1 1183 116 CONVERGING RELATIONSHIPS OF OBESITY AND HYPERURICEMIA WITH SPECIAL REFERENCE TO METABOLIC DISORDERS AND PLAUSIBLE THERAPEUTIC IMPLICATIONS. BACKGROUND: OBESITY AND HYPERURICEMIA MUTUALLY INFLUENCE METABOLIC SYNDROME. THIS STUDY DISCUSSES THE METABOLIC RELATIONSHIPS BETWEEN OBESITY AND HYPERURICEMIA IN TERMS OF PATHOPHYSIOLOGY, COMPLICATIONS, AND TREATMENTS. METHODS: WE SEARCHED FOR PRECLINICAL OR CLINICAL STUDIES ON THE PATHOPHYSIOLOGY, COMPLICATIONS, AND THERAPY OF OBESITY AND HYPERURICEMIA ON THE PUBMED DATABASE. RESULTS: IN THIS SYSTEMIC REVIEW, WE SUMMARIZED OUR SEARCHING RESULTS ON TOPICS OF PATHOPHYSIOLOGY, COMPLICATIONS AND THERAPEUTIC STRATEGY. IN PATHOPHYSIOLOGY, WE FIRSTLY INTRODUCE GENETIC VARIATIONS FOR OBESITY, HYPERURICEMIA AND THEIR RELATIONSHIPS BY GENETIC STUDIES. SECONDLY, WE TALK ABOUT THE EPIGENETIC INFLUENCES ON OBESITY AND HYPERURICEMIA. THIRDLY, WE DESCRIBE THE CENTRAL METABOLIC REGULATION AND THE ROLE OF HYPERURICEMIA. THEN, WE REFER TO THE CHARACTER OF ADIPOSE TISSUE INFLAMMATION AND OXIDATIVE STRESS IN THE OBESITY AND HYPERURICEMIA. IN THE LAST PART OF THIS TOPIC, WE REVIEWED THE CRITICAL LINKS OF GUT MICROBIOTA IN THE OBESITY AND HYPERURICEMIA. IN THE FOLLOWING PART, WE REVIEW THE PATHOPHYSIOLOGY OF MAJOR COMPLICATIONS IN OBESITY AND HYPERURICEMIA INCLUDING INSULIN RESISTANCE AND TYPE 2 DIABETES MELLITUS, CHRONIC KIDNEY DISEASE, CARDIOVASCULAR DISEASES, AND CANCERS. FINALLY, WE RECAPITULATE THE THERAPEUTIC STRATEGIES ESPECIALLY THE NOVEL PHARMACEUTIC INTERVENTIONS FOR OBESITY AND HYPERURICEMIA, WHICH CONCURRENTLY SHOW THE MUTUAL METABOLIC INFLUENCES BETWEEN TWO DISEASES. CONCLUSION: THE DATA REVIEWED HERE DELINEATE THE METABOLIC RELATIONSHIPS BETWEEN OBESITY AND HYPERURICEMIA, AND PROVIDE A COMPREHENSIVE OVERVIEW OF THE THERAPEUTIC TARGETS FOR THE MANAGEMENT OF METABOLIC SYNDROMES. 2020 2 5821 38 STRESS IN OBESITY AND ASSOCIATED METABOLIC AND CARDIOVASCULAR DISORDERS. OBESITY HAS SIGNIFICANT IMPLICATIONS FOR HEALTHCARE, SINCE IT IS A MAJOR RISK FACTOR FOR BOTH TYPE 2 DIABETES AND THE METABOLIC SYNDROME. THIS SYNDROME IS A COMMON AND COMPLEX DISORDER COMBINING OBESITY, DYSLIPIDEMIA, HYPERTENSION, AND INSULIN RESISTANCE. IT IS ASSOCIATED WITH HIGH ATHEROSCLEROTIC CARDIOVASCULAR RISK, WHICH CAN ONLY PARTIALLY BE EXPLAINED BY ITS COMPONENTS. THEREFORE, TO EXPLAIN HOW OBESITY CONTRIBUTES TO THE DEVELOPMENT OF METABOLIC AND CARDIOVASCULAR DISORDERS, MORE AND BETTER INSIGHT IS REQUIRED INTO THE EFFECTS OF PERSONAL AND ENVIRONMENTAL STRESS ON DISEASE PROCESSES. IN THIS PAPER, WE SHOW THAT OBESITY IS A CHRONIC INFLAMMATORY DISEASE, WHICH HAS MANY MOLECULAR MECHANISMS IN COMMON WITH ATHEROSCLEROSIS. FURTHERMORE, WE FOCUS ON THE ROLE OF OXIDATIVE STRESS ASSOCIATED WITH OBESITY IN THE DEVELOPMENT OF THE METABOLIC SYNDROME. WE DISCUSS HOW SEVERAL STRESS CONDITIONS ARE RELATED TO INFLAMMATION AND OXIDATIVE STRESS IN ASSOCIATION WITH OBESITY AND ITS COMPLICATIONS. WE ALSO EMPHASIZE THE RELATION BETWEEN STRESS CONDITIONS AND THE DEREGULATION OF EPIGENETIC CONTROL MECHANISMS BY MEANS OF MICRORNAS AND SHOW HOW THIS IMPAIRMENT FURTHER CONTRIBUTES TO THE DEVELOPMENT OF OBESITY, CLOSING THE VICIOUS CIRCLE. FINALLY, WE DISCUSS THE LIMITATIONS OF CURRENT ANTI-INFLAMMATION AND ANTIOXIDANT THERAPY TO TREAT OBESITY. 2012 3 6204 39 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023 4 6067 38 THE DIABETES MELLITUS-ATHEROSCLEROSIS CONNECTION: THE ROLE OF LIPID AND GLUCOSE METABOLISM AND CHRONIC INFLAMMATION. DIABETES MELLITUS COMPRISES A GROUP OF CARBOHYDRATE METABOLISM DISORDERS THAT SHARE A COMMON MAIN FEATURE OF CHRONIC HYPERGLYCEMIA THAT RESULTS FROM DEFECTS OF INSULIN SECRETION, INSULIN ACTION, OR BOTH. INSULIN IS AN IMPORTANT ANABOLIC HORMONE, AND ITS DEFICIENCY LEADS TO VARIOUS METABOLIC ABNORMALITIES IN PROTEINS, LIPIDS, AND CARBOHYDRATES. ATHEROSCLEROSIS DEVELOPS AS A RESULT OF A MULTISTEP PROCESS ULTIMATELY LEADING TO CARDIOVASCULAR DISEASE ASSOCIATED WITH HIGH MORBIDITY AND MORTALITY. ALTERATION OF LIPID METABOLISM IS A RISK FACTOR AND CHARACTERISTIC FEATURE OF ATHEROSCLEROSIS. POSSIBLE LINKS BETWEEN THE TWO CHRONIC DISORDERS DEPENDING ON ALTERED METABOLIC PATHWAYS HAVE BEEN INVESTIGATED IN NUMEROUS STUDIES. IT WAS SHOWN THAT BOTH TYPES OF DIABETES MELLITUS CAN ACTUALLY INDUCE ATHEROSCLEROSIS DEVELOPMENT OR FURTHER ACCELERATE ITS PROGRESSION. ELEVATED GLUCOSE LEVEL, DYSLIPIDEMIA, AND OTHER METABOLIC ALTERATIONS THAT ACCOMPANY THE DISEASE DEVELOPMENT ARE TIGHTLY INVOLVED IN THE PATHOGENESIS OF ATHEROSCLEROSIS AT ALMOST EVERY STEP OF THE ATHEROGENIC PROCESS. CHRONIC INFLAMMATION IS CURRENTLY CONSIDERED AS ONE OF THE KEY FACTORS IN ATHEROSCLEROSIS DEVELOPMENT AND IS PRESENT STARTING FROM THE EARLIEST STAGES OF THE PATHOLOGY INITIATION. IT MAY ALSO BE REGARDED AS ONE OF THE POSSIBLE LINKS BETWEEN ATHEROSCLEROSIS AND DIABETES MELLITUS. HOWEVER, THE DATA AVAILABLE SO FAR DO NOT ALLOW FOR DEVELOPING EFFECTIVE ANTI-INFLAMMATORY THERAPEUTIC STRATEGIES THAT WOULD STOP ATHEROSCLEROTIC LESION PROGRESSION OR INDUCE LESION REDUCTION. IN THIS REVIEW, WE SUMMARIZE THE MAIN ASPECTS OF DIABETES MELLITUS THAT POSSIBLY AFFECT THE ATHEROGENIC PROCESS AND ITS RELATIONSHIP WITH CHRONIC INFLAMMATION. WE ALSO DISCUSS THE ESTABLISHED PATHOPHYSIOLOGICAL FEATURES THAT LINK ATHEROSCLEROSIS AND DIABETES MELLITUS, SUCH AS OXIDATIVE STRESS, ALTERED PROTEIN KINASE SIGNALING, AND THE ROLE OF CERTAIN MIRNA AND EPIGENETIC MODIFICATIONS. 2020 5 5558 22 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 6 6607 41 TYPE 2 DIABETES MELLITUS AND CARDIOVASCULAR DISEASE: GENETIC AND EPIGENETIC LINKS. TYPE 2 DIABETES MELLITUS (DM) IS A COMMON METABOLIC DISORDER PREDISPOSING TO DIABETIC CARDIOMYOPATHY AND ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (CVD), WHICH COULD LEAD TO HEART FAILURE THROUGH A VARIETY OF MECHANISMS, INCLUDING MYOCARDIAL INFARCTION AND CHRONIC PRESSURE OVERLOAD. PATHOGENETIC MECHANISMS, MAINLY LINKED TO HYPERGLYCEMIA AND CHRONIC SUSTAINED HYPERINSULINEMIA, INCLUDE CHANGES IN METABOLIC PROFILES, INTRACELLULAR SIGNALING PATHWAYS, ENERGY PRODUCTION, REDOX STATUS, INCREASED SUSCEPTIBILITY TO ISCHEMIA, AND EXTRACELLULAR MATRIX REMODELING. THE CLOSE RELATIONSHIP BETWEEN TYPE 2 DM AND CVD HAS LED TO THE COMMON SOIL HYPOTHESIS, POSTULATING THAT BOTH CONDITIONS SHARE COMMON GENETIC AND ENVIRONMENTAL FACTORS INFLUENCING THIS ASSOCIATION. HOWEVER, ALTHOUGH THE COMMON RISK FACTORS OF BOTH CVD AND TYPE 2 DM, SUCH AS OBESITY, INSULIN RESISTANCE, DYSLIPIDEMIA, INFLAMMATION, AND THROMBOPHILIA, CAN BE IDENTIFIED IN THE MAJORITY OF AFFECTED PATIENTS, LESS IS KNOWN ABOUT HOW THESE FACTORS INFLUENCE BOTH CONDITIONS, SO THAT EFFORTS ARE STILL NEEDED FOR A MORE COMPREHENSIVE UNDERSTANDING OF THIS RELATIONSHIP. THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL BACKGROUNDS OF BOTH TYPE 2 DM AND CVD HAVE BEEN MORE RECENTLY STUDIED AND UPDATED. HOWEVER, THE UNDERLYING PATHOGENETIC MECHANISMS HAVE SELDOM BEEN INVESTIGATED WITHIN THE BROADER SHARED BACKGROUND, BUT RATHER STUDIED IN THE SPECIFIC CONTEXT OF TYPE 2 DM OR CVD, SEPARATELY. AS THE PRECISE PATHOPHYSIOLOGICAL LINKS BETWEEN TYPE 2 DM AND CVD ARE NOT ENTIRELY UNDERSTOOD AND MANY ASPECTS STILL REQUIRE ELUCIDATION, AN INTEGRATED DESCRIPTION OF THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL INFLUENCES INVOLVED IN THE CONCOMITANT DEVELOPMENT OF BOTH DISEASES IS OF PARAMOUNT IMPORTANCE TO SHED NEW LIGHT ON THE INTERLINKS BETWEEN TYPE 2 DM AND CVD. THIS REVIEW ADDRESSES THE CURRENT KNOWLEDGE OF OVERLAPPING GENETIC AND EPIGENETIC ASPECTS IN TYPE 2 DM AND CVD, INCLUDING MICRORNAS AND LONG NON-CODING RNAS, WHOSE ABNORMAL REGULATION HAS BEEN IMPLICATED IN BOTH DISEASE CONDITIONS, EITHER ETIOLOGICALLY OR AS CAUSE FOR THEIR PROGRESSION. UNDERSTANDING THE LINKS BETWEEN THESE DISORDERS MAY HELP TO DRIVE FUTURE RESEARCH TOWARD AN INTEGRATED PATHOPHYSIOLOGICAL APPROACH AND TO PROVIDE FUTURE DIRECTIONS IN THE FIELD. 2018 7 5076 37 PHYSIOLOGICAL AND ENVIRONMENTAL FACTORS AFFECTING CANCER RISK AND PROGNOSIS IN OBESITY. OBESITY RESULTS FROM A CHRONIC EXCESSIVE ACCUMULATION OF ADIPOSE TISSUE DUE TO A LONG-TERM IMBALANCE BETWEEN ENERGY INTAKE AND EXPENDITURE. AVAILABLE EPIDEMIOLOGICAL AND CLINICAL DATA STRONGLY SUPPORT THE LINKS BETWEEN OBESITY AND CERTAIN CANCERS. EMERGING CLINICAL AND EXPERIMENTAL FINDINGS HAVE IMPROVED OUR UNDERSTANDING OF THE ROLES OF KEY PLAYERS IN OBESITY-ASSOCIATED CARCINOGENESIS SUCH AS AGE, SEX (MENOPAUSE), GENETIC AND EPIGENETIC FACTORS, GUT MICROBIOTA AND METABOLIC FACTORS, BODY SHAPE TRAJECTORY OVER LIFE, DIETARY HABITS, AND GENERAL LIFESTYLE. IT IS NOW WIDELY ACCEPTED THAT THE CANCER-OBESITY RELATIONSHIP DEPENDS ON THE SITE OF CANCER, THE SYSTEMIC INFLAMMATORY STATUS, AND MICRO ENVIRONMENTAL PARAMETERS SUCH AS LEVELS OF INFLAMMATION AND OXIDATIVE STRESS IN TRANSFORMING TISSUES. WE HEREBY REVIEW RECENT ADVANCES IN OUR UNDERSTANDING OF CANCER RISK AND PROGNOSIS IN OBESITY WITH RESPECT TO THESE PLAYERS. WE HIGHLIGHT HOW THE LACK OF THEIR CONSIDERATION CONTRIBUTED TO THE CONTROVERSY OVER THE LINK BETWEEN OBESITY AND CANCER IN EARLY EPIDEMIOLOGICAL STUDIES. FINALLY, THE LESSONS AND CHALLENGES OF INTERVENTIONS FOR WEIGHT LOSS AND BETTER CANCER PROGNOSIS, AND THE MECHANISMS OF WEIGHT GAIN IN SURVIVORS ARE ALSO DISCUSSED. 2023 8 4662 28 NEW DEVELOPMENTS IN THE PATHOGENESIS OF OBESITY-INDUCED HYPERTENSION. OBESITY IS A DISORDER THAT DEVELOPS FROM THE INTERACTION BETWEEN GENOTYPE AND ENVIRONMENT INVOLVING SOCIAL, BEHAVIORAL, CULTURAL, AND PHYSIOLOGICAL FACTORS. OBESITY INCREASES THE RISK FOR TYPE 2 DIABETES MELLITUS, HYPERTENSION, CARDIOVASCULAR DISEASE, CANCER, MUSCULOSKELETAL DISORDERS, CHRONIC KIDNEY AND PULMONARY DISEASE. ALTHOUGH OBESITY IS CLEARLY ASSOCIATED WITH AN INCREASED PREVALENCE OF HYPERTENSION, MANY OBESE INDIVIDUALS MAY NOT DEVELOP HYPERTENSION. PROTECTING FACTORS MAY EXIST AND IT IS IMPORTANT TO UNDERSTAND WHY OBESITY IS NOT ALWAYS RELATED TO HYPERTENSION. THE AIM OF THIS REVIEW IS TO HIGHLIGHT THE KNOWLEDGE GAP FOR THE ASSOCIATION BETWEEN OBESITY, HYPERTENSION, AND POTENTIAL GENETIC AND RACIAL DIFFERENCES OR ENVIRONMENTAL FACTORS THAT MAY PROTECT OBESE PATIENTS AGAINST THE DEVELOPMENT OF HYPERTENSION AND OTHER CO-MORBIDITIES. SPECIFIC MUTATIONS IN THE LEPTIN AND THE MELANINOCORTIN RECEPTOR GENES IN ANIMAL MODELS OF OBESITY WITHOUT HYPERTENSION, THE ACTIONS OF ALPHA-MELANOCYTE STIMULATING HORMONE, AND SNS ACTIVITY IN OBESITY-RELATED HYPERTENSION MAY PROMOTE RECOGNITION OF PROTECTIVE AND PROMOTING FACTORS FOR HYPERTENSION IN OBESITY. FURTHERMORE, GENE-ENVIRONMENT INTERACTIONS MAY HAVE THE POTENTIAL TO MODIFY GENE EXPRESSION AND EPIGENETIC MECHANISMS COULD ALSO CONTRIBUTE TO THE HERITABILITY OF OBESITY-INDUCED HYPERTENSION. FINALLY, DIFFERENCES IN NUTRITION, GUT MICROBIOTA, EXPOSURE TO SUN LIGHT AND EXERCISE MAY PLAY AN IMPORTANT ROLE IN THE PRESENCE OR ABSENCE OF HYPERTENSION IN OBESITY. 2015 9 4425 45 MOLECULAR BASIS OF AGEING IN CHRONIC METABOLIC DISEASES. AIM: OVER THE LAST DECADES, THE SHIFT IN AGE DISTRIBUTION TOWARDS OLDER AGES AND THE PROGRESSIVE AGEING WHICH HAS OCCURRED IN MOST POPULATIONS HAVE BEEN PARALLELED BY A GLOBAL EPIDEMIC OF OBESITY AND ITS RELATED METABOLIC DISORDERS, PRIMARILY, TYPE 2 DIABETES (T2D). DYSFUNCTION OF THE ADIPOSE TISSUE (AT) IS WIDELY RECOGNIZED AS A SIGNIFICANT HALLMARK OF THE AGEING PROCESS THAT, IN TURN, RESULTS IN SYSTEMIC METABOLIC ALTERATIONS. THESE INCLUDE INSULIN RESISTANCE, ACCUMULATION OF ECTOPIC LIPIDS AND CHRONIC INFLAMMATION, WHICH ARE RESPONSIBLE FOR AN ELEVATED RISK OF OBESITY AND T2D ONSET ASSOCIATED TO AGEING. ON THE OTHER HAND, OBESITY AND T2D, THE PARADIGMS OF AT DYSFUNCTION, SHARE MANY PHYSIOLOGICAL CHARACTERISTICS WITH THE AGEING PROCESS, SUCH AS AN INCREASED BURDEN OF SENESCENT CELLS AND EPIGENETIC ALTERATIONS. THUS, THESE CHRONIC METABOLIC DISORDERS MAY REPRESENT A STATE OF ACCELERATED AGEING. MATERIALS AND METHODS: A MORE PRECISE EXPLANATION OF THE FUNDAMENTAL AGEING MECHANISMS THAT OCCUR IN AT AND A DEEPER UNDERSTANDING OF THEIR ROLE IN THE INTERPLAY BETWEEN ACCELERATED AGEING AND AT DYSFUNCTION CAN BE A FUNDAMENTAL LEAP TOWARDS NOVEL THERAPIES THAT ADDRESS THE CAUSES, NOT JUST THE SYMPTOMS, OF OBESITY AND T2D, UTILIZING STRATEGIES THAT TARGET EITHER SENESCENT CELLS OR DNA METHYLATION. RESULTS: IN THIS REVIEW, WE SUMMARIZE THE CURRENT KNOWLEDGE OF THE PATHWAYS THAT LEAD TO AT DYSFUNCTION IN THE CHRONOLOGICAL AGEING PROCESS AS WELL AS THE PATHOPHYSIOLOGY OF OBESITY AND T2D, EMPHASIZING THE CRITICAL ROLE OF CELLULAR SENESCENCE AND DNA METHYLATION. CONCLUSION: FINALLY, WE HIGHLIGHT THE NEED FOR FURTHER RESEARCH FOCUSED ON TARGETING THESE MECHANISMS. 2020 10 6380 29 THE ROLE OF OBESITY AND DIABETES IN DEMENTIA. CHRONIC CONDITIONS SUCH AS OBESITY, DIABETES, AND DEMENTIA ARE INCREASING IN THE UNITED STATES (US) POPULATION. KNOWLEDGE OF THESE CHRONIC CONDITIONS, PREVENTATIVE MEASURES, AND PROPER MANAGEMENT TACTICS IS IMPORTANT AND CRITICAL TO PREVENTING DISEASE. THE OVERLAP BETWEEN OBESITY, DIABETES, AND DEMENTIA IS BECOMING FURTHER ELUCIDATED. THESE CONDITIONS SHARE A SIMILAR ORIGIN THROUGH THE COMPONENTS OF INCREASING AGE, GENDER, GENETIC AND EPIGENETIC PREDISPOSITIONS, DEPRESSION, AND A HIGH-FAT WESTERN DIET (WD) THAT ALL CONTRIBUTE TO THE INFLAMMATORY STATE ASSOCIATED WITH THE DEVELOPMENT OF OBESITY, DIABETES, AND DEMENTIA. THIS INFLAMMATORY STATE LEADS TO THE DYSREGULATION OF FOOD INTAKE AND INSULIN RESISTANCE. OBESITY IS OFTEN THE CORNERSTONE THAT LEADS TO THE DEVELOPMENT OF DIABETES AND, SUBSEQUENTLY, IN THE CASE OF TYPE 2 DIABETES MELLITUS (T2DM), PROGRESSION TO "TYPE 3 DIABETES MELLITUS (T3DM)". OBESITY AND DEPRESSION ARE CLOSELY ASSOCIATED WITH DIABETES. HOWEVER, DEMENTIA CAN BE AVOIDED WITH LIFESTYLE MODIFICATIONS, BY SWITCHING TO A PLANT-BASED DIET (E.G., A MEDITERRANEAN DIET (MD)), AND INCREASING PHYSICAL ACTIVITY. DIET AND EXERCISE ARE NOT THE ONLY TREATMENT OPTIONS. THERE ARE SEVERAL SURGICAL AND PHARMACOLOGICAL INTERVENTIONS AVAILABLE FOR PREVENTION. CURRENT AND FUTURE RESEARCH WITHIN EACH OF THESE FIELDS IS WARRANTED AND OFFERS THE CHANCE FOR NEW TREATMENT OPTIONS AND A BETTER UNDERSTANDING OF THE PATHOGENESIS OF EACH CONDITION. 2022 11 6259 27 THE MOLECULAR MECHANISMS BY WHICH VITAMIN D PREVENTS INSULIN RESISTANCE AND ASSOCIATED DISORDERS. NUMEROUS STUDIES HAVE SHOWN THAT VITAMIN D DEFICIENCY IS VERY COMMON IN MODERN SOCIETIES AND IS PERCEIVED AS AN IMPORTANT RISK FACTOR IN THE DEVELOPMENT OF INSULIN RESISTANCE AND RELATED DISEASES SUCH AS OBESITY AND TYPE 2 DIABETES (T2DM). WHILE IT IS GENERALLY ACCEPTED THAT VITAMIN D IS A REGULATOR OF BONE HOMEOSTASIS, ITS ABILITY TO COUNTERACT INSULIN RESISTANCE IS SUBJECT TO DEBATE. THE GOAL OF THIS COMMUNICATION IS TO REVIEW THE MOLECULAR MECHANISM BY WHICH VITAMIN D REDUCES INSULIN RESISTANCE AND RELATED COMPLICATIONS. THE UNIVERSITY LIBRARY, PUBMED, AND GOOGLE SCHOLAR WERE SEARCHED TO FIND RELEVANT STUDIES TO BE SUMMARIZED IN THIS REVIEW ARTICLE. INSULIN RESISTANCE IS ACCOMPANIED BY CHRONIC HYPERGLYCAEMIA AND INFLAMMATION. RECENT STUDIES HAVE SHOWN THAT VITAMIN D EXHIBITS INDIRECT ANTIOXIDATIVE PROPERTIES AND PARTICIPATES IN THE MAINTENANCE OF NORMAL RESTING ROS LEVEL. APPEALINGLY, VITAMIN D REDUCES INFLAMMATION AND REGULATES CA(2+) LEVEL IN MANY CELL TYPES. THEREFORE, THE BENEFICIAL ACTIONS OF VITAMIN D INCLUDE DIMINISHED INSULIN RESISTANCE WHICH IS OBSERVED AS AN IMPROVEMENT OF GLUCOSE AND LIPID METABOLISM IN INSULIN-SENSITIVE TISSUES. 2020 12 44 32 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 13 2163 28 EPIGENETIC MECHANISMS IN DIABETIC VASCULAR COMPLICATIONS. THERE HAS BEEN A RAPID INCREASE IN THE INCIDENCE OF DIABETES AS WELL THE ASSOCIATED VASCULAR COMPLICATIONS. BOTH GENETIC AND ENVIRONMENTAL FACTORS HAVE BEEN IMPLICATED IN THESE PATHOLOGIES. INCREASING EVIDENCE SUGGESTS THAT EPIGENETIC FACTORS PLAY A KEY ROLE IN THE COMPLEX INTERPLAY BETWEEN GENES AND THE ENVIRONMENT. ACTIONS OF MAJOR PATHOLOGICAL MEDIATORS OF DIABETES AND ITS COMPLICATIONS SUCH AS HYPERGLYCAEMIA, OXIDANT STRESS, AND INFLAMMATORY FACTORS CAN LEAD TO DYSREGULATED EPIGENETIC MECHANISMS THAT AFFECT CHROMATIN STRUCTURE AND GENE EXPRESSION. FURTHERMORE, PERSISTENCE OF THIS ALTERED STATE OF THE EPIGENOME MAY BE THE UNDERLYING MECHANISM CONTRIBUTING TO A 'METABOLIC MEMORY' THAT RESULTS IN CHRONIC INFLAMMATION AND VASCULAR DYSFUNCTION IN DIABETES EVEN AFTER ACHIEVING GLYCAEMIC CONTROL. FURTHER EXAMINATION OF EPIGENETIC MECHANISMS BY ALSO TAKING ADVANTAGE OF RECENTLY DEVELOPED NEXT-GENERATION SEQUENCING TECHNOLOGIES CAN PROVIDE NOVEL INSIGHTS INTO THE PATHOLOGY OF DIABETES AND ITS COMPLICATIONS AND LEAD TO THE DISCOVERY OF MUCH NEEDED NEW DRUG TARGETS FOR THESE DISEASES. IN THIS REVIEW, WE HIGHLIGHT THE ROLE OF EPIGENETICS IN DIABETES AND ITS VASCULAR COMPLICATIONS, AND RECENT TECHNOLOGICAL ADVANCES THAT HAVE SIGNIFICANTLY ACCELERATED THE FIELD. 2011 14 5646 24 SEX DIFFERENCES AND EMERGING NEW RISK FACTORS FOR ATHEROSCLEROSIS AND ITS THROMBOTIC COMPLICATIONS. CARDIOVASCULAR DISEASES (CVD) REMAIN THE WORLD'S LEADING CAUSE OF DEATH AND DISABILITY IN BOTH MEN AND WOMEN, BUT WITH DIFFERENT PROGNOSTICS AND OUTCOMES BETWEEN SEXES. ALTHOUGH THE BURDEN OF CVD IS GENERALLY RELATED TO THE CONVENTIONAL RISK FACTORS, THE RELEVANCE OF NON-TRADITIONAL RISK FACTORS IS INCREASINGLY BEING RECOGNIZED TO EXPLAIN THE SO-CALLED "RESIDUAL RISK". MEN AND WOMEN SHARE MANY SIMILARITIES REGARDING CLASSICAL CARDIOVASCULAR RISK FACTORS BUT HAVE DIFFERENT DISEASE PATHOPHYSIOLOGY, CLINICAL PRESENTATIONS, PREVALENCE, AND OUTCOMES OF CVDS. HOW SEX-SPECIFICITIES REGARDING THE EFFECTS OF NON-TRADITIONAL RISK FACTORS MAY CONTRIBUTE TO THE EVOLUTION OF ATHEROSCLEROSIS AND ITS CLINICAL MANIFESTATIONS IN MALES AND FEMALES REMAIN LARGELY UNDERANALYZED. THE PRESENT REVIEW SUMMARIZES THE CURRENT KNOWLEDGE FOR SEX DIFFERENCES IN ATHEROSCLEROTIC PLAQUE COMPOSITION AND CLINICAL EVOLUTION IN ASSOCIATION WITH RISK FACTORS, SUCH AS INFLAMMATION, LIPOPROTEIN(A), HEMOSTASIS, INTRAPLAQUE CALCIFICATION, AND DEPRESSION. WE FURTHER DISCUSS THE POTENTIAL SEX-DIFFERENTIAL IMPACT OF CHRONIC INFECTIOUS DISEASES, GUT MICROBIOME AND, EPIGENETIC GENE EXPRESSION REGULATION FOR ATHEROSCLEROSIS AND THE EFFECT OF FEMALE-SPECIFIC DISORDERS IN CVD. 2021 15 2584 25 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 6462 38 TISSUE AND CIRCULATING MICRORNAS AS BIOMARKERS OF RESPONSE TO OBESITY TREATMENT STRATEGIES. BACKGROUND: OBESITY, CHARACTERIZED BY AN INCREASED AMOUNT OF ADIPOSE TISSUE, IS A METABOLIC CHRONIC ALTERATION WHICH HAS REACHED PANDEMIC PROPORTION. LIFESTYLE CHANGES ARE THE FIRST LINE THERAPY FOR OBESITY AND A LARGE VARIETY OF DIETARY APPROACHES HAVE DEMONSTRATED EFFICACY IN PROMOTING WEIGHT LOSS AND IMPROVING OBESITY-RELATED METABOLIC ALTERATIONS. BESIDES DIET AND PHYSICAL ACTIVITY, BARIATRIC SURGERY MIGHT BE AN EFFECTIVE THERAPEUTIC STRATEGY FOR MORBID OBESE PATIENTS. RESPONSE TO WEIGHT-LOSS INTERVENTIONS IS CHARACTERISED BY HIGH INTER-INDIVIDUAL VARIABILITY, WHICH MIGHT INVOLVE EPIGENETIC FACTORS. MICRORNAS HAVE CRITICAL ROLES IN METABOLIC PROCESSES AND THEIR DYSREGULATED EXPRESSION HAS BEEN REPORTED IN OBESITY. AIM: THE AIM OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF CURRENT STUDIES EVALUATING CHANGES IN MICRORNA EXPRESSION IN OBESE PATIENTS UNDERGOING LIFESTYLE INTERVENTIONS OR BARIATRIC SURGERY. RESULTS: A CONSIDERABLE NUMBER OF STUDIES HAVE REPORTED A DIFFERENTIAL EXPRESSION OF CIRCULATING MICRORNAS BEFORE AND AFTER VARIOUS DIETARY AND BARIATRIC SURGERY APPROACHES, IDENTIFYING SEVERAL CANDIDATE BIOMARKERS OF RESPONSE TO WEIGHT LOSS. SIGNIFICANT CHANGES IN MICRORNA EXPRESSION HAVE BEEN OBSERVED AT A TISSUE LEVEL AS WELL, WITH ENTIRELY DIFFERENT PATTERNS BETWEEN VISCERAL AND SUBCUTANEOUS ADIPOSE TISSUE. INTERESTINGLY, RELEVANT DIFFERENCES IN MICRORNA EXPRESSION HAVE EMERGED BETWEEN RESPONDERS AND NON-RESPONDERS TO DIETARY OR SURGICAL INTERVENTIONS. A WIDE VARIETY OF DYSREGULATED MICRORNA TARGET PATHWAYS HAVE ALSO BEEN IDENTIFIED, HELPING TO UNDERSTAND THE PATHOPHYSIOLOGICAL MECHANISMS UNDERLYING OBESITY AND OBESITY-RELATED METABOLIC DISEASES. CONCLUSIONS: ALTHOUGH FURTHER RESEARCH IS NEEDED TO DRAW FIRM CONCLUSIONS, THERE IS INCREASING EVIDENCE ABOUT MICRORNAS AS POTENTIAL BIOMARKERS FOR WEIGHT LOSS AND RESPONSE TO INTERVENTION STRATEGIES IN OBESITY. 2021 17 6165 25 THE GLOBAL DIABETES EPIDEMIC AS A CONSEQUENCE OF LIFESTYLE-INDUCED LOW-GRADE INFLAMMATION. THE RECENT MAJOR INCREASE IN THE GLOBAL INCIDENCE OF TYPE 2 DIABETES SUGGESTS THAT MOST CASES OF THIS DISEASE ARE CAUSED BY CHANGES IN ENVIRONMENT AND LIFESTYLE. ALL MAJOR RISK FACTORS FOR TYPE 2 DIABETES (OVERNUTRITION, LOW DIETARY FIBRE, SEDENTARY LIFESTYLE, SLEEP DEPRIVATION AND DEPRESSION) HAVE BEEN FOUND TO INDUCE LOCAL OR SYSTEMIC LOW-GRADE INFLAMMATION THAT IS USUALLY TRANSIENT OR MILDER IN INDIVIDUALS NOT AT RISK FOR TYPE 2 DIABETES. BY CONTRAST, INFLAMMATORY RESPONSES TO LIFESTYLE FACTORS ARE MORE PRONOUNCED AND PROLONGED IN INDIVIDUALS AT RISK OF TYPE 2 DIABETES AND APPEAR TO OCCUR ALSO IN THE PANCREATIC ISLETS. CHRONIC LOW-GRADE INFLAMMATION WILL EVENTUALLY LEAD TO OVERT DIABETES IF COUNTER-REGULATORY CIRCUITS TO INFLAMMATION AND METABOLIC STRESS ARE COMPROMISED BECAUSE OF A GENETIC AND/OR EPIGENETIC PREDISPOSITION. HENCE, IT IS NOT THE LIFESTYLE CHANGE PER SE BUT A DEFICIENT COUNTER-REGULATORY RESPONSE IN PREDISPOSED INDIVIDUALS WHICH IS CRUCIAL TO DISEASE PATHOGENESIS. NOVEL APPROACHES OF INTERVENTION MAY TARGET THESE DEFICIENT DEFENCE MECHANISMS. 2010 18 4273 28 MICROBIOTA AND EPIGENETICS: HEALTH IMPACT. EPIGENETIC CHANGES ASSOCIATED WITH DISEASE DEVELOPMENT AND PROGRESSIONS ARE OF INCREASING IMPORTANCE BECAUSE OF THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. SEVERAL EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC METABOLIC DISORDERS HAVE BEEN STUDIED IN VARIOUS DISEASES. EPIGENETIC CHANGES ARE MOSTLY MODULATED BY ENVIRONMENTAL FACTORS, INCLUDING THE HUMAN MICROBIOTA LIVING IN DIFFERENT PARTS OF OUR BODIES. THE MICROBIAL STRUCTURAL COMPONENTS AND THE MICROBIALLY DERIVED METABOLITES DIRECTLY INTERACT WITH HOST CELLS, THEREBY MAINTAINING HOMEOSTASIS. MICROBIOME DYSBIOSIS, ON THE OTHER HAND, IS KNOWN TO PRODUCE ELEVATED LEVELS OF DISEASE-LINKED METABOLITES, WHICH MAY DIRECTLY AFFECT A HOST METABOLIC PATHWAY OR INDUCE EPIGENETIC CHANGES THAT CAN LEAD TO DISEASE DEVELOPMENT. DESPITE THEIR IMPORTANT ROLE IN HOST PHYSIOLOGY AND SIGNAL TRANSDUCTION, THERE HAS BEEN LITTLE RESEARCH INTO THE MECHANICS AND PATHWAYS ASSOCIATED WITH EPIGENETIC MODIFICATIONS. THIS CHAPTER FOCUSES ON THE RELATIONSHIP BETWEEN MICROBES AND THEIR EPIGENETIC EFFECTS IN DISEASED PATHOLOGY, AS WELL AS ON THE REGULATION AND METABOLISM OF THE DIETARY OPTIONS AVAILABLE TO THE MICROBES. FURTHERMORE, THIS CHAPTER ALSO PROVIDES A PROSPECTIVE LINK BETWEEN THESE TWO IMPORTANT PHENOMENA, TERMED "MICROBIOME AND EPIGENETICS." 2023 19 2190 31 EPIGENETIC MECHANISMS. THE INCIDENCE OF DIABETES AND RELATED COMPLICATIONS LIKE NEPHROPATHY IS GROWING RAPIDLY AND HAS BECOME A MAJOR HEALTH CARE ISSUE. CHANGES IN THE ENVIRONMENT AND NUTRITIONAL HABITS HAVE BEEN IMPLICATED AS MAJOR PLAYERS. FURTHERMORE, IT IS BECOMING INCREASINGLY CLEAR THAT EPIGENETIC FACTORS MAY MODULATE THE CONNECTIONS BETWEEN GENES AND THE ENVIRONMENT. WHILE DIABETES IN ITSELF IS TREATABLE TO A LARGE EXTENT, IT IS STILL ASSOCIATED WITH SIGNIFICANTLY INCREASED RISK FOR COMPLICATIONS INCLUDING CHRONIC KIDNEY AND CARDIOVASCULAR DISEASES. CURRENT TREATMENTS HAVE ADDED PREVENTATIVE APPROACHES SO AS TO AVOID FUTURE DIABETIC COMPLICATIONS. UNFORTUNATELY, DIABETIC PATIENTS ARE OFTEN PLAGUED WITH THE CONTINUED DEVELOPMENT OF VARIOUS COMPLICATIONS EVEN AFTER ACHIEVING GLUCOSE CONTROL. THIS HAS BEEN SUGGESTED TO BE ATTRIBUTABLE TO A MYSTERIOUS PHENOMENON TERMED 'METABOLIC MEMORY' OF THE PRIOR GLYCEMIC STATE. RECENT STUDIES HAVE SUGGESTED THAT EPIGENETIC CHANGES TO CHROMATIN CAN AFFECT GENE EXPRESSION IN RESPONSE TO VARIOUS STIMULI, AND CHANGES IN KEY BIOCHEMICAL PATHWAYS AND EPIGENETIC HISTONE AND DNA METHYLATION PATTERNS IN CHROMATIN HAVE BEEN OBSERVED IN A DIABETIC MILIEU. THESE ACCUMULATING DATA SUGGEST THAT METABOLIC OR HYPERGLYCEMIC MEMORY MAY BE DUE TO EPIGENETIC CHANGES IN SPECIFIC TARGET TISSUES ALTERING GENE EXPRESSION WITHOUT CHANGING THE GENETIC CODE ITSELF. WHILE THE GENETICS OF DIABETES HAS LONG BEEN THE FOCUS OF SCIENTIFIC RESEARCH, MUCH LESS IS KNOWN ABOUT THE ROLE OF EPIGENETICS AND THE RELATED MOLECULAR PATHWAYS THAT MIGHT AFFECT THE DEVELOPMENT OF DIABETES AND THE ASSOCIATED COMPLICATIONS. FURTHER STUDIES OF EPIGENETIC MECHANISMS ARE THEREFORE TIMELY AND COULD PROVIDE VALUABLE NEW INSIGHTS INTO THE PATHOLOGY OF DIABETIC COMPLICATIONS AND ALSO UNCOVER MUCH NEEDED NEW THERAPEUTIC TARGETS. 2011 20 1871 26 EMERGING ROLE OF EPIGENETICS IN EXPLAINING RELATIONSHIP OF PERIODONTITIS AND CARDIOVASCULAR DISEASES. CARDIOVASCULAR DISEASES SUCH AS ISCHEMIC HEART DISEASES OR STROKE ARE AMONG THE LEADING CAUSE OF DEATHS GLOBALLY, AND EVIDENCE SUGGESTS THAT THESE DISEASES ARE MODULATED BY A MULTIFACTORIAL AND COMPLEX INTERPLAY OF GENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS. GENETIC PREDISPOSITION AND CHRONIC EXPOSURE TO MODIFIABLE RISK FACTORS HAVE BEEN EXPLORED TO BE INVOLVED IN THE PATHOPHYSIOLOGY OF CVD. ENVIRONMENTAL FACTORS CONTRIBUTE TO AN INDIVIDUAL'S PROPENSITY TO DEVELOP MAJOR CARDIOVASCULAR RISK FACTORS THROUGH EPIGENETIC MODIFICATIONS OF DNA AND HISTONES VIA MIRNA REGULATION OF PROTEIN TRANSLATION THAT ARE TYPES OF EPIGENETIC MECHANISMS AND PARTICIPATE IN DISEASE DEVELOPMENT. PERIODONTAL DISEASE (PD) IS ONE OF THE MOST COMMON ORAL DISEASES IN HUMANS THAT IS CHARACTERIZED BY LOW-GRADE INFLAMMATION AND HAS BEEN SHOWN TO INCREASE THE RISK OF CVDS. RISK FACTORS INVOLVED IN PD AND CVD ARE DETERMINED BOTH GENETICALLY AND BEHAVIORALLY. PERIODONTAL DISEASES SUCH AS CHRONIC INFLAMMATION PROMOTE DNA METHYLATION. EPIGENETIC MODIFICATIONS INVOLVED IN THE INITIATION AND PROGRESSION OF ATHEROSCLEROSIS PLAY AN ESSENTIAL ROLE IN PLAQUE DEVELOPMENT AND VULNERABILITY. EPIGENETICS HAS OPENED A NEW WORLD TO UNDERSTAND AND MANAGE HUMAN DISEASES, INCLUDING CVDS AND PERIODONTAL DISEASES. GENETIC MEDICINE HAS STARTED A NEW ERA OF EPIGENETICS TO OVERCOME HUMAN DISEASES WITH VARIOUS NEW METHODOLOGY. EPIGENETIC PROFILING MAY AID IN BETTER DIAGNOSIS AND STRATIFICATION OF PATIENTS SHOWING POTENTIAL PREDISPOSED STATES FOR DISEASE. A BETTER UNDERSTANDING OF THE EXACT REGULATORY MECHANISMS OF EPIGENETIC PATHWAYS DRIVING INFLAMMATION IS SLOWLY EMERGING AND WILL AID IN DEVELOPING NOVEL TOOLS FOR THE TREATMENT OF DISEASE. 2021