Impact of Obesity-Related Inflammation on Cardiac Metabolism and Function

Abstract

This review focuses on the role of adipose tissue in obese individuals in the development of metabolic diseases, and their consequences for metabolic and functional derangements in the heart. The general idea is that the expansion of adipocytes during the development of obesity gives rise to unhealthy adipose tissue, characterized by low-grade inflammation and the release of proinflammatory adipokines and fatty acids (FAs). This condition, in turn, causes systemic inflammation and elevated FA concentrations in the circulation, which links obesity to several pathologies, including impaired insulin signaling in cardiac muscle and a subsequent shift in myocardial substrate oxidation in favor of FAs and reduced cardiac efficiency. This review also argues that efforts to prevent obesity-related cardiometabolic disease should focus on anti-obesogenic strategies to restore normal adipose tissue metabolism.

Keywords: Heart; Inflammation; Lipid metabolism; Oxygen consumption; Visceral adipose tissue.

Fig. 1. Increasing visceral obesity causes inflammatory responses and metabolic dysregulation in fat and liver tissue. This condition involves infiltration of monocytes and macrophages and subsequent secretion of pro-inflammatory adipokines and elevated release of free fatty acids, leading to systemic inflammation, which promotes insulin resistance in several organs, including the heart. In addition, an elevated supply of lipids (free and esterified fatty acids) exceeds the fatty acid oxidation capacity and causes lipotoxicity in the myocardium, eventually leading to cardiac dysfunction.

Fig. 2. Age-dependent changes in myocardial substrate oxidation and ventricular function in control (db/+, red columns) and type 2 diabetic (db/db, yellow columns) mice. (A) Reduction of glucose oxidation in db/db hearts after 10–12 weeks, while fatty acid oxidation had already significantly increased at 6 weeks (B), preceding the decline of left ventricular function (C), measured as PSP times CO. Modified from Aasum et al.

PSP, peak systolic pressure; CO, cardiac output. ^*p<0.05 vs. db/+; ^†p<0.05 vs. 6 week.

Fig. 3. Increased myocardial oxygen consumption and ventricular dysfunction in DIO mice. (A) Relationship between MVO₂ and total cardiac work (measured as PVA) in isolated perfused hearts from lean CON (red line) and DIO mice (yellow line). (B) The increased oxygen consumption of the DIO hearts is explained by increased oxygen cost for excitation-contraction coupling as well as for basal metabolism. (C) Leftward shift of the pressure-volume loop of DIO heart relative to control, indicating concentric remodeling and ventricular stiffness. Modified from Hafstad et al.

MVO₂, myocardial oxygen consumption; PVA, pressure-volume area; CON, control; DIO, diet-induced obese; LV, left ventricular. ^*p<0.05 vs. CON.