1 6469 178 TISSUE-SPECIFIC METHYLATION PROFILE IN OBESE PATIENTS WITH TYPE 2 DIABETES BEFORE AND AFTER ROUX-EN-Y GASTRIC BYPASS. EATING HABITS, LIFESTYLES, AND EXPOSURE TO SPECIFIC ENVIRONMENTAL FACTORS CAN GREATLY IMPACT THE RISK OF DEVELOPING TYPE 2 DIABETES (T2D), INFLUENCE THE GENOME EPIGENETICALLY, AND AFFECT THE EXPRESSION OF GENES, INCLUDING GENES RELATED TO GLYCEMIC CONTROL, AT ANY STAGE OF LIFE. THE EPIGENETIC MECHANISM UNDERLYING OBESITY AND T2D PATHOGENESIS REMAINS POORLY UNDERSTOOD. CONVENTIONAL STRATEGIES FOR THE TREATMENT OF OBESITY AND ITS COMORBIDITIES OFTEN HAVE POOR LONG-TERM ADHERENCE, AND PHARMACOLOGICAL INTERVENTIONS ARE LIMITED. BARIATRIC SURGERY IS THE MOST EFFECTIVE CURRENT OPTION TO TREAT SEVERE OBESITY, AND ROUX-EN-Y GASTRIC BYPASS (RYGB) IS THE MOST APPLIED TECHNIQUE WORLDWIDE. EPIGENETIC CHANGES DIFFER DEPENDING ON THE APPROACH USED TO TREAT OBESITY AND ITS ASSOCIATED COMORBIDITIES (CLINICAL OR SURGICAL). COMPARED TO PRIMARY CLINICAL CARE, BARIATRIC SURGERY LEADS TO MUCH GREATER LOSS OF BODY WEIGHT AND HIGHER REMISSION RATES OF T2D AND METABOLIC SYNDROME, WITH METHYLATION PROFILES IN PROMOTER REGIONS OF GENES IN OBESE INDIVIDUALS BECOMING SIMILAR TO THOSE OF NORMAL-WEIGHT INDIVIDUALS. BARIATRIC SURGERY CAN INFLUENCE DNA METHYLATION IN PARALLEL WITH CHANGES IN GENE EXPRESSION PATTERN. CHANGES IN CLINICAL BIOMARKERS THAT REFLECT IMPROVEMENTS IN GLUCOSE AND LIPID METABOLISM AFTER RYGB OFTEN OCCUR BEFORE MAJOR WEIGHT LOSS AND ARE COORDINATED BY SURGERY-INDUCED CHANGES IN INTESTINAL HORMONES. THEREFORE, THE INTESTINE METHYLATION PROFILE WOULD ASSIST IN UNDERSTANDING THE MECHANISMS INVOLVED IN IMPROVED GLYCEMIC CONTROL AFTER BARIATRIC SURGERY. THE MAIN OBJECTIVES IN THIS AREA FOR THE FUTURE ARE TO IDENTIFY EPIGENETIC MARKS THAT COULD BE USED AS EARLY INDICATORS OF METABOLIC RISK, AND TO DEVELOP TREATMENTS ABLE TO DELAY OR EVEN REVERSE THESE EPIGENETIC CHANGES. STUDIES THAT PROVIDE THE "HUMAN EPIGENETIC PROFILE" WILL BE OF CONSIDERABLE VALUE TO IDENTIFY TISSUE-SPECIFIC EPIGENETIC SIGNATURES AND THEIR ROLE IN THE DEVELOPMENT OF CHRONIC DISEASES. FURTHER STUDIES SHOULD APPLY METHODS BASED ON GLOBAL ANALYSIS OF THE GENOME TO IDENTIFY METHYLATED SITES ASSOCIATED WITH DISEASE AND EPIGENETIC MARKS ASSOCIATED WITH THE REMODELING RESPONSE TO BARIATRIC SURGERY. THIS REVIEW DESCRIBES THE MAIN EPIGENETIC ALTERATIONS ASSOCIATED WITH OBESITY AND T2D AND THE POTENTIAL ROLE OF RYGB IN REMODELING THESE CHANGES. 2017 2 2789 43 FACTORS INFLUENCING EPIGENETIC MECHANISMS: IS THERE A ROLE FOR BARIATRIC SURGERY? EPIGENETICS IS THE INTERACTION BETWEEN THE GENOME AND ENVIRONMENTAL STIMULI CAPABLE OF INFLUENCING GENE EXPRESSION DURING DEVELOPMENT AND AGING. A LARGE NUMBER OF STUDIES HAVE SHOWN THAT METABOLIC DISEASES ARE HIGHLY ASSOCIATED WITH EPIGENETIC ALTERATIONS, SUGGESTING THAT EPIGENETIC FACTORS MAY PLAY A CENTRAL ROLE IN OBESITY. TO INVESTIGATE THESE RELATIONSHIPS, WE FOCUS OUR ATTENTION ON THE MOST COMMON EPIGENETIC MODIFICATIONS THAT OCCUR IN OBESITY, INCLUDING DNA METHYLATION AND POST-TRANSLATIONAL MODIFICATIONS OF HISTONES. WE ALSO CONSIDER BARIATRIC SURGERY AS AN EPIGENETIC FACTOR, EVALUATING HOW THE ANATOMIC AND PHYSIOLOGIC MODIFICATIONS INDUCED BY THESE SURGICAL TECHNIQUES CAN CHANGE GENE EXPRESSION. HERE WE DISCUSS THE IMPORTANCE OF EPIGENETIC MECHANISMS IN CHRONIC DISEASE AND CANCER, AND THE ROLE OF EPIGENETIC DISTURBANCES IN OBESITY, WITH A FOCUS ON THE ROLE OF BARIATRIC SURGERY. 2020 3 6462 55 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 4 2507 41 EPIGENETICS AND OBESITY: THE DEVIL IS IN THE DETAILS. OBESITY IS A COMPLEX DISEASE WITH MULTIPLE WELL-DEFINED RISK FACTORS. NEVERTHELESS, SUSCEPTIBILITY TO OBESITY AND ITS SEQUELAE WITHIN OBESOGENIC ENVIRONMENTS VARIES GREATLY FROM ONE PERSON TO THE NEXT, SUGGESTING A ROLE FOR GENE X ENVIRONMENT INTERACTIONS IN THE ETIOLOGY OF THE DISORDER. EPIGENETIC REGULATION OF THE HUMAN GENOME PROVIDES A PUTATIVE MECHANISM BY WHICH SPECIFIC ENVIRONMENTAL EXPOSURES CONVEY RISK FOR OBESITY AND OTHER HUMAN DISEASES AND IS ONE POSSIBLE MECHANISM THAT UNDERLIES THE GENE X ENVIRONMENT/TREATMENT INTERACTIONS OBSERVED IN EPIDEMIOLOGICAL STUDIES AND CLINICAL TRIALS. A STUDY PUBLISHED IN BMC MEDICINE THIS MONTH BY WANG ET AL. REPORTS ON AN EXAMINATION OF DNA METHYLATION IN PERIPHERAL BLOOD LEUKOCYTES OF LEAN AND OBESE ADOLESCENTS, COMPARING METHYLATION PATTERNS BETWEEN THE TWO GROUPS. THE AUTHORS IDENTIFIED TWO GENES THAT WERE DIFFERENTIALLY METHYLATED, BOTH OF WHICH HAVE ROLES IN IMMUNE FUNCTION. HERE WE OVERVIEW THE FINDINGS FROM THIS STUDY IN THE CONTEXT OF THOSE EMERGING FROM OTHER RECENT GENETIC AND EPIGENETIC STUDIES, DISCUSS THE STRENGTHS AND WEAKNESSES OF THE STUDY AND SPECULATE ON THE FUTURE OF EPIGENETICS IN CHRONIC DISEASE RESEARCH. 2010 5 1844 49 EFFECTS OF THE LIFESTYLE HABITS IN BREAST CANCER TRANSCRIPTIONAL REGULATION. THROUGH RESEARCH CARRIED OUT IN THE LAST 25 YEARS ABOUT THE BREAST CANCER ETIOLOGY, IT HAS BEEN POSSIBLE TO ESTIMATE THAT LESS THAN 10 % OF PATIENTS WHO ARE DIAGNOSED WITH THE CONDITION ARE CARRIERS OF SOME GERMLINE OR SOMATIC MUTATION. THE CLINICAL REPORTS OF BREAST CANCER PATIENTS WITH HEALTHY TWINS AND THE DEVELOPMENT OF DISEASE IN WOMEN WITHOUT HIGH PENETRANCE MUTATIONS DETECTED, WARN THE PARTICIPATION MORE FACTORS IN THE TRANSFORMATION PROCESS. THE HIGH INCIDENCE OF MAMMARY ADENOCARCINOMA IN THE MODERN WOMAN AND THE URGENT NEED FOR NEW METHODS OF PREVENTION AND EARLY DETECTION HAVE DEMANDED MORE INFORMATION ABOUT THE ROLE THAT ENVIRONMENT AND LIFESTYLE HAVE ON THE TRANSFORMATION OF MAMMARY GLAND EPITHELIAL CELLS. OBESITY, ALCOHOLISM AND SMOKING ARE FACTORS THAT HAVE SHOWN A CLOSE CORRELATION WITH THE RISK OF DEVELOPING BREAST CANCER. AND ALTHOUGH THESE CONDITIONS AFFECT DIFFERENT CELL REGULATION LEVELS, THE STUDY OF ITS EFFECTS IN THE MECHANISMS OF TRANSCRIPTIONAL AND EPIGENETIC REGULATION IS CONSIDERED CRITICAL FOR A BETTER UNDERSTANDING OF THE LOSS OF IDENTITY OF EPITHELIAL CELLS DURING CARCINOGENESIS OF THIS TISSUE. THE MAIN OBJECTIVE OF THIS REVIEW WAS TO ESTABLISH THE IMPORTANCE OF CHANGES OCCURRING TO TRANSCRIPTIONAL LEVEL IN THE MAMMARY GLAND AS A CONSEQUENCE OF ACUTE OR CHRONIC EXPOSURE TO HARMFUL PRODUCTS SUCH AS OBESITY-CAUSING FOODS, ETHANOL AND CIGARETTE SMOKE COMPONENTS. AT ANALYZE THE MAIN STUDIES RELATED TO TOPIC, IT HAS CONCLUDED THAT THE UNDERSTANDING OF EFFECTS CAUSED BY THE LIFESTYLE FACTORS IN PERFORMANCE OF THE TRANSCRIPTIONAL MECHANISMS THAT DETERMINE GENE EXPRESSION OF THE MAMMARY GLAND EPITHELIAL CELLS, MAY HELP EXPLAIN THE DEVELOPMENT OF THIS DISEASE IN WOMEN WITHOUT GENETIC PROPENSITY AND DIFFERENT PHENOTYPIC MANIFESTATIONS OF THIS CANCER TYPE. 2016 6 3848 41 IS EPIGENETICS AN IMPORTANT LINK BETWEEN EARLY LIFE EVENTS AND ADULT DISEASE? BACKGROUND: EPIGENETIC MECHANISMS PROVIDE ONE POTENTIAL EXPLANATION FOR HOW ENVIRONMENTAL INFLUENCES IN EARLY LIFE CAUSE LONG-TERM CHANGES IN CHRONIC DISEASE SUSCEPTIBILITY. WHEREAS EPIGENETIC DYSREGULATION IS INCREASINGLY IMPLICATED IN VARIOUS RARE DEVELOPMENTAL SYNDROMES AND CANCER, THE ROLE OF EPIGENETICS IN COMPLEX CHRONIC DISEASES, SUCH AS CARDIOVASCULAR DISEASE, TYPE 2 DIABETES AND OBESITY, REMAINS LARGELY UNCHARACTERIZED. EXTENSIVE WORK IN ANIMAL MODELS IS REQUIRED TO DEVELOP SPECIFIC HYPOTHESES THAT CAN BE PRACTICABLY TESTED IN HUMANS. ANIMAL MODELS: WE HAVE DEVELOPED A MOUSE MODEL SHOWING THAT METHYL DONOR SUPPLEMENTATION PREVENTS TRANSGENERATIONAL AMPLIFICATION OF OBESITY, SUGGESTING A ROLE FOR DNA METHYLATION IN THE DEVELOPMENTAL ESTABLISHMENT OF BODY WEIGHT REGULATION. CONCLUSIONS: COUPLING SUCH MODELS WITH RECENTLY DEVELOPED EPIGENOMIC TECHNOLOGIES SHOULD ULTIMATELY ENABLE US TO DETERMINE IF EPIGENETICS IS AN IMPORTANT LINK BETWEEN EARLY LIFE EVENTS AND ADULT DISEASE. 2009 7 4793 43 NUTRITIONAL FACTORS, DNA METHYLATION, AND RISK OF TYPE 2 DIABETES AND OBESITY: PERSPECTIVES AND CHALLENGES. A HEALTHY DIET IMPROVES LIFE EXPECTANCY AND HELPS TO PREVENT COMMON CHRONIC DISEASES SUCH AS TYPE 2 DIABETES (T2D) AND OBESITY. THE MECHANISMS DRIVING THESE EFFECTS ARE NOT FULLY UNDERSTOOD, BUT ARE LIKELY TO INVOLVE EPIGENETICS. EPIGENETIC MECHANISMS CONTROL GENE EXPRESSION, MAINTAINING THE DNA SEQUENCE, AND THEREFORE THE FULL GENOMIC INFORMATION INHERITED FROM OUR PARENTS, UNCHANGED. AN INTERESTING FEATURE OF EPIGENETIC CHANGES LIES IN THEIR DYNAMIC NATURE AND REVERSIBILITY. ACCORDINGLY, THEY ARE SUSCEPTIBLE TO CORRECTION THROUGH TARGETED INTERVENTIONS. HERE WE WILL REVIEW THE EVIDENCE SUPPORTING A ROLE FOR NUTRITIONAL FACTORS IN MEDIATING METABOLIC DISEASE RISK THROUGH DNA METHYLATION CHANGES. SPECIAL EMPHASIS WILL BE PLACED ON THE POTENTIAL OF USING DNA METHYLATION TRAITS AS BIOMARKERS TO PREDICT RISK OF OBESITY AND T2D AS WELL AS ON THEIR RESPONSE TO DIETARY AND PHARMACOLOGICAL (EPI-DRUG) INTERVENTIONS. 2019 8 3915 42 LINE-1 IN OBESITY AND CARDIOMETABOLIC DISEASES: A SYSTEMATIC REVIEW. EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF OBESITY AND CARDIOMETABOLIC DISEASES, BY ACTIVATING OR SILENCING THE RELATED-GENES. SCIENTIFIC EVIDENCE HAS SUGGESTED THAT LINE-1 METHYLATION IS ASSOCIATED WITH BODY COMPOSITION AND OBESITY-RELATED DISEASES, INCLUDING INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE (CVD). IT ALSO HAS BEEN EVALUATED AS PREDICTOR OF WEIGHT LOSS. THE STUDIES' RESULTS ARE STILL CONFLICTING, AND POSITIVE AND NEGATIVE ASSOCIATIONS HAVE BEEN FOUND TO LINE-1 METHYLATION REGARDING ADIPOSITY AND CARDIOMETABOLIC MARKERS. OVERALL, THIS REVIEW PRESENTS OBSERVATIONAL (CROSS-SECTIONAL AND LONGITUDINAL) STUDIES AND INTERVENTIONS (DIET, EXERCISES, AND BARIATRIC SURGERY) THAT EVALUATED THE RELATIONSHIP OF THE LINE-1 METHYLATION WITH OBESITY, WEIGHT LOSS, DYSLIPIDEMIAS, HYPERTENSION, INSULIN RESISTANCE, CVD, AND METABOLIC SYNDROME. TEACHING POINTS EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF OBESITY AND CARDIOMETABOLIC DISEASES. MANY STUDIES HAVE RELATED METHYLATION OF LINE-1 WITH CARDIOMETABOLIC DISEASES; HOWEVER, THE RESULTS ARE STILL CONTROVERSIAL. THE RELATIONSHIP BETWEEN THE ETIOLOGY OF CHRONIC DISEASES AND THE METHYLATION OF LINE-1 IS NOT FULLY ELUCIDATED. WITH ADVANCES IN EPIGENETIC STUDIES, RELATED MECHANISMS MAY BE EARLY BIOMARKERS IN WEIGHT CHANGE AND CARDIOMETABOLIC RISK. 2019 9 6812 40 [EPIGENETICS, INTERFACE BETWEEN ENVIRONMENT AND GENES: ROLE IN COMPLEX DISEASES]. EPIGENETICS IS THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION OR CELLULAR PHENOTYPE CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE. EPIGENETICS IS ONE OF THE MAJOR MECHANISMS EXPLAINING THE "DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASES" (DOHAD). BESIDES GENETIC BACKGROUND INHERITED FROM PARENTS, WHICH CONFERS SUSCEPTIBILITY TO CERTAIN PATHOLOGIES, EPIGENETIC CHANGES CONSTITUTE THE MEMORY OF PREVIOUS EVENTS, EITHER POSITIVE OR NEGATIVE, ALONG THE LIFE CYCLE, INCLUDING AT THE IN UTERO STAGE. THE LATER EXPOSITION TO HOSTILE ENVIRONMENT MAY REVEAL SUCH SUSCEPTIBILITY, WITH THE DEVELOPMENT OF VARIOUS PATHOLOGIES, AMONG THEM NUMEROUS CHRONIC COMPLEX DISEASES. THE DEMONSTRATION OF SUCH A SEQUENCE OF EVENTS HAS BEEN SHOWN FOR METABOLIC DISEASES AS OBESITY, METABOLIC SYNDROME AND TYPE 2 DIABETES, CARDIOVASCULAR DISEASE AND CANCER. IN CONTRAST TO GENETIC PREDISPOSITION, WHICH IS IRREVERSIBLE, EPIGENETIC CHANGES ARE POTENTIALLY REVERSIBLE, THUS GIVING TARGETS NOT ONLY FOR PREVENTION, BUT POSSIBLY ALSO FOR THE TREATMENT OF CERTAIN COMPLEX DISEASES. 2012 10 6809 35 [EPIGENETICS IN INFLAMMATORY SYSTEMIC DISEASES]. IN ADDITION TO ANALYSIS OF THE GENETIC CODE, IN RECENT YEARS MORE AND MORE STUDIES HAVE CONCENTRATED ON CHANGES IN THE EPIGENETIC CODE. EPIGENETIC MECHANISMS DETERMINE WHICH GENES IN A CELL ARE TRANSCRIBED AND THUS FORM THE PHENOTYPE OF A CELL. THE EPIGENETIC CODE CAN BE CHANGED BY ENVIRONMENTAL INFLUENCES, WHICH ALLOWS CELLS TO ADAPT TO LONGSTANDING CHANGES IN THE ENVIRONMENT. THEREFORE, IT IS FEASIBLE TO ASSUME THAT EPIGENETIC CHANGES ARE THE MOLECULAR BASIS FOR LONG-TERM EFFECTS OF THE ENVIRONMENT ON DISEASE DEVELOPMENT. IN PARTICULAR IN TUMORS AND CHRONIC INFLAMMATORY DISEASES EPIGENETIC CHANGES WERE FOUND TO CORRELATE WITH DISEASE SEVERITY AND PROGRESSION. KNOWLEDGE ABOUT THESE EPIGENETIC CHANGES MIGHT HELP THAT EPIGENETIC MODIFICATIONS CAN BE USED IN THE FUTURE AS BIOMARKERS, PROGNOSTIC FACTORS AND THERAPEUTIC TARGETS. 2014 11 4972 40 PATHOPHYSIOLOGICAL BASIS FOR COMPROMISED HEALTH BEYOND GENERATIONS: ROLE OF MATERNAL HIGH-FAT DIET AND LOW-GRADE CHRONIC INFLAMMATION. EARLY EXPOSURE TO A FAT-ENRICHED DIET PROGRAMS THE DEVELOPMENTAL PROFILE AND THUS IS ASSOCIATED WITH DISEASE SUSCEPTIBILITY IN SUBSEQUENT GENERATIONS. CHRONIC LOW-GRADE INFLAMMATION, RESULTING FROM MATERNAL HIGH-FAT DIET, IS ACTIVATED IN THE FETAL ENVIRONMENT AND IN MANY ORGANS OF OFFSPRING, INCLUDING PLACENTA, ADIPOSE, LIVER, VASCULAR SYSTEM AND BRAIN. THE PREVALENCE OF AN INFLAMMATORY RESPONSE IS HIGHLY ASSOCIATED WITH OBESITY INCIDENCE, CARDIOVASCULAR DISEASES, NONALCOHOLIC FATTY LIVER DISEASE AND BRAIN DAMAGE. SUBSTANTIAL STUDIES USING HIGH-FAT MODEL HAVE CONSISTENTLY DEMONSTRATED THE INCIDENCE OF SUCH INFLAMMATORY REACTIONS; HOWEVER, THE POTENTIAL CONTRIBUTION OF ACTIVE INFLAMMATION TOWARD THE PHYSIOLOGICAL OUTCOMES AND DEVELOPMENTAL DISEASES IS NEITHER DISCUSSED IN DEPTH NOR SYSTEMICALLY INTEGRATED. THEREFORE, WE AIM TO SUMMARIZE THE CURRENT FINDINGS IN REGARDS TO HOW A MATERNAL HIGH-FAT DIET INFLUENCES THE INFLAMMATORY STATUS, AND PROBABLE PATHOGENIC EFFECTS ON THE OFFSPRING. MORE IMPORTANTLY, SINCE LIMITED RESEARCH HAS BEEN CONDUCTED TO REVEAL THE EPIGENETIC REGULATION OF THESE INFLAMMATORY MARKERS BY MATERNAL HIGH-FAT DIET, WE SINCERELY HOPE THAT OUR REVIEW WILL NOT ONLY OUTLINE THE PATHOPHYSIOLOGICAL RELEVANCE OF INFLAMMATION BUT ALSO IDENTIFY A FUTURE DIRECTION FOR MECHANISTIC INVESTIGATION AND CLINICAL APPLICATION. 2015 12 396 42 AN UPDATE ON EPIGENETICS AND CHILDHOOD RESPIRATORY DISEASES. EPIGENETIC MECHANISMS, DEFINED AS CHANGES IN PHENOTYPE OR GENE EXPRESSION CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE, HAVE BEEN PROPOSED TO CONSTITUTE A LINK BETWEEN GENETIC AND ENVIRONMENTAL FACTORS THAT AFFECT COMPLEX DISEASES. RECENT STUDIES SHOW THAT DNA METHYLATION, ONE OF THE KEY EPIGENETIC MECHANISMS, IS ALTERED IN CHILDREN EXPOSED TO AIR POLLUTANTS AND ENVIRONMENTAL TOBACCO SMOKE EARLY IN LIFE. SEVERAL CANDIDATE GENE STUDIES ON EPIGENETICS HAVE BEEN PUBLISHED TO DATE, BUT IT IS ONLY RECENTLY THAT GLOBAL METHYLATION ANALYSES HAVE BEEN PERFORMED FOR RESPIRATORY DISORDERS SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HOWEVER, LARGE-SCALE STUDIES WITH ADEQUATE POWER ARE YET TO BE PRESENTED IN CHILDREN, AND IMPLICATIONS FOR CLINICAL USE REMAIN TO BE EVALUATED. IN THIS REVIEW, WE SUMMARIZE THE RECENT ADVANCES IN EPIGENETICS AND RESPIRATORY DISORDERS IN CHILDREN, WITH A MAIN FOCUS ON METHODOLOGICAL CHALLENGES AND ANALYSES RELATED TO PHENOTYPE AND EXPOSURE USING GLOBAL METHYLATION APPROACHES. 2014 13 2651 47 EPIGENOMICS AND TRANSCRIPTOMICS IN THE PREDICTION AND DIAGNOSIS OF CHILDHOOD ASTHMA: ARE WE THERE YET? ASTHMA IS THE MOST COMMON NON-COMMUNICABLE CHRONIC DISEASE OF CHILDHOOD. DESPITE ITS HIGH PREVALENCE, TO DATE WE LACK METHODS THAT ARE BOTH EFFICIENT AND ACCURATE IN DIAGNOSING ASTHMA. MOST TRADITIONAL APPROACHES HAVE BEEN BASED ON GARNERING CLINICAL EVIDENCE, SUCH AS RISK FACTORS AND EXPOSURES. GIVEN THE HIGH HERITABILITY OF ASTHMA, MORE RECENT APPROACHES HAVE LOOKED AT GENETIC POLYMORPHISMS AS POTENTIAL "RISK FACTORS." HOWEVER, GENETIC VARIANTS EXPLAIN ONLY A SMALL PROPORTION OF ASTHMA RISK, AND HAVE BEEN LESS THAN OPTIMAL AT PREDICTING RISK FOR INDIVIDUAL SUBJECTS. EPIGENOMIC STUDIES OFFER SIGNIFICANT ADVANTAGES OVER PREVIOUS APPROACHES. EPIGENETIC REGULATION IS HIGHLY TISSUE-SPECIFIC, AND CAN INDUCE BOTH SHORT- AND LONG-TERM CHANGES IN GENE EXPRESSION. SUCH CHANGES CAN START IN UTERO, CAN VARY THROUGHOUT THE LIFE SPAN, AND IN SOME INSTANCES CAN BE PASSED ON FROM ONE GENERATION TO ANOTHER. MOST IMPORTANTLY, THE EPIGENOME CAN BE MODIFIED BY ENVIRONMENTAL FACTORS AND EXPOSURES, AND THUS EPIGENETIC AND TRANSCRIPTOMIC PROFILING MAY YIELD THE MOST ACCURATE RISK ESTIMATES FOR A GIVEN PATIENT BY INCORPORATING ENVIRONMENTAL (AND TREATMENT) EFFECTS THROUGHOUT THE LIFESPAN. HERE WE WILL REVIEW THE MOST RECENT ADVANCES IN THE USE OF EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS FOR THE EARLY DIAGNOSIS OF ASTHMA AND ATOPY, AS WELL AS CHALLENGES AND FUTURE DIRECTIONS IN THE FIELD AS IT MOVES FORWARD. WE WILL PARTICULARLY FOCUS ON DNA METHYLATION, THE MOST STUDIED MECHANISM OF EPIGENETIC REGULATION. 2019 14 738 34 CANCER SUSCEPTIBILITY: EPIGENETIC MANIFESTATION OF ENVIRONMENTAL EXPOSURES. CANCER IS A DISEASE THAT RESULTS FROM BOTH GENETIC AND EPIGENETIC CHANGES. DISCORDANT PHENOTYPES AND VARYING INCIDENCES OF COMPLEX DISEASES SUCH AS CANCER IN MONOZYGOTIC TWINS AS WELL AS GENETICALLY IDENTICAL LABORATORY ANIMALS HAVE LONG BEEN ATTRIBUTED TO DIFFERENCES IN ENVIRONMENTAL EXPOSURES. ACCUMULATING EVIDENCE INDICATES, HOWEVER, THAT DISPARITIES IN GENE EXPRESSION RESULTING FROM VARIABLE MODIFICATIONS IN DNA METHYLATION AND CHROMATIN STRUCTURE IN RESPONSE TO THE ENVIRONMENT ALSO PLAY A ROLE IN DIFFERENTIAL SUSCEPTIBILITY TO DISEASE. DESPITE A GROWING CONSENSUS ON THE IMPORTANCE OF EPIGENETICS IN THE ETIOLOGY OF CHRONIC HUMAN DISEASES, THE GENES MOST PRONE TO EPIGENETIC DYSREGULATION ARE INCOMPLETELY DEFINED. MOREOVER, NEITHER THE ENVIRONMENTAL AGENTS MOST STRONGLY AFFECTING THE EPIGENOME NOR THE CRITICAL WINDOWS OF VULNERABILITY TO ENVIRONMENTALLY INDUCED EPIGENETIC ALTERATIONS ARE ADEQUATELY CHARACTERIZED. THESE MAJOR DEFICITS IN KNOWLEDGE MARKEDLY IMPAIR OUR ABILITY TO UNDERSTAND FULLY THE ETIOLOGY OF CANCER AND THE IMPORTANCE OF THE EPIGENOME IN DIAGNOSING AND PREVENTING THIS DEVASTATING DISEASE. 2007 15 4192 32 METABOLIC MEMORY AND CHRONIC DIABETES COMPLICATIONS: POTENTIAL ROLE FOR EPIGENETIC MECHANISMS. RECENT ESTIMATES INDICATE THAT DIABETES MELLITUS CURRENTLY AFFECTS MORE THAN 10 % OF THE WORLD'S POPULATION. EVIDENCE FROM BOTH THE LABORATORY AND LARGE SCALE CLINICAL TRIALS HAS REVEALED THAT PROLONGED HYPERGLYCEMIA INDUCES CHRONIC COMPLICATIONS WHICH PERSIST AND PROGRESS UNIMPEDED EVEN WHEN GLYCEMIC CONTROL IS PHARMACEUTICALLY ACHIEVED VIA THE PHENOMENON OF METABOLIC MEMORY. THE EPIGENOME IS COMPRISED OF ALL CHROMATIN MODIFICATIONS INCLUDING POST TRANSLATIONAL HISTONE MODIFICATION, EXPRESSION CONTROL VIA MIRNAS AND THE METHYLATION OF CYTOSINE WITHIN DNA. MODIFICATIONS OF THESE EPIGENETIC MARKS NOT ONLY ALLOW CELLS AND ORGANISMS TO QUICKLY RESPOND TO CHANGING ENVIRONMENTAL STIMULI BUT ALSO CONFER THE ABILITY OF THE CELL TO "MEMORIZE" THESE ENCOUNTERS. AS SUCH, THESE PROCESSES HAVE GAINED MUCH ATTENTION AS POTENTIAL MOLECULAR MECHANISMS UNDERLYING METABOLIC MEMORY AND CHRONIC DIABETIC COMPLICATIONS. HERE WE PRESENT A REVIEW OF THE VERY RECENT LITERATURE PUBLISHED PERTAINING TO THIS SUBJECT. 2012 16 6199 46 THE IMPORTANCE OF EPIGENETICS IN THE DEVELOPMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT IS GENERALLY ACCEPTED THAT GENETIC PREDISPOSITION PLAYS A ROLE IN COPD DEVELOPMENT IN SUSCEPTIBLE INDIVIDUALS. THEREFORE, MANY CANDIDATE GENES THAT COULD BE LINKED TO THE DEVELOPMENT OF DISEASE HAVE BEEN EXAMINED IN COPD. HOWEVER, INCONSISTENT RESULTS IN DIFFERENT STUDY POPULATIONS OFTEN LIMIT THIS APPROACH, SUGGESTING THAT NOT ONLY GENETICS, BUT ALSO OTHER FACTORS, MAY BE CONTRIBUTED TO THE SUSCEPTIBILITY TO COPD. EPIGENETIC MECHANISMS CAN AFFECT THE TRANSCRIPTIONAL ACTIVITY OF SPECIFIC GENES, AT DIFFERENT POINTS IN TIME, AND IN DIFFERENT ORGANS. MOREOVER, THESE MECHANISMS CAN HAVE AN EFFECT ON PEOPLE'S HEALTH. RECENTLY, THERE IS EMERGING EVIDENCE SUPPORTING A ROLE OF EPIGENETICS FOR THE REGULATION OF INFLAMMATORY GENES IN DISEASES SUCH AS ASTHMA AND COPD. MOREOVER, RECENT STUDIES SUGGEST THAT THE CURRENTLY USED TREATMENTS INCLUDING CORTICOSTEROIDS MAY WORK THROUGH EPIGENETIC MECHANISMS. EPIGENETIC REGULATION CAN BE REPROGRAMMED, POTENTIALLY AFFECTING THE RISK, AETIOLOGY AND TREATMENT OF VARIOUS DISEASE STATES. THE EPIGENETICALLY INFLUENCED PHENOTYPE COULD BE REVERSED WITH DEMETHYLATING OR DEACETYLATING AGENTS, CONSISTENT WITH EPIGENETIC PLASTICITY. THE POSTNATAL REVERSIBILITY OF THESE METHYLATION OR ACETYLATION EVENTS MAY THEREFORE PROVIDE GOOD OPPORTUNITIES FOR INTERVENTION. THE RECOGNITION OF THE ROLE OF GENETIC AND EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF COPD MAY IDENTIFY NOVEL TARGETS THAT HATCH NEW THERAPIES FOR PATIENTS WITH COPD. 2011 17 4425 49 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 18 776 47 CELL- AND TISSUE-SPECIFIC EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC INFLAMMATION IN INSULIN RESISTANCE AND TYPE 2 DIABETES MELLITUS. TYPE 2 DIABETES MELLITUS (T2DM) IS A CHRONIC METABOLIC DISORDER CHARACTERIZED BY HYPERGLYCAEMIA, WHICH CAN CAUSE MICRO- AND MACROVASCULAR COMPLICATIONS. CHRONIC INFLAMMATION MAY BE THE CAUSE AND RESULT OF T2DM, AND ITS RELATED COMPLICATIONS AS AN IMBALANCE BETWEEN PRO- AND ANTI-INFLAMMATORY CYTOKINES CAN AFFECT IMMUNE FUNCTIONS. APART FROM GENETIC CHANGES OCCURRING WITHIN THE BODY RESULTING IN INFLAMMATION IN T2DM, EPIGENETIC MODIFICATIONS CAN MODIFY GENE EXPRESSION IN RESPONSE TO ENVIRONMENTAL CUES SUCH AS AN UNHEALTHY DIET, LACK OF EXERCISE AND OBESITY. THE MOST WIDELY STUDIED EPIGENETIC MODIFICATION, DNA METHYLATION (DNAM), REGULATES GENE EXPRESSION AND MAY MANIPULATE INFLAMMATORY GENES TO INCREASE OR DECREASE INFLAMMATION ASSOCIATED WITH T2DM. THIS REVIEW EXPLORES THE STUDIES RELATED TO EPIGENETIC CHANGES, MORE SPECIFICALLY DNAM, ASSOCIATED WITH CHRONIC INFLAMMATION IN T2DM, AT BOTH THE CELL AND TISSUE LEVELS. STUDYING EPIGENETIC ALTERATIONS DURING INFLAMMATORY RESPONSE, AS A RESULT OF GENETIC AND ENVIRONMENTAL SIGNALS, CREATES OPPORTUNITIES FOR THE DEVELOPMENT OF "EARLY DETECTION/RELATIVE RISK" TESTS TO AID IN PREVENTION OF T2DM. UNDERSTANDING INFLAMMATION IN T2DM AT THE GENE LEVEL IN INFLAMMATION-ASSOCIATED CELLS AND TISSUES MAY PROVIDE FURTHER INSIGHT FOR THE DEVELOPMENT OF SPECIFIC THERAPEUTIC TARGETS FOR THE DISORDER. 2018 19 4787 39 NUTRITION, AGING AND CANCER: LESSONS FROM DIETARY INTERVENTION STUDIES. THERE IS CONVINCING EPIDEMIOLOGICAL AND CLINICAL EVIDENCE THAT, INDEPENDENT OF AGING, LIFESTYLE AND, NOTABLY, NUTRITION ARE ASSOCIATED WITH DEVELOPMENT OR PROGRESSION OF MAJOR HUMAN CANCERS, INCLUDING BREAST, PROSTATE, COLORECTAL TUMORS, AND AN INCREASINGLY LARGE COLLECTION OF DIET-RELATED CANCERS. MECHANISMS UNDERLYING THIS ASSOCIATION ARE MOSTLY RELATED TO THE DISTINCT EPIGENETIC EFFECTS OF DIFFERENT DIETARY PATTERNS. IN THIS CONTEXT, MEDITERRANEAN DIET HAS BEEN REPORTED TO SIGNIFICANTLY REDUCE MORTALITY RATES FOR VARIOUS CHRONIC ILLNESSES, INCLUDING CARDIOVASCULAR DISEASES, NEURODEGENERATIVE DISEASES AND CANCER. ALTHOUGH MANY OBSERVATIONAL STUDIES HAVE SUPPORTED THIS EVIDENCE, DIETARY INTERVENTION STUDIES USING A MEDITERRANEAN DIETARY PATTERN OR ITS SELECTED FOOD COMPONENTS ARE STILL LIMITED AND AFFECTED BY A RATHER LARGE VARIABILITY IN CHARACTERISTICS OF STUDY SUBJECTS, TYPE AND LENGTH OF INTERVENTION, SELECTED END-POINTS AND STATISTICAL ANALYSIS. HERE WE REVIEW DATA OF TWO OF OUR INTERVENTION STUDIES, THE MEDIET STUDY AND THE DIMESA PROJECT, AIMED AT ASSESSING THE EFFECTS OF TRADITIONAL MEDITERRANEAN DIET AND/OR ITS COMPONENT(S) ON A LARGE PANEL OF BOTH PLASMA AND URINE BIOMARKERS. BOTH PUBLISHED AND UNPUBLISHED RESULTS ARE PRESENTED AND DISCUSSED. 2016 20 6380 40 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