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Energy imbalance resulting from high calorie food intake and insufficient metabolic activity leads to increased body mass index (BMI) and sets the stage for metabolic derangement influencing lipid and carbohydrate metabolism and ultimately leading to insulin resistance, dyslipidemia, and type 2 diabetes. 70% of cardiovascular disease (CVD) deaths occur in patients with diabetes. Environment-induced physiological perturbations trigger epigenetic changes through chromatin modification and leads to type 2 diabetes and progression of nonalcoholic fatty liver disease (NAFLD) and CVD. Thus, in terms of disease progression and pathogenesis, energy homeostasis, metabolic dysregulation, diabetes, fatty liver, and CVD are interlinked. Since advanced glycation end products (AGEs) and low-grade inflammation in type 2 diabetes play definitive roles in the pathogenesis of liver and vascular diseases, a natural checkpoint to prevent diabetes and associated complications appears to be the identification and management of prediabetes together with weight management, since 70% of prediabetic individuals develop diabetes during their life time, and every kg of weight increase is associated with up to 9% increase in diabetes risk. A good proportion of diabetes and obesity population have fatty liver that progresses to non-alcoholic steatohepatitis (NASH) and cirrhosis, and increased risk of hepatocellular carcinoma. Diabetes and NASH both have elevated oxidative stress, impaired cholesterol elimination, and increased inflammation that leads to CVD risk. This review addresses life-style-induced metabolic pathway derangement and how it contributes to epigenetic changes, type 2 diabetes and NASH progression, which collectively lead to increased risk of CVD.
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Cavan DHJ, Linnenkamp U, Makaroff L, Magliano D, Ogurtrstova K, Shaw J. Diabetes and cardiovascular disease. International Diabetes Federation 2016;1–12. http://www.idforg/cvd. Accessed 9 Aug 2018.
Feingold KR, Grunfeld C. Obesity and dyslipidemia. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext. South Dartmouth (MA): MDText.com, Inc., 2000. Acessed 10 April 2018.
Srivastava RA, Srivastava N. Search for obesity drugs: targeting central and peripheral pathways. Curr Med Chem Immunol Endocr Metab Agents. 2004;4:75–90. CrossRef
Zafar U, Khaliq S, Ahmad HU, Manzoor S, Lone KP. Metabolic syndrome: an update on diagnostic criteria, pathogenesis, and genetic links. Hormones (Athens, Greece). 2018;17:299–313. CrossRef
Riserus U, Sprecher D, Johnson T, Olson E, Hirschberg S, Liu A, et al. Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men. Diabetes. 2008;57:332–9. PubMedCrossRef
Oorni K, Lehti S, Sjovall P, Kovanen PT. Triglyceride-rich lipoproteins as a source of proinflammatory lipids in the arterial wall. Curr Med Chem. 2018
Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898–918. PubMedCrossRefPubMedCentral
Eckel RH. CVD health factors and CVD risk factors: state of the science, emerging priorities part 2: obesity prevention. Ethn Dis. 2012;22:S1–36–40.
Mooradian AD, Haas MJ, Wehmeier KR, Wong NC. Obesity-related changes in high-density lipoprotein metabolism. Obesity (Silver Spring). 2008;16:1152–60. CrossRef
Basciano H, Miller AE, Naples M, Baker C, Kohen R, Xu E, et al. Metabolic effects of dietary cholesterol in an animal model of insulin resistance and hepatic steatosis. Am J Phys Endocrinol Metab. 2009;297:E462–73. CrossRef
Anjana RM, Pradeepa R, Deepa M, et al. Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in urban and rural India: phase I results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study. Diabetologia. 2011;54:3022–7. PubMedCrossRef
Chambon P. Determination of the organization of coding and intervening sequences in the chicken ovalbumin split gene. Differentiation. 1979;13:43–4.
Crick F. Split genes and RNA splicing. Science (New York, NY). 1979;204:264–71. CrossRef
Khullar M, Cheema BS, Raut SK. Emerging evidence of epigenetic modifications in vascular complication of diabetes. Front Endocrinol. 2017;8:237. CrossRef
Clouaire T, Stancheva I. Methyl-CpG binding proteins: specialized transcriptional repressors or structural components of chromatin? Cell Mol Life Sc. 2008;65:1509–22.
Datz C, Muller E, Aigner E. Iron overload and non-alcoholic fatty liver disease. Minerva Endocrinol. 2017;42:173–83. PubMed
Carr RM, Oranu A, Khungar V. Nonalcoholic fatty liver disease: pathophysiology and management. Gastroenterol Clin N Am. 2016;45:639–52. CrossRef
Kohjima M, Enjoji M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, et al. Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med. 2007;20:351–8. PubMed
Thayer TEMT, Shakartzi H, Wunderer F, Perrien D, Farber-Eger E, Burke M, et al. Inhibition of bone morphogenetic protein (BMP) signaling mitigates nonalcoholic fatty liver disease (NAFLD) and identification of an activating BMP receptor polymorphism associated with NAFLD. Circulation. 2017;136:A16421.
Barlovic DP, Soro-Paavonen A, Jandeleit-Dahm KA. RAGE biology, atherosclerosis and diabetes. Clin Sci (Lond). 2011;121:43–55. CrossRef
Srivastava R, Cefalu, AB, Davide, A, Averna MR. A Combination of Metformin, Quercetin, and Curcumin Restores HDL Function and Improves Atherosclerosis Burden in LDLr−/−/ob.ob leptin−/− and LDLr−/− Mice by attenuating Inseulin Resistance, Hyperglycemia, and Low-grade Inflammation ATVB Scientific Session 2013:Abstract.
Srivastava RAK. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Mol Cell Biochem. 2018;440:167–187.
Salomaa V, Riley W, Kark JD, Nardo C, Folsom AR. Non-insulin-dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes. The ARIC study. Atherosclerosis risk in communities study. Circulation. 1995;91:1432–43. PubMedCrossRefPubMedCentral
Chalasani N, Younossi Z, Lavine JE et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2017.
- Life-style-induced metabolic derangement and epigenetic changes promote diabetes and oxidative stress leading to NASH and atherosclerosis severity
Rai Ajit K. Srivastava
- Springer International Publishing
Journal of Diabetes & Metabolic Disorders
Elektronische ISSN: 2251-6581
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