1 3882 102 KETONE BODIES AS METABOLITES AND SIGNALLING MOLECULES AT THE CROSSROAD BETWEEN INFLAMMATION AND EPIGENETIC CONTROL OF CARDIOMETABOLIC DISORDERS. FOR MANY YEARS, IT HAS BEEN CLEAR THAT A WESTERN DIET RICH IN SATURATED FATS AND SUGARS PROMOTES AN INFLAMMATORY ENVIRONMENT PREDISPOSING A PERSON TO CHRONIC CARDIOMETABOLIC DISEASES. IN PARALLEL, THE EMERGENCE OF KETOGENIC DIETS, DEPRIVED OF CARBOHYDRATES AND PROMOTING THE SYNTHESIS OF KETONE BODIES IMITATING THE METABOLIC EFFECTS OF FASTING, HAS BEEN SHOWN TO PROVIDE A POSSIBLE NUTRITIONAL SOLUTION TO ALLEVIATING DISEASES TRIGGERED BY AN INFLAMMATORY ENVIRONMENT. THE MAIN KETONE BODY, BETA-HYDROXYBUTYRATE (BHB), ACTS AS AN ALTERNATIVE FUEL, AND ALSO AS A SUBSTRATE FOR A NOVEL HISTONE POST-TRANSLATIONAL MODIFICATION, BETA-HYDROXYBUTYRYLATION. BETA-HYDROXYBUTYRYLATION INFLUENCES THE STATE OF CHROMATIN ARCHITECTURE AND PROMOTES THE TRANSCRIPTION OF MULTIPLE GENES. BHB HAS ALSO BEEN SHOWN TO MODULATE INFLAMMATION IN CHRONIC DISEASES. IN THIS REVIEW, WE DISCUSS, IN THE PATHOLOGICAL CONTEXT OF CARDIOVASCULAR RISKS, THE CURRENT UNDERSTANDING OF HOW KETONE BODIES, OR A KETOGENIC DIET, ARE ABLE TO MODULATE, TRIGGER, OR INHIBIT INFLAMMATION AND HOW THE EPIGENOME AND CHROMATIN REMODELING MAY BE A KEY CONTRIBUTOR. 2022 2 2562 25 EPIGENETICS IN THE PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE: INFLUENCE OF EXERCISE AND NUTRITION. INCREASING EVIDENCE LINKS CHANGES IN EPIGENETIC SYSTEMS, SUCH AS DNA METHYLATION, HISTONE MODIFICATION, AND NON-CODING RNA EXPRESSION, TO THE OCCURRENCE OF CARDIOVASCULAR DISEASE (CVD). THESE EPIGENETIC MODIFICATIONS CAN CHANGE GENETIC FUNCTION UNDER INFLUENCE OF EXOGENOUS STIMULI AND CAN BE TRANSFERRED TO NEXT GENERATIONS, PROVIDING A POTENTIAL MECHANISM FOR INHERITANCE OF BEHAVIOURAL INTERVENTION EFFECTS. THE BENEFITS OF EXERCISE AND NUTRITIONAL INTERVENTIONS IN THE PRIMARY AND SECONDARY PREVENTION OF CVD ARE WELL ESTABLISHED, BUT THE MECHANISMS ARE NOT COMPLETELY UNDERSTOOD. IN THIS REVIEW, WE DESCRIBE THE ACUTE AND CHRONIC EPIGENETIC EFFECTS OF PHYSICAL ACTIVITY AND DIETARY CHANGES. WE PROPOSE EXERCISE AND NUTRITION AS POTENTIAL TRIGGERS OF EPIGENETIC SIGNALS, PROMOTING THE RESHAPING OF TRANSCRIPTIONAL PROGRAMMES WITH EFFECTS ON CVD PHENOTYPES. FINALLY, WE HIGHLIGHT RECENT DEVELOPMENTS IN EPIGENETIC THERAPEUTICS WITH IMPLICATIONS FOR PRIMARY AND SECONDARY CVD PREVENTION. 2022 3 2577 27 EPIGENETICS OF INFLAMMATION, MATERNAL INFECTION, AND NUTRITION. STUDIES HAVE DEMONSTRATED THAT EPIGENETIC CHANGES SUCH AS DNA METHYLATION, HISTONE MODIFICATION, AND CHROMATIN REMODELING ARE LINKED TO AN INCREASED INFLAMMATORY RESPONSE AS WELL AS INCREASED RISK OF CHRONIC DISEASE DEVELOPMENT. A FEW STUDIES HAVE BEGUN TO INVESTIGATE WHETHER DIETARY NUTRIENTS PLAY A BENEFICIAL ROLE BY MODIFYING OR REVERSING EPIGENETICALLY INDUCED INFLAMMATION. RESULTS OF THESE STUDIES SHOW THAT NUTRIENTS MODIFY EPIGENETIC PATHWAYS. HOWEVER, LITTLE IS KNOWN ABOUT HOW NUTRIENTS MODULATE INFLAMMATION BY REGULATING IMMUNE CELL FUNCTION AND/OR IMMUNE CELL DIFFERENTIATION VIA EPIGENETIC PATHWAYS. THIS OVERVIEW WILL PROVIDE INFORMATION ABOUT THE CURRENT UNDERSTANDING OF THE ROLE OF NUTRIENTS IN THE EPIGENETIC CONTROL MECHANISMS OF IMMUNE FUNCTION. 2015 4 2360 24 EPIGENETIC REGULATION OF SKELETAL MUSCLE METABOLISM. NORMAL SKELETAL MUSCLE METABOLISM IS ESSENTIAL FOR WHOLE BODY METABOLIC HOMOEOSTASIS AND DISRUPTIONS IN MUSCLE METABOLISM ARE ASSOCIATED WITH A NUMBER OF CHRONIC DISEASES. TRANSCRIPTIONAL CONTROL OF METABOLIC ENZYME EXPRESSION IS A MAJOR REGULATORY MECHANISM FOR MUSCLE METABOLIC PROCESSES. SUBSTANTIAL EVIDENCE IS EMERGING THAT HIGHLIGHTS THE IMPORTANCE OF EPIGENETIC MECHANISMS IN THIS PROCESS. THIS REVIEW WILL EXAMINE THE IMPORTANCE OF EPIGENETICS IN THE REGULATION OF MUSCLE METABOLISM, WITH A PARTICULAR EMPHASIS ON DNA METHYLATION AND HISTONE ACETYLATION AS EPIGENETIC CONTROL POINTS. THE EMERGING CROSS-TALK BETWEEN METABOLISM AND EPIGENETICS IN THE CONTEXT OF HEALTH AND DISEASE WILL ALSO BE EXAMINED. THE CONCEPT OF INHERITANCE OF SKELETAL MUSCLE METABOLIC PHENOTYPES WILL BE DISCUSSED, IN ADDITION TO EMERGING EPIGENETIC THERAPIES THAT COULD BE USED TO ALTER MUSCLE METABOLISM IN CHRONIC DISEASE STATES. 2016 5 3593 30 IMPLICATION OF THE MEDITERRANEAN DIET ON THE HUMAN EPIGENOME. EPIGENETICS, DEFINED AS "HEREDITARY CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT ANY CHANGE IN THE DNA SEQUENCE", CONSISTS OF VARIOUS EPIGENETIC MARKS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNAS. THE EPIGENOME, WHICH HAS A DYNAMIC STRUCTURE IN RESPONSE TO INTRACELLULAR AND EXTRACELLULAR STIMULI, HAS A KEY ROLE IN THE CONTROL OF GENE ACTIVITY, SINCE IT IS LOCATED AT THE INTERSECTION OF CELLULAR INFORMATION ENCODED IN THE GENOME AND MOLECULAR/CHEMICAL INFORMATION OF EXTRACELLULAR ORIGIN. THE FOCUS SHIFT OF STUDIES TO EPIGENETIC REPROGRAMMING HAS LED TO THE FORMATION AND PROGRESSIVE IMPORTANCE OF A CONCEPT CALLED "NUTRIEPIGENETICS", WHOSE AIM IS TO PREVENT DISEASES BY INTERVENING ON NUTRITION STYLE. AMONG THE DIET TYPES ADOPTED IN THE WORLD, THE RENOWNED MEDITERRANEAN DIET (MD), BEING RICH IN UNSATURATED FATTY ACIDS AND CONTAINING HIGH LEVELS OF WHOLE GRAIN FOODS AND LARGE QUANTITIES OF FRUITS, VEGETABLES, AND LEGUMES, HAS SHOWN NUMEROUS ADVANTAGES IN EXCLUDING CHRONIC DISEASES. ADDITIONALLY, THE FACT THAT THIS DIET IS RICH IN POLYPHENOLS WITH HIGH ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES HAS AN UNDENIABLE EFFECT IN TURNING SOME CELLULAR PATHWAYS AGAINST THE DISEASE. IT IS ALSO APPARENT THAT THE EFFECTS OF POLYPHENOLS ON THE EPIGENOME CAUSE CHANGES IN MECHANISMS SUCH AS DNA METHYLATION AND HISTONE ACETYLATION/DEACETYLATION, WHICH HAVE A REGULATORY EFFECT ON GENE REGULATION. THIS REVIEW PRESENTS THE EFFECTS OF LONG-TERM CONSUMPTION OF NUTRIENTS FROM THE MD ON THE EPIGENOME AND DISCUSSES THE BENEFITS OF THIS DIET IN THE TREATMENT AND EVEN PREVENTION OF CHRONIC DISEASES. 2022 6 4273 27 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 7 5821 32 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 8 128 27 A UNIFYING MECHANISM OF KETOGENIC DIET ACTION: THE MULTIPLE ROLES OF NICOTINAMIDE ADENINE DINUCLEOTIDE. THE ABILITY OF A KETOGENIC DIET TO TREAT SEIZURES AND RENDER A NEURONAL NETWORK MORE RESISTANT TO STRONG ELECTRICAL ACTIVITY HAS BEEN OBSERVED FOR A CENTURY IN CLINICS AND FOR DECADES IN RESEARCH LABORATORIES. ALONGSIDE ONGOING EFFORTS TO UNDERSTAND HOW THIS THERAPY WORKS TO STOP SEIZURES, METABOLIC HEALTH IS INCREASINGLY APPRECIATED AS CRITICAL BUFFER TO RESISTING AND RECOVERING FROM ACUTE AND CHRONIC DISEASE. ACCORDINGLY, LINKS BETWEEN METABOLISM AND HEALTH, AND THE BROADER EMERGING IMPACT OF THE KETOGENIC DIET IN IMPROVING DIVERSE METABOLIC, IMMUNOLOGICAL AND NEUROLOGICAL CONDITIONS, HAVE SERVED TO INTENSIFY THE SEARCH FOR ITS KEY AND/OR COMMON MECHANISMS. HERE WE REVIEW DIVERSE EVIDENCE FOR INCREASED LEVELS OF NAD(+), AND THUS AN ALTERED RATIO OF NAD(+)/NADH, DURING METABOLIC THERAPY WITH A KETOGENIC DIET. WE PROPOSE THIS AS A POTENTIAL UNIFYING MECHANISM, AND HIGHLIGHT SOME OF THE EVIDENCE LINKING ALTERED NAD(+)/NADH WITH REDUCED SEIZURES AND WITH A RANGE OF SHORT AND LONG-TERM CHANGES ASSOCIATED WITH THE BENEFICIAL EFFECTS OF A KETOGENIC DIET. AN INCREASE IN NAD(+)/NADH IS CONSISTENT WITH MULTIPLE LINES OF EVIDENCE AND HYPOTHESES, AND THEREFORE WE SUGGEST THAT INCREASED NAD(+) MAY BE A COMMON MECHANISM UNDERLYING BENEFICIAL EFFECTS OF KETOGENIC DIET THERAPY. 2020 9 3547 39 IMMUNOMODULATORY ROLE OF NUTRIENTS: HOW CAN PULMONARY DYSFUNCTIONS IMPROVE? NUTRITION IS AN IMPORTANT TOOL THAT CAN BE USED TO MODULATE THE IMMUNE RESPONSE DURING INFECTIOUS DISEASES. IN ADDITION, THROUGH DIET, IMPORTANT SUBSTRATES ARE ACQUIRED FOR THE BIOSYNTHESIS OF REGULATORY MOLECULES IN THE IMMUNE RESPONSE, INFLUENCING THE PROGRESSION AND TREATMENT OF CHRONIC LUNG DISEASES, SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). IN THIS WAY, NUTRITION CAN PROMOTE LUNG HEALTH STATUS. A RANGE OF NUTRIENTS, SUCH AS VITAMINS (A, C, D, AND E), MINERALS (ZINC, SELENIUM, IRON, AND MAGNESIUM), FLAVONOIDS AND FATTY ACIDS, PLAY IMPORTANT ROLES IN REDUCING THE RISK OF PULMONARY CHRONIC DISEASES AND VIRAL INFECTIONS. THROUGH THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS, NUTRIENTS ARE ASSOCIATED WITH BETTER LUNG FUNCTION AND A LOWER RISK OF COMPLICATIONS SINCE THEY CAN DECREASE THE HARMFUL EFFECTS FROM THE IMMUNE SYSTEM DURING THE INFLAMMATORY RESPONSE. IN ADDITION, BIOACTIVE COMPOUNDS CAN EVEN CONTRIBUTE TO EPIGENETIC CHANGES, INCLUDING HISTONE DEACETYLASE (HDAC) MODIFICATIONS THAT INHIBIT THE TRANSCRIPTION OF PROINFLAMMATORY CYTOKINES, WHICH CAN CONTRIBUTE TO THE MAINTENANCE OF HOMEOSTASIS IN THE CONTEXT OF INFECTIONS AND CHRONIC INFLAMMATORY DISEASES. THESE NUTRIENTS ALSO PLAY AN IMPORTANT ROLE IN ACTIVATING IMMUNE RESPONSES AGAINST PATHOGENS, WHICH CAN HELP THE IMMUNE SYSTEM DURING INFECTIONS. HERE, WE PROVIDE AN UPDATED OVERVIEW OF THE ROLES PLAYED BY DIETARY FACTORS AND HOW THEY CAN AFFECT RESPIRATORY HEALTH. THEREFORE, WE WILL SHOW THE ANTI-INFLAMMATORY ROLE OF FLAVONOIDS, FATTY ACIDS, VITAMINS AND MICROBIOTA, IMPORTANT FOR THE CONTROL OF CHRONIC INFLAMMATORY DISEASES AND ALLERGIES, IN ADDITION TO THE ANTIVIRAL ROLE OF VITAMINS, FLAVONOIDS, AND MINERALS DURING PULMONARY VIRAL INFECTIONS, ADDRESSING THE MECHANISMS INVOLVED IN EACH FUNCTION. THESE MECHANISMS ARE INTERESTING IN THE DISCUSSION OF PERSPECTIVES ASSOCIATED WITH SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION AND ITS PULMONARY COMPLICATIONS SINCE PATIENTS WITH SEVERE DISEASE HAVE VITAMINS DEFICIENCY, ESPECIALLY VITAMIN D. IN ADDITION, RESEARCHES WITH THE USE OF FLAVONOIDS HAVE BEEN SHOWN TO DECREASE VIRAL REPLICATION IN VITRO. THIS WAY, A FULL UNDERSTANDING OF DIETARY INFLUENCES CAN IMPROVE THE LUNG HEALTH OF PATIENTS. 2021 10 5410 24 REGULATION OF ADAPTIVE IMMUNE CELLS BY SIRTUINS. IT IS NOW WELL-ESTABLISHED THAT THE PATHWAYS THAT CONTROL LYMPHOCYTE METABOLISM AND FUNCTION ARE INTIMATELY LINKED, AND CHANGES IN LYMPHOCYTE METABOLISM CAN INFLUENCE AND DIRECT CELLULAR FUNCTION. INTERESTINGLY, A NUMBER OF RECENT ADVANCES INDICATE THAT LYMPHOCYTE IDENTITY AND METABOLISM IS PARTIALLY CONTROLLED VIA EPIGENETIC REGULATION. EPIGENETIC MECHANISMS, SUCH AS CHANGES IN DNA METHYLATION OR HISTONE ACETYLATION, HAVE BEEN FOUND TO ALTER IMMUNE FUNCTION AND PLAY A ROLE IN NUMEROUS CHRONIC DISEASE STATES. THERE ARE SEVERAL ENZYMES THAT CAN MEDIATE EPIGENETIC CHANGES; OF PARTICULAR INTEREST ARE SIRTUINS, PROTEIN DEACETYLASES THAT MEDIATE ADAPTIVE RESPONSES TO A VARIETY OF STRESSES (INCLUDING CALORIE RESTRICTION AND METABOLIC STRESS) AND ARE NOW UNDERSTOOD TO PLAY A SIGNIFICANT ROLE IN IMMUNITY. THIS REVIEW WILL FOCUS ON RECENT ADVANCES IN THE UNDERSTANDING OF HOW SIRTUINS AFFECT THE ADAPTIVE IMMUNE SYSTEM. THESE PATHWAYS ARE OF SIGNIFICANT INTEREST AS THERAPEUTIC TARGETS FOR THE TREATMENT OF AUTOIMMUNITY, CANCER, AND TRANSPLANT TOLERANCE. 2019 11 5069 24 PHYSICAL ACTIVITY IN THE PREVENTION OF HUMAN DISEASES: ROLE OF EPIGENETIC MODIFICATIONS. EPIGENETIC MODIFICATION REFERS TO HERITABLE CHANGES IN GENE FUNCTION THAT CANNOT BE EXPLAINED BY ALTERATIONS IN THE DNA SEQUENCE. THE CURRENT LITERATURE CLEARLY DEMONSTRATES THAT THE EPIGENETIC RESPONSE IS HIGHLY DYNAMIC AND INFLUENCED BY DIFFERENT BIOLOGICAL AND ENVIRONMENTAL FACTORS SUCH AS AGING, NUTRIENT AVAILABILITY AND PHYSICAL EXERCISE. AS SUCH, IT IS WELL ACCEPTED THAT PHYSICAL ACTIVITY AND EXERCISE CAN MODULATE GENE EXPRESSION THROUGH EPIGENETIC ALTERNATIONS ALTHOUGH THE TYPE AND DURATION OF EXERCISE ELICITING SPECIFIC EPIGENETIC EFFECTS THAT CAN RESULT IN HEALTH BENEFITS AND PREVENT CHRONIC DISEASES REMAINS TO BE DETERMINED. THIS REVIEW HIGHLIGHTS THE MOST SIGNIFICANT FINDINGS FROM EPIGENETIC STUDIES INVOLVING PHYSICAL ACTIVITY/EXERCISE INTERVENTIONS KNOWN TO BENEFIT CHRONIC DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, CANCER, CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. 2017 12 4972 28 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 13 1400 23 DIET-REGULATING MICROBIOTA AND HOST IMMUNE SYSTEM IN LIVER DISEASE. THE GUT MICROBIOTA HAS BEEN KNOWN TO MODULATE THE IMMUNE RESPONSES IN CHRONIC LIVER DISEASES. RECENT EVIDENCE SUGGESTS THAT EFFECTS OF DIETARY FOODS ON HEALTH CARE AND HUMAN DISEASES ARE RELATED TO BOTH THE IMMUNE REACTION AND THE MICROBIOME. THE GUT-MICROBIOME AND INTESTINAL IMMUNE SYSTEM PLAY A CENTRAL ROLE IN THE CONTROL OF BACTERIAL TRANSLOCATION-INDUCED LIVER DISEASE. DYSBIOSIS, SMALL INTESTINAL BACTERIAL OVERGROWTH, TRANSLOCATION, ENDOTOXEMIA, AND THE DIRECT EFFECTS OF METABOLITES ARE THE MAIN EVENTS IN THE GUT-LIVER AXIS, AND IMMUNE RESPONSES ACT ON EVERY PATHWAYS OF CHRONIC LIVER DISEASE. MICROBIOME-DERIVED METABOLITES OR BACTERIA THEMSELVES REGULATE IMMUNE CELL FUNCTIONS SUCH AS RECOGNITION OR ACTIVATION OF RECEPTORS, THE CONTROL OF GENE EXPRESSION BY EPIGENETIC CHANGE, ACTIVATION OF IMMUNE CELLS, AND THE INTEGRATION OF CELLULAR METABOLISM. HERE, WE REVIEWED RECENT REPORTS ABOUT THE IMMUNOLOGIC ROLE OF GUT MICROBIOTAS IN LIVER DISEASE, HIGHLIGHTING THE ROLE OF DIET IN CHRONIC LIVER DISEASE. 2021 14 6715 29 VITAMIN A AND THE EPIGENOME. THE EPIGENETIC PHENOMENA REFER TO HERITABLE CHANGES IN GENE EXPRESSION OTHER THAN THOSE IN THE DNA SEQUENCE, SUCH AS DNA METHYLATION AND HISTONE MODIFICATIONS. MAJOR RESEARCH PROGRESS IN THE LAST FEW YEARS HAS PROVIDED FURTHER PROOF THAT ENVIRONMENTAL FACTORS, INCLUDING DIET AND NUTRITION, CAN INFLUENCE PHYSIOLOGIC AND PATHOLOGIC PROCESSES THROUGH EPIGENETIC ALTERATIONS, WHICH IN TURN INFLUENCE GENE EXPRESSION. THIS INFLUENCE IS TERMED NUTRITIONAL EPIGENETICS, AND ONE PROMINENT EXAMPLE IS THE REGULATION OF GENE TRANSCRIPTION BY VITAMIN A THROUGH INTERACTION TO ITS NUCLEAR RECEPTOR. VITAMIN A IS CRITICAL THROUGHOUT LIFE. TOGETHER WITH ITS DERIVATIVES, IT REGULATES DIVERSE PROCESSES INCLUDING REPRODUCTION, EMBRYOGENESIS, VISION, GROWTH, CELLULAR DIFFERENTIATION AND PROLIFERATION, MAINTENANCE OF EPITHELIAL CELLULAR INTEGRITY AND IMMUNE FUNCTION. HERE WE REVIEW THE EPIGENETIC ROLE OF VITAMIN A IN CANCER, STEM CELLS DIFFERENTIATION, PROLIFERATION, AND IMMUNITY. THE DATA PRESENTED HERE SHOW THAT RETINOIC ACID IS A POTENT AGENT CAPABLE OF INDUCING ALTERATIONS IN EPIGENETIC MODIFICATIONS THAT PRODUCE VARIOUS EFFECTS ON THE PHENOTYPE. MEDICAL BENEFITS OF VITAMIN A AS AN EPIGENETIC MODULATOR, ESPECIALLY WITH RESPECT TO ITS CHRONIC USE AS NUTRITIONAL SUPPLEMENT, SHOULD RELY ON OUR FURTHER UNDERSTANDING OF ITS EPIGENETIC EFFECTS DURING HEALTH AND DISEASE, AS WELL AS THROUGH DIFFERENT GENERATIONS. 2017 15 2336 27 EPIGENETIC REGULATION OF INFLAMMATORY FACTORS IN ADIPOSE TISSUE. OBESITY IS A STRONG RISK FACTOR FOR INSULIN RESISTANCE. CHRONIC LOW-GRADE TISSUE INFLAMMATION AND SYSTEMIC INFLAMMATION HAVE BEEN PROPOSED AS MAJOR MECHANISMS THAT PROMOTE INSULIN RESISTANCE IN OBESITY. ADIPOSE TISSUE HAS BEEN RECOGNIZED AS A NEXUS BETWEEN INFLAMMATION AND METABOLISM, BUT HOW EXACTLY INFLAMMATORY GENE EXPRESSION IS ORCHESTRATED DURING THE DEVELOPMENT OF OBESITY IS NOT WELL UNDERSTOOD. EPIGENETIC MODIFICATIONS ARE DEFINED AS HERITABLE CHANGES IN GENE EXPRESSION AND CELLULAR FUNCTION WITHOUT CHANGES TO THE ORIGINAL DNA SEQUENCE. THE MAJOR EPIGENETIC MECHANISMS INCLUDE DNA METHYLATION, HISTONE MODIFICATION, NONCODING RNAS, NUCLEOPOSITIONING/REMODELING AND CHROMATIN REORGANIZATION. EPIGENETIC MECHANISMS PROVIDE A CRITICAL LAYER OF GENE REGULATION IN RESPONSE TO ENVIRONMENTAL CHANGES. ACCUMULATING EVIDENCE SUPPORTS THAT EPIGENETICS PLAYS A LARGE ROLE IN THE REGULATION OF INFLAMMATORY GENES IN ADIPOCYTES AND ADIPOSE-RESIDENT IMMUNE CELL TYPES. THIS REVIEW FOCUSES ON THE ASSOCIATION BETWEEN ADIPOSE TISSUE INFLAMMATION IN OBESITY AND MAJOR EPIGENETIC MODIFICATIONS. 2021 16 3669 25 INFLAMMAGING AND CANCER: A CHALLENGE FOR THE MEDITERRANEAN DIET. AGING IS CONSIDERED THE MAJOR RISK FACTOR FOR CANCER, ONE OF THE MOST IMPORTANT MORTALITY CAUSES IN THE WESTERN WORLD. INFLAMMAGING, A STATE OF CHRONIC, LOW-LEVEL SYSTEMIC INFLAMMATION, IS A PERVASIVE FEATURE OF HUMAN AGING. CHRONIC INFLAMMATION INCREASES CANCER RISK AND AFFECTS ALL CANCER STAGES, TRIGGERING THE INITIAL GENETIC MUTATION OR EPIGENETIC MECHANISM, PROMOTING CANCER INITIATION, PROGRESSION AND METASTATIC DIFFUSION. THUS, INFLAMMAGING IS A STRONG CANDIDATE TO CONNECT AGE AND CANCER. A COROLLARY OF THIS HYPOTHESIS IS THAT INTERVENTIONS AIMING TO DECREASE INFLAMMAGING SHOULD PROTECT AGAINST CANCER, AS WELL AS MOST/ALL AGE-RELATED DISEASES. EPIDEMIOLOGICAL DATA ARE CONCORDANT IN SUGGESTING THAT THE MEDITERRANEAN DIET (MD) DECREASES THE RISK OF A VARIETY OF CANCERS BUT THE UNDERPINNING MECHANISM(S) IS (ARE) STILL UNCLEAR. HERE WE REVIEW DATA INDICATING THAT THE MD (AS A WHOLE DIET OR SINGLE BIOACTIVE NUTRIENTS TYPICAL OF THE MD) MODULATES MULTIPLE INTERCONNECTED PROCESSES INVOLVED IN CARCINOGENESIS AND INFLAMMATORY RESPONSE SUCH AS FREE RADICAL PRODUCTION, NF-KAPPAB ACTIVATION AND EXPRESSION OF INFLAMMATORY MEDIATORS, AND THE EICOSANOIDS PATHWAY. PARTICULAR ATTENTION IS DEVOTED TO THE CAPABILITY OF MD TO AFFECT THE BALANCE BETWEEN PRO- AND ANTI-INFLAMMAGING AS WELL AS TO EMERGING TOPICS SUCH AS MAINTENANCE OF GUT MICROBIOTA (GM) HOMEOSTASIS AND EPIGENETIC MODULATION OF ONCOGENESIS THROUGH SPECIFIC MICRORNAS. 2015 17 6067 36 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 18 1411 30 DIETARY NATURAL PRODUCTS AS EPIGENETIC MODIFIERS IN AGING-ASSOCIATED INFLAMMATION AND DISEASE. COVERING: UP TO 2020CHRONIC, LOW-GRADE INFLAMMATION IS LINKED TO AGING AND HAS BEEN TERMED "INFLAMMAGING". INFLAMMAGING IS CONSIDERED A KEY CONTRIBUTOR TO THE DEVELOPMENT OF METABOLIC DYSFUNCTION AND A BROAD SPECTRUM OF DISEASES OR DISORDERS INCLUDING DECLINES IN BRAIN AND HEART FUNCTION. GENOME-WIDE ASSOCIATION STUDIES (GWAS) COUPLED WITH EPIGENOME-WIDE ASSOCIATION STUDIES (EWAS) HAVE SHOWN THE IMPORTANCE OF DIET IN THE DEVELOPMENT OF CHRONIC AND AGE-RELATED DISEASES. MOREOVER, DIETARY INTERVENTIONS E.G. CALORIC RESTRICTION CAN ATTENUATE INFLAMMATION TO DELAY AND/OR PREVENT THESE DISEASES. COMMON THEMES IN THESE STUDIES ENTAIL THE USE OF PHYTOCHEMICALS (PLANT-DERIVED COMPOUNDS) OR THE PRODUCTION OF SHORT CHAIN FATTY ACIDS (SCFAS) AS EPIGENETIC MODIFIERS OF DNA AND HISTONE PROTEINS. EPIGENETIC MODIFICATIONS ARE DYNAMICALLY REGULATED AND AS SUCH, SERVE AS POTENTIAL THERAPEUTIC TARGETS FOR THE TREATMENT OR PREVENTION OF AGE-RELATED DISEASE. IN THIS REVIEW, WE WILL FOCUS ON THE ROLE FOR NATURAL PRODUCTS THAT INCLUDE PHYTOCHEMICALS AND SHORT CHAIN FATTY ACIDS (SCFAS) AS REGULATORS OF THESE EPIGENETIC ADAPTATIONS. SPECIFICALLY, WE DISCUSS REGULATORS OF METHYLATION, ACETYLATION AND ACYLATION, IN THE PROTECTION FROM CHRONIC INFLAMMATION DRIVEN METABOLIC DYSFUNCTION AND DETERIORATION OF NEUROCOGNITIVE AND CARDIAC FUNCTION. 2020 19 6034 29 THE CHALLENGE BY MULTIPLE ENVIRONMENTAL AND BIOLOGICAL FACTORS INDUCE INFLAMMATION IN AGING: THEIR ROLE IN THE PROMOTION OF CHRONIC DISEASE. THE AGING PROCESS IS DRIVEN BY MULTIPLE MECHANISMS THAT LEAD TO CHANGES IN ENERGY PRODUCTION, OXIDATIVE STRESS, HOMEOSTATIC DYSREGULATION AND EVENTUALLY TO LOSS OF FUNCTIONALITY AND INCREASED DISEASE SUSCEPTIBILITY. MOST AGED INDIVIDUALS DEVELOP CHRONIC LOW-GRADE INFLAMMATION, WHICH IS AN IMPORTANT RISK FACTOR FOR MORBIDITY, PHYSICAL AND COGNITIVE IMPAIRMENT, FRAILTY, AND DEATH. AT ANY AGE, CHRONIC INFLAMMATORY DISEASES ARE MAJOR CAUSES OF MORBIMORTALITY, AFFECTING UP TO 5-8% OF THE POPULATION OF INDUSTRIALIZED COUNTRIES. SEVERAL ENVIRONMENTAL FACTORS CAN PLAY AN IMPORTANT ROLE FOR MODIFYING THE INFLAMMATORY STATE. GENETICS ACCOUNTS FOR ONLY A SMALL FRACTION OF CHRONIC-INFLAMMATORY DISEASES, WHEREAS ENVIRONMENTAL FACTORS APPEAR TO PARTICIPATE, EITHER WITH A CAUSATIVE OR A PROMOTIONAL ROLE IN 50% TO 75% OF PATIENTS. SEVERAL OF THOSE CHANGES DEPEND ON EPIGENETIC CHANGES THAT WILL FURTHER MODIFY THE INDIVIDUAL RESPONSE TO ADDITIONAL STIMULI. THE INTERACTION BETWEEN INFLAMMATION AND THE ENVIRONMENT OFFERS IMPORTANT INSIGHTS ON AGING AND HEALTH. THESE CONDITIONS, OFTEN DEPENDING ON THE INDIVIDUAL'S SEX, APPEAR TO LEAD TO DECREASED LONGEVITY AND PHYSICAL AND COGNITIVE DECLINE. IN ADDITION TO BIOLOGICAL FACTORS, THE ENVIRONMENT IS ALSO INVOLVED IN THE GENERATION OF PSYCHOLOGICAL AND SOCIAL CONTEXT LEADING TO STRESS. POOR PSYCHOLOGICAL ENVIRONMENTS AND OTHER SOURCES OF STRESS ALSO RESULT IN INCREASED INFLAMMATION. HOWEVER, THE MECHANISMS UNDERLYING THE ROLE OF ENVIRONMENTAL AND PSYCHOSOCIAL FACTORS AND NUTRITION ON THE REGULATION OF INFLAMMATION, AND HOW THE RESPONSE ELICITED FOR THOSE FACTORS INTERACT AMONG THEM, ARE POORLY UNDERSTOOD. WHEREAS CERTAIN DELETERIOUS ENVIRONMENTAL FACTORS RESULT IN THE GENERATION OF OXIDATIVE STRESS DRIVEN BY AN INCREASED PRODUCTION OF REACTIVE OXYGEN AND NITROGEN SPECIES, ENDOPLASMIC RETICULUM STRESS, AND INFLAMMATION, OTHER FACTORS, INCLUDING NUTRITION (POLYUNSATURATED FATTY ACIDS) AND BEHAVIORAL FACTORS (EXERCISE) CONFER PROTECTION AGAINST INFLAMMATION, OXIDATIVE AND ENDOPLASMIC RETICULUM STRESS, AND THUS AMELIORATE THEIR DELETERIOUS EFFECT. HERE, WE DISCUSS PROCESSES AND MECHANISMS OF INFLAMMATION ASSOCIATED WITH ENVIRONMENTAL FACTORS AND BEHAVIOR, THEIR LINKS TO SEX AND GENDER, AND THEIR OVERALL IMPACT ON AGING. 2020 20 2168 23 EPIGENETIC MECHANISMS IN MONOCYTES/MACROPHAGES REGULATE INFLAMMATION IN CARDIOMETABOLIC AND VASCULAR DISEASE. CARDIOMETABOLIC AND VASCULAR DISEASE, WITH THEIR ASSOCIATED SECONDARY COMPLICATIONS, ARE THE LEADING CAUSE OF MORBIDITY AND MORTALITY IN WESTERN SOCIETY. CHRONIC INFLAMMATION IS A COMMON THEME THAT UNDERLIES INITIATION AND PROGRESSION OF CARDIOVASCULAR DISEASE. IN THIS REGARD, MONOCYTES/MACROPHAGES ARE KEY PLAYERS IN THE DEVELOPMENT OF A CHRONIC INFLAMMATORY STATE. OVER THE PAST DECADE, EPIGENETIC MODIFICATIONS, SUCH AS DNA METHYLATION AND POSTTRANSLATIONAL HISTONE PROCESSING, HAVE EMERGED AS IMPORTANT REGULATORS OF IMMUNE CELL PHENOTYPES. ACCUMULATING STUDIES REVEAL THE IMPORTANCE OF EPIGENETIC ENZYMES IN THE DYNAMIC REGULATION OF KEY SIGNALING PATHWAYS THAT ALTER MONOCYTE/MACROPHAGE PHENOTYPES IN RESPONSE TO ENVIRONMENTAL STIMULI. IN THIS REVIEW, WE HIGHLIGHT THE CURRENT PARADIGMS OF MONOCYTE/MACROPHAGE POLARIZATION AND THE EMERGING ROLE OF EPIGENETIC MODIFICATION IN THE REGULATION OF MONOCYTE/MACROPHAGE PHENOTYPE IN OBESITY, DIABETES MELLITUS, ATHEROSCLEROSIS, AND ABDOMINAL AORTIC ANEURYSMS. 2019