. OBESE PREGNANT WOMEN MAY TRANSMIT THEIR METABOLIC PHENOTYPE TO OFFSPRING, LEADING TO A CYCLE OF OBESITY AND DIABETES OVER GENERATIONS. EARLY CHILDHOOD OBESITY PREDICTS NONALCOHOLIC FATTY LIVER DISEASE (NAFLD), THE MOST COMMON CHRONIC HUMAN LIVER DISEASE. THE FETUS MAY BE VULNERABLE TO STEATOSIS BECAUSE IMMATURE FETAL ADIPOSE DEPOTS ARE NOT AVAILABLE TO BUFFER THE EXCESS TRANSPLACENTAL LIPID DELIVERY IN MATERNAL OBESITY. IN ANIMAL MODELS, IN UTERO HIGH-FAT DIET EXPOSURE RESULTS IN AN INCREASE IN THE ACCUMULATION OF LIVER TRIGLYCERIDES IN OFFSPRING AND INCREASED HEPATIC OXIDATIVE STRESS AND APOPTOSIS, PERHAPS PRIMING THE LIVER FOR LATER DEVELOPMENT OF NAFLD. INNATE IMMUNE DYSFUNCTION AND NECROINFLAMMATORY CHANGES HAVE BEEN OBSERVED IN POSTNATAL OFFSPRING LIVER OF ANIMALS BORN TO HIGH-FAT-FED DAMS. POSTWEANING, LIVERS OF OFFSPRING EXPOSED TO MATERNAL HIGH-FAT FEEDING IN UTERO SHARE PATHOPHYSIOLOGIC FEATURES WITH HUMAN NAFLD, INCLUDING INCREASED DE NOVO LIPOGENESIS AND DECREASED FREE FATTY ACID OXIDATION. HUMAN STUDIES USING MAGNETIC RESONANCE IMAGING HAVE SHOWN THAT MATERNAL BMI PREDICTS INFANT INTRAHEPATOCELLULAR LIPID STORAGE, AS SEEN IN ANIMAL MODELS. THE GENERATIONAL TRANSFER OF NAFLD MAY OCCUR VIA EPIGENETIC CHANGES IN OFFSPRING LIVER. TRANSMISSION OF MICROBIOTA FROM MOTHER TO INFANT MAY IMPACT ENERGY RETENTION AND IMMUNE FUNCTION THAT CONTRIBUTE TO A PREDISPOSITION TO NAFLD. 2014 9 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 10 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 11 5010 34 PEROXIDATION OF LINOLEIC, ARACHIDONIC AND OLEIC ACID IN RELATION TO THE INDUCTION OF OXIDATIVE DNA DAMAGE AND CYTOGENETIC EFFECTS. IN THE PRESENT STUDY, THE POSSIBLE ROLE OF THE POLYUNSATURATED FATTY ACIDS LINOLEIC AND ARACHIDONIC ACID IN THE CHEMICAL INDUCTION OF CARCINOGENESIS HAS BEEN INVESTIGATED. ANALYSIS OF 7,8-DIHYDRO-8-OXO-2'-DEOXYGUANOSINE (8-OXODG) LEVELS IN 2'-DEOXYGUANOSINE (DG) AND ISOLATED DNA HAS DEMONSTRATED THAT LINOLEIC AND ARACHIDONIC ACID ARE CAPABLE OF INDUCING THIS SPECIFIC GENOTOXIC DAMAGE. THIS EFFECT APPEARS TO BE RELATED TO THE DEGREE OF FATTY ACID UNSATURATION, SINCE IT WAS NOT INDUCED BY MONOUNSATURATED OLEIC ACID. ENZYMATIC PEROXIDATION OF LINOLEIC AND ARACHIDONIC ACID RESULTED IN A SIGNIFICANT INCREASE IN OXIDATIVE DNA DAMAGE. STUDIES ON THE INTERFERENCE OF RADICAL SCAVENGERS WITH THE INDUCTION OF 8-OXODG IN COMBINATION WITH ELECTRON SPIN RESONANCE SPECTROSCOPY DEMONSTRATED THAT THE SUPEROXIDE ANION WAS GENERATED DURING PEROXIDATION OF THESE FATTY ACIDS AND THAT SINGLET OXYGEN IS MOST LIKELY INVOLVED IN THE FORMATION OF OXIDATIVE DNA DAMAGE. THE LEVEL OF OXIDATIVE DAMAGE IN DG AND SINGLE-STRANDED DNA WAS HIGHER AS COMPARED TO THAT IN NATIVE DNA AFTER EQUIMOLAR TREATMENT. EXPOSURE OF HUMAN LYMPHOCYTES TO LINOLEIC OR ARACHIDONIC ACID DID NOT RESULT IN A SIGNIFICANT INCREASE IN LEVELS OF 8-OXODG. THIS MAY INDICATE THAT THE RATE OF INTRACELLULAR PEROXIDATION IS RELATIVELY LOW AND/OR THAT NUCLEAR DNA IN INTACT CELLS IS EFFECTIVELY PROTECTED AGAINST GENETIC DAMAGE INDUCED BY REACTIVE OXYGEN SPECIES. IT IS THEREFORE CONCLUDED THAT RELATIVELY SHORT PERIODS OF LINOLEIC OR ARACHIDONIC ACID ADMINISTRATION ARE NOT LIKELY TO IMPOSE A DIRECT GENOTOXIC RISK. IT CAN, HOWEVER, NOT BE EXCLUDED THAT CHRONIC EXPOSURE TO POLYUNSATURATED FATTY ACIDS INDUCES OXIDATIVE DNA DAMAGE OR IS RELATED TO CANCER RISK BY EPIGENETIC MECHANISMS, AS IS ALSO INDICATED BY THE OBSERVED CYTOTOXIC EFFECTS OF LINOLEIC AND ARACHIDONIC ACID. 1994 12 2835 43 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 13 2320 39 EPIGENETIC REGULATION OF GENE EXPRESSION AND M2 MACROPHAGE POLARIZATION AS NEW POTENTIAL OMEGA-3 POLYUNSATURATED FATTY ACID TARGETS IN COLON INFLAMMATION AND CANCER. INTRODUCTION: IT HAS BECOME INCREASINGLY CLEAR THAT DIETARY HABITS MAY AFFECT THE RISK/PROGRESSION OF CHRONIC DISEASES WITH A PATHOGENIC INFLAMMATORY COMPONENT, SUCH AS COLORECTAL CANCER. CONSIDERABLE ATTENTION HAS BEEN DIRECTED TOWARD THE ABILITY OF NUTRITIONAL AGENTS TO TARGET KEY MOLECULAR PATHWAYS INVOLVED IN THESE INFLAMMATORY-RELATED DISEASES. AREAS COVERED: OMEGA-3 POLYUNSATURATED FATTY ACIDS (PUFA) AND THEIR OXIDATIVE METABOLITES HAVE ATTRACTED CONSIDERABLE INTEREST AS POSSIBLE ANTI-INFLAMMATORY AND ANTI-CANCER AGENTS, ESPECIALLY IN AREAS SUCH AS THE LARGE BOWEL, WHERE THE INFLUENCE OF ORALLY INTRODUCED SUBSTANCES IS HIGH AND TUMORS SHOW DERANGED PUFA PATTERNS. ON THIS BASIS, WE HAVE ANALYZED PRE-CLINICAL FINDINGS THAT HAVE RECENTLY REVEALED NEW INSIGHT INTO THE MOLECULAR PATHWAYS TARGETED BY OMEGA-3 PUFA. EXPERT OPINION: THE FINDINGS ANALYZED HEREIN DEMONSTRATE THAT OMEGA-3 PUFA MAY EXERT BENEFICIAL EFFECTS BY TARGETING THE EPIGENETIC REGULATION OF GENE EXPRESSION AND ALTERING M2 MACROPHAGE POLARIZATION DURING THE INFLAMMATORY RESPONSE. THESE MECHANISMS NEED TO BE BETTER EXPLORED IN THE LARGE BOWEL, AND FURTHER STUDIES COULD BETTER CLARIFY THEIR ROLE AND THE POTENTIAL OF DIETARY INTERVENTIONS WITH OMEGA-3 PUFA IN THE LARGE BOWEL. THE EPIGENOMIC MECHANISM IS DISCUSSED IN VIEW OF THE POTENTIAL OF OMEGA-3 PUFA TO ENHANCE THE EFFICACY OF OTHER AGENTS USED IN THE THERAPY OF COLORECTAL CANCER. 2016 14 6441 36 THERAPEUTIC APPROACHES FOR NONALCOHOLIC FATTY LIVER DISEASE: ESTABLISHED TARGETS AND DRUGS. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD), AS A MULTISYSTEMIC DISEASE, IS THE MOST PREVALENT CHRONIC LIVER DISEASE CHARACTERIZED BY EXTREMELY COMPLEX PATHOGENIC MECHANISMS AND MULTIFACTORIAL ETIOLOGY, WHICH OFTEN DEVELOPS AS A CONSEQUENCE OF OBESITY, METABOLIC SYNDROME. PATHOPHYSIOLOGICAL MECHANISMS INVOLVED IN THE DEVELOPMENT OF NAFLD INCLUDE DIET, OBESITY, INSULIN RESISTANCE (IR), GENETIC AND EPIGENETIC DETERMINANTS, INTESTINAL DYSBIOSIS, OXIDATIVE/NITROSATIVE STRESS, AUTOPHAGY DYSREGULATION, HEPATIC INFLAMMATION, GUT-LIVER AXIS, GUT MICROBES, IMPAIRED MITOCHONDRIAL METABOLISM AND REGULATION OF HEPATIC LIPID METABOLISM. SOME OF THE NEW DRUGS FOR THE TREATMENT OF NAFLD ARE INTRODUCED HERE. ALL OF THEM ACHIEVE THERAPEUTIC OBJECTIVES BY INTERFERING WITH CERTAIN PATHOPHYSIOLOGICAL PATHWAYS OF NAFLD, INCLUDING FIBROBLAST GROWTH FACTORS (FGF) ANALOGUES, PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPARS) AGONISTS, GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AGONISTS, G PROTEIN-COUPLED RECEPTORS (GPCRS), SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS (SGLT-2I), FARNESOID X RECEPTOR (FXR), FATTY ACID SYNTHASE INHIBITOR (FASNI), ANTIOXIDANTS, ETC. THIS REVIEW DESCRIBES SOME PATHOPHYSIOLOGICAL MECHANISMS OF NAFLD AND ESTABLISHED TARGETS AND DRUGS. 2023 15 350 27 ALTERED DYNAMICS OF LIPID METABOLISM IN MUSCLE CELLS FROM PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY IS AMELIORATED BY 6 MONTHS OF TRAINING. KEY POINTS: REGULAR EXERCISE IMPROVES MUSCLE FUNCTIONAL CAPACITY AND CLINICAL STATE OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY (IIM). IN OUR STUDY, WE USED AN IN VITRO MODEL OF HUMAN PRIMARY MUSCLE CELL CULTURES, DERIVED FROM IIM PATIENTS BEFORE AND AFTER A 6-MONTH INTENSIVE SUPERVISED TRAINING INTERVENTION TO ASSESS THE IMPACT OF DISEASE AND EXERCISE ON LIPID METABOLISM DYNAMICS. WE PROVIDE EVIDENCE THAT MUSCLE CELLS FROM IIM PATIENTS DISPLAY ALTERED DYNAMICS OF LIPID METABOLISM AND IMPAIRED ADAPTIVE RESPONSE TO SATURATED FATTY ACID LOAD COMPARED TO HEALTHY CONTROLS. A 6-MONTH INTENSIVE SUPERVISED EXERCISE TRAINING INTERVENTION IN PATIENTS WITH IIM MITIGATED DISEASE EFFECTS IN THEIR CULTURED MUSCLE CELLS, IMPROVING OR NORMALIZING THEIR CAPACITY TO HANDLE LIPIDS. THESE FINDINGS HIGHLIGHT THE PUTATIVE ROLE OF INTRINSIC METABOLIC DEFECTS OF SKELETAL MUSCLE IN THE PATHOGENESIS OF IIM AND THE POSITIVE IMPACT OF EXERCISE, MAINTAINED IN VITRO BY YET UNKNOWN EPIGENETIC MECHANISMS. ABSTRACT: EXERCISE IMPROVES SKELETAL MUSCLE FUNCTION, CLINICAL STATE AND QUALITY OF LIFE IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY (IIM). OUR AIM WAS TO IDENTIFY DISEASE-RELATED METABOLIC PERTURBATIONS AND THE IMPACT OF EXERCISE IN SKELETAL MUSCLE CELLS OF IIM PATIENTS. PATIENTS UNDERWENT A 6-MONTH INTENSIVE SUPERVISED TRAINING INTERVENTION. MUSCLE FUNCTION, ANTHROPOMETRIC AND METABOLIC PARAMETERS WERE EXAMINED AND MUSCLE CELL CULTURES WERE ESTABLISHED (M. VASTUS LATERALIS; BERGSTROM NEEDLE BIOPSY) BEFORE AND AFTER TRAINING FROM PATIENTS AND SEDENTARY AGE/SEX/BODY MASS INDEX-MATCHED CONTROLS. [(14) C]PALMITATE WAS USED TO DETERMINE FAT OXIDATION AND LIPID SYNTHESIS (THIN LAYER CHROMATOGRAPHY). CELLS WERE EXPOSED TO A CHRONIC (3 DAYS) AND ACUTE (3 H) METABOLIC CHALLENGE (THE SATURATED FATTY ACID PALMITATE, 100 MUM). REDUCED OXIDATIVE (INTERMEDIATE METABOLITES, -49%, P = 0.034) AND NON-OXIDATIVE (DIGLYCERIDES, -38%, P = 0.013) LIPID METABOLISM WAS IDENTIFIED IN PALMITATE-TREATED MUSCLE CELLS FROM IIM PATIENTS COMPARED TO CONTROLS. THREE DAYS OF PALMITATE EXPOSURE ELICITED DISTINCT REGULATION OF OXIDATIVE PHOSPHORYLATION (OXPHOS) COMPLEX IV AND COMPLEX V/ATP SYNTHASE (P = 0.012/0.005) AND ADIPOSE TRIGLYCERIDE LIPASE IN PATIENTS COMPARED TO CONTROLS (P = 0.045) (IMMUNOBLOTTING). IMPORTANTLY, 6 MONTHS OF TRAINING IN IIM PATIENTS IMPROVED LIPID METABOLISM (CO(2) , P = 0.010; INTERMEDIATE METABOLITES, P = 0.041) AND ACTIVATION OF AMP KINASE (P = 0.007), AND NEARLY NORMALIZED PALMITATE-INDUCED CHANGES IN OXPHOS PROTEINS IN MYOTUBES FROM IIM PATIENTS, IN PARALLEL WITH IMPROVEMENTS OF PATIENTS' CLINICAL STATE. MYOTUBES FROM IIM PATIENTS DISPLAYED ALTERED DYNAMICS OF LIPID METABOLISM AND IMPAIRED RESPONSE TO METABOLIC CHALLENGE WITH SATURATED FATTY ACID. OUR OBSERVATIONS SUGGEST THAT METABOLIC DEFECTS INTRINSIC TO SKELETAL MUSCLE COULD REPRESENT NON-IMMUNE PATHOMECHANISMS, WHICH CAN CONTRIBUTE TO MUSCLE WEAKNESS IN IIM. A 6-MONTH TRAINING INTERVENTION MITIGATED DISEASE EFFECTS IN MUSCLE CELLS IN VITRO, INDICATING THE EXISTENCE OF EPIGENETIC REGULATORY MECHANISMS. 2021 16 1030 37 CIRCULATING PLASMA MICRORNAS DYSREGULATION AND METABOLIC ENDOTOXEMIA INDUCED BY A HIGH-FAT HIGH-SATURATED DIET. HIGH-FAT DIET INCREASE TWO TO THREE TIMES THE PLASMA LIPOPOLYSACCHARIDE (LPS) LEVELS AND INDUCE SUBCLINICAL INFLAMMATION. DIET CAN MODIFY GENE EXPRESSION DUE TO EPIGENETIC PROCESSES RELATED TO MICRORNAS (MIRNAS). MICRORNAS (MIRNAS) PLAY IMPORTANT ROLE IN THE POST-TRANSCRIPTIONAL MECHANISMS INVOLVED IN REGULATION OF EXPRESSION OF GENES RELATED TO THE INFLAMMATORY RESPONSE. ALSO, DIET CAN INDIRECTLY INDUCE POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION BY MIRNAS, WHICH MAY AFFECT THE RISK FOR THE DEVELOPMENT OF CHRONIC DISEASES. OBJECTIVE: THIS STUDY INVESTIGATED THE EFFECT OF HIGH-FAT HIGH-SATURATED MEAL INGESTION ON PLASMA MIRNA EXPRESSION AND LPS LEVELS DURING THE POSTPRANDIAL PERIOD IN HEALTHY WOMEN. METHODS: AN INTERVENTIONAL STUDY WAS CARRIED OUT IN WHICH A HIGH-FAT BREAKFAST (1067.45 KCAL), COMPOSED MAINLY OF SATURATED FATTY ACIDS (56 G), AND 500 ML OF WATER, WAS OFFERED. BLOOD SAMPLES WERE COLLECTED AT BASELINE AND 1, 3 AND 5 H AFTER MEAL INTAKE. THE STUDIED POPULATION CONSISTED OF HEALTHY WOMEN (N = 11), AGED BETWEEN 20 AND 40 YEARS, AND BODY MASS INDEX (BMI) BETWEEN 18.5 AND 25 KG/M(2). PLASMA LEVELS OF LIPID PROFILE, CYTOKINES, ADHESION MOLECULES, AND LPS WERE MEASURED AT THE 3 TIME POINTS. A PROFILE OF 752 HUMAN PLASMA MIRNA EXPRESSION WAS ANALYZED BY REAL-TIME PCR ASSAY. THESE ANALYZES WERE PERFORMED FOR ALL BLOOD COLLECTION TIME-POINTS. RESULTS: EXPRESSION PROFILE ANALYSIS REVEALED 33 DIFFERENTIALLY EXPRESSED PLASMA CIRCULATING MIRNAS COMPARED TO THAT OF THE CONTROL GROUP. MIR-145-5P AND MIR-200 WERE DIFFERENTIALLY MODULATED IN ALL TIME-POINTS POST MEAL CONSUMPTION. IN ADDITION, THERE WAS A SIGNIFICANT INCREASE IN PLASMA LPS, TRIGLYCERIDES, MYRISTIC AND PALMITIC SATURATED FATTY ACIDS LEVELS AT THE 3 TIME-POINTS IN COMPARISON WITH THE CONTROL BASAL LEVELS. WE ALSO OBSERVED INCREASED LEVELS OF THE PLASMA TUMOR NECROSIS FACTOR ALPHA (TNF-ALPHA) CYTOKINE AND THE VASCULAR CELL ADHESION MOLECULE 1 (VCAM-1) LEVELS AFTER 5 H POST MEAL INGESTION. CONCLUSION: INGESTION OF HIGH-FAT HIGH-SATURATED MEAL WAS ABLE TO INDUCE METABOLIC ENDOTOXEMIA AND INCREASE THE EXPRESSION OF PRO-INFLAMMATORY MOLECULES SUCH AS TNF-ALPHA AND VCAM-1, AS WELL AS MODULATING CIRCULATING MIRNAS POSSIBLY CONTROLLING INFLAMMATORY AND LIPID METABOLISM PROTEINS AT THE POSTPRANDIAL PERIOD. 2020 17 4205 40 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 18 5074 30 PHYSIOLOGIC AND EPIGENETIC EFFECTS OF NUTRIENTS ON DISEASE PATHWAYS. BACKGROUND/OBJECTIVES: EPIGENETIC REGULATION BY NUTRIENTS CAN INFLUENCE THE DEVELOPMENT OF SPECIFIC DISEASES. THIS STUDY SOUGHT TO EXAMINE THE EFFECT OF INDIVIDUAL NUTRIENTS AND NUTRIENT FAMILIES IN THE CONTEXT OF PREVENTING CHRONIC METABOLIC DISEASES VIA EPIGENETIC REGULATION. THE INHIBITION OF LIPID ACCUMULATION AND INFLAMMATION BY NUTRIENTS INCLUDING PROTEINS, LIPIDS, VITAMINS, AND MINERALS WERE OBSERVED, AND HISTONE ACETYLATION BY HISTONE ACETYLTRANSFERASE (HAT) WAS MEASURED. CORRELATIVE ANALYSES WERE ALSO PERFORMED. MATERIALS/METHODS: NUTRIENTS WERE SELECTED ACCORDING TO INFORMATION FROM THE KOREAN MINISTRY OF FOOD AND DRUG SAFETY. SELECTED NUTRIENT FUNCTIONALITIES, INCLUDING THE ATTENUATION OF FATTY ACID-INDUCED LIPID ACCUMULATION AND LIPOPOLYSACCHARIDE-MEDIATED ACUTE INFLAMMATION WERE EVALUATED IN MOUSE MACROPHAGE RAW264.7 AND MOUSE HEPATOCYTE AML-12 CELLS. EFFECTS OF THE SELECTED NUTRIENTS ON IN VITRO HAT INHIBITION WERE ALSO EVALUATED. RESULTS: NITRIC OXIDE (NO) PRODUCTION CORRELATED WITH HAT ACTIVITY, WHICH WAS REGULATED BY THE AMINO ACIDS GROUP, SUGGESTING THAT AMINO ACIDS POTENTIALLY CONTRIBUTE TO THE ATTENUATION OF NO PRODUCTION VIA THE INHIBITION OF HAT ACTIVITY. UNSATURATED FATTY ACIDS TENDED TO ATTENUATE INFLAMMATION BY INHIBITING NO PRODUCTION, WHICH MAY BE ATTRIBUTABLE TO THE INHIBITION OF IN VITRO HAT ACTIVITY. IN CONTRAST TO WATER-SOLUBLE VITAMINS, THE LIPID-SOLUBLE VITAMINS SIGNIFICANTLY DECREASED NO PRODUCTION. WATER- AND LIPID-SOLUBLE VITAMINS BOTH EXHIBITED SIGNIFICANT INHIBITORY ACTIVITIES AGAINST HAT. IN ADDITION, CALCIUM AND MANGANESE SIGNIFICANTLY INHIBITED LIPID ACCUMULATION, NO PRODUCTION, AND HAT ACTIVITY. CONCLUSIONS: SEVERAL CANDIDATE NUTRIENTS AND THEIR FAMILY MEMBERS MAY HAVE ROLES IN THE PREVENTION OF DISEASES, INCLUDING HEPATIC STEATOSIS AND INFLAMMATION-RELATED DISEASES (I.E., NONALCOHOLIC STEATOHEPATITIS) VIA EPIGENETIC REGULATION. FURTHER STUDIES ARE WARRANTED TO DETERMINE WHICH SPECIFIC AMINO ACIDS, UNSATURATED FATTY ACIDS AND LIPID-SOLUBLE VITAMINS OR SPECIFIC MINERALS INFLUENCE THE DEVELOPMENT OF STEATOSIS AND INFLAMMATORY-RELATED DISEASES. 2023 19 5112 24 POLYUNSATURATED FATTY ACIDS: BIOCHEMICAL, NUTRITIONAL AND EPIGENETIC PROPERTIES. DIETARY POLYUNSATURATED FATTY ACIDS (PUFA) HAVE EFFECTS ON DIVERSE PHYSIOLOGICAL PROCESSES IMPACTING NORMAL HEALTH AND CHRONIC DISEASES, SUCH AS THE REGULATION OF PLASMA LIPID LEVELS, CARDIOVASCULAR AND IMMUNE FUNCTION, INSULIN ACTION AND NEURONAL DEVELOPMENT AND VISUAL FUNCTION. INGESTION OF PUFA WILL LEAD TO THEIR DISTRIBUTION TO VIRTUALLY EVERY CELL IN THE BODY WITH EFFECTS ON MEMBRANE COMPOSITION AND FUNCTION, EICOSANOID SYNTHESIS, CELLULAR SIGNALING AND REGULATION OF GENE EXPRESSION. CELL SPECIFIC LIPID METABOLISM, AS WELL AS THE EXPRESSION OF FATTY ACID-REGULATED TRANSCRIPTION FACTORS, LIKELY PLAY AN IMPORTANT ROLE IN DETERMINING HOW CELLS RESPOND TO CHANGES IN PUFA COMPOSITION. THIS REVIEW WILL FOCUS ON RECENT ADVANCES ON THE ESSENTIALITY OF THESE MOLECULES AND ON THEIR INTERPLAY IN CELL PHYSIOLOGY, LEADING TO NEW PERSPECTIVE IN DIFFERENT THERAPEUTIC FIELDS. 2004 20 701 28 BROWN FAT DNMT3B DEFICIENCY AMELIORATES OBESITY IN FEMALE MICE. OBESITY RESULTS FROM A CHRONIC ENERGY IMBALANCE DUE TO ENERGY INTAKE EXCEEDING ENERGY EXPENDITURE. ACTIVATION OF BROWN FAT THERMOGENESIS HAS BEEN SHOWN TO COMBAT OBESITY. EPIGENETIC REGULATION, INCLUDING DNA METHYLATION, HAS EMERGED AS A KEY REGULATOR OF BROWN FAT THERMOGENIC FUNCTION. HERE WE AIMED TO STUDY THE ROLE OF DNMT3B, A DNA METHYLTRANSFERASE INVOLVED IN DE NOVO DNA METHYLATION, IN THE REGULATION OF BROWN FAT THERMOGENESIS AND OBESITY. WE FOUND THAT THE SPECIFIC DELETION OF DNMT3B IN BROWN FAT PROMOTES THE THERMOGENIC AND MITOCHONDRIAL PROGRAM IN BROWN FAT, ENHANCES ENERGY EXPENDITURE, AND DECREASES ADIPOSITY IN FEMALE MICE FED A REGULAR CHOW DIET. WITH A LEAN PHENOTYPE, THE FEMALE KNOCKOUT MICE ALSO EXHIBIT INCREASED INSULIN SENSITIVITY. IN ADDITION, DNMT3B DEFICIENCY IN BROWN FAT ALSO PREVENTS DIET-INDUCED OBESITY AND INSULIN RESISTANCE IN FEMALE MICE. INTERESTINGLY, OUR RNA-SEQ ANALYSIS REVEALED AN UPREGULATION OF THE PI3K-AKT PATHWAY IN THE BROWN FAT OF FEMALE DNMT3B KNOCKOUT MICE. HOWEVER, MALE DNMT3B KNOCKOUT MICE HAVE NO CHANGE IN THEIR BODY WEIGHT, SUGGESTING THE EXISTENCE OF SEXUAL DIMORPHISM IN THE BROWN FAT DNMT3B KNOCKOUT MODEL. OUR DATA DEMONSTRATE THAT DNMT3B PLAYS AN IMPORTANT ROLE IN THE REGULATION OF BROWN FAT FUNCTION, ENERGY METABOLISM AND OBESITY IN FEMALE MICE. 2021