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Life-style-induced metabolic derangement and epigenetic changes promote diabetes and oxidative stress leading to NASH and atherosclerosis severity

  • Rai Ajit K. SrivastavaEmail author
Review Article
  • 30 Downloads

Abstract

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.

Keywords

Life-style Diabetes Epigenetic Cardiovascular NASH Inflammation Atherosclerosis 

Abbreviations

VLDL

very low-density lipoprotein

LDL

low-density lipoprotein

HDL

high-density lipoprotein

CVD

cardiovascular disease

NAFLD

non-alcoholic fatty liver disease

AGE

advanced glycation end-products

NASH

non-alcoholic steatohepatitis

MetS

metabolic syndrome

apoA-I

apolipoprotein A-I

BMI

body mass index

miR

micro RNA

COPD

chronic obstructive pulmonary disease

HAT

histone deacetylase

HDAC

histone acetyl transferase

T2DM

type 2 diabetes mellitus

VSMC

Vascular smooth muscle cells

MCP1

monocyte chemoattractant protein 1

LSD-1

lysine-specific demethylase

VCAM1

vascular cell adhesion molecule 1

NF-κB

nuclear factor kappa B

Cox2

cyclooxygenase 2

TNF-α

tumor necrosis factor-α

FXR

farnesoid X receptor

TRL

triglyceride-rich lipoproteins

RCT

reverse cholesterol transport

SR-BI

scavenger receptor class B type 1

ABCA1

ATP binding cassette transporter 1

HbA1c

hemoglobin A1c

RAGE

receptor for advanced glycation end-products

Notes

Compliance with ethical standards

Conflict of interest

The author declares that there is no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Integrated Pharma SolutionsPhiladelphiaUSA
  2. 2.Department of NutritionWayne State UniversityDetroitUSA

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