Mechanisms of Lipotoxicity in the Cardiovascular System

Abstract

Cardiovascular diseases account for approximately one third of all deaths globally. Obese and diabetic patients have a high likelihood of dying from complications associated with cardiovascular dysfunction. Obesity and diabetes increase circulating lipids that upon tissue uptake, may be stored as triglyceride, or may be metabolized in other pathways, leading to the generation of toxic intermediates. Excess lipid utilization or activation of signaling pathways by lipid metabolites may disrupt cellular homeostasis and contribute to cell death, defining the concept of lipotoxicity. Lipotoxicity occurs in multiple organs, including cardiac and vascular tissues, and a number of specific mechanisms have been proposed to explain lipotoxic tissue injury. In addition, recent data suggests that increased tissue lipids may also be protective in certain contexts. This review will highlight recent progress toward elucidating the relationship between nutrient oversupply, lipotoxicity, and cardiovascular dysfunction. The review will focus in two sections on the vasculature and cardiomyocytes respectively.

Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart

“…These observations are consistent with skeletal muscle studies in patients with type 2 diabetes, indicating a threefold higher lipid accumulation specifically at the sarcolemma that can be reduced by an exercise training intervention (24). Taken together, these results support the contention that a lipotoxicity-driven mechanism contributes to mitochondrial dysfunction in type 2 diabetic muscle, (31,36) particularly in the subsarcolemmal locale. With that being said, one must consider that the con- …”

Curcumin protects hearts from FFA-induced injury by activating Nrf2 and inactivating NF-κB both in vitro and in vivo

“…Recent studies have emphasized that oxidative stress and chronic inflammatory processes are important in the pathophysiology of obesity-related cardiovascular disorder [4]. Uncontrolled production of ROS and inflammatory cytokines induced by hyperlipidemia impairs cellular functions and causes cell apoptosis in a variety of tissues including the heart [28]. Therefore, elucidating the mechanism by which hyperlipidemia causes cardiac injury and discovering novel therapeutic agents are timely.…”

Effect of aerobic exercise on blood lipid and glucose in obese or overweight adults: A meta-analysis of randomised controlled trials

“…Meanwhile, the fatty acid oxidation can be increased by daily AE in humans and rats [36,37]. Moreover, the increased fatty acid oxidation is benefit for reducing lipotoxicity and cardiovascular diseases risk in humans [38,39]. In addition, it was reported that AE had inhibition effect on the accumulation of TGrich lipoproteins in postmenopausal women [40], which may be caused by enhancing the affinity of TG-rich lipoproteins for lipoprotein lipase [41].…”