Why does obesity increase the risk for cardiovascular disease?
1Division of Endocrinology, Diabetes, Metabolism and the Clinical Research Center, Temple University School of Medicine, Philadelphia, PA, USA. bodengh@tuhs.temple.edu
Current Pharmaceutical Design
|March 2, 2013
Summary
Obesity links to cardiovascular disease (CVD) via insulin resistance and inflammation. Endoplasmic reticulum stress explains these issues in all obese individuals, even without high free fatty acids, and hyperinsulinemia may directly promote CVD.
Area of Science:
- Metabolic disease
- Cardiovascular science
Background:
- Insulin resistance and inflammation link obesity to cardiovascular disease (CVD).
- Plasma free fatty acids (FFA) contribute to insulin resistance and inflammation, which are linked to type 2 diabetes, hypertension, dyslipidemia, and coagulation disorders.
Purpose of the Study:
- To explore mechanisms linking obesity, insulin resistance, inflammation, and cardiovascular disease.
- To evaluate the role of endoplasmic reticulum (ER) stress and hyperinsulinemia in CVD development.
Main Methods:
- Review of hypotheses explaining FFA-induced insulin resistance (lipid metabolite, inflammation, hyperinsulinemia, ER stress).
- Examination of evidence supporting hyperinsulinemia as a direct cause of CVD.
Main Results:
- Endoplasmic reticulum (ER) stress offers a mechanism for insulin resistance and inflammation in all obese individuals, irrespective of plasma FFA levels.
- Emerging evidence suggests chronic hyperinsulinemia directly promotes CVD by activating triglyceride formation, matrix metalloproteinases (MMP), and coagulation pathways.
Conclusions:
- ER stress is a unifying mechanism for obesity-related insulin resistance and inflammation.
- Hyperinsulinemia, independent of metabolic insulin resistance, is implicated in cardiovascular disease pathogenesis.
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