Adiponectin, Leptin and Cardiovascular Disorders

Abstract

The landmark discoveries of leptin and adiponectin firmly established adipose tissue as a sophisticated and highly active endocrine organ, opening a new era of investigating adipose-mediated tissue crosstalk. Both obesity-associated hyperleptinemia and hypoadiponectinemia are important biomarkers to predict cardiovascular outcomes, suggesting a crucial role for adiponectin and leptin in obesity-associated cardiovascular disorders. Normal physiological levels of adiponectin and leptin are indeed essential to maintain proper cardiovascular function. Insufficient adiponectin and leptin signaling results in cardiovascular dysfunction. However, a paradox of high levels of both leptin and adiponectin is emerging in the pathogenesis of cardiovascular disorders. Here, we (1) summarize the recent progress in the field of adiponectin and leptin and its association with cardiovascular disorders, (2) further discuss the underlying mechanisms for this new paradox of leptin and adiponectin action, and (3) explore the possible application of partial leptin reduction, in addition to increasing the adiponectin/leptin ratio as a means to prevent or reverse cardiovascular disorders.

Keywords: adiponectin; cardiovascular diseases; hypoadiponectinemia; leptin; obesity.

Figure 1:

The paradoxical effects of adiponectin and leptin in regulating cardiovascular function. Low levels of adiponectin and leptin are positively associated with severe cardiovascular disorders. Thus, it is predicted that high adiponectin and leptin levels, beyond physiological (normal) levels, would lead to a much improved cardiovascular function, as shown in the red dashed curve. However, in most cases, high circulating leptin and adiponectin levels do not show any beneficial effects, but rather can be detrimental for cardiovascular function, similar to the conditions with low circulating levels, as shown in the green area, referred to as “paradoxical” effects.

Figure 2.

Relationship between body weight, fat mass, circulating leptin and adiponectin levels with cardiovascular function. The gradual transition from lean to overweight to obesity is associated with a dramatic adipose tissue expansion. During this process, circulating leptin and adiponectin levels are altered accordingly. Low adiponectin and high leptin levels eventually negatively affect cardiovascular function.

Figure 3.

Relationship of circulating leptin levels and cardiovascular dysfunction. For proper cardiovascular function, circulating leptin levels are required to maintain in a narrow normal range. Under conditions of lipodystrophy, caused by widespread adipose tissue apoptosis or an inability to properly develop adipose tissue, extremely low levels of circulating leptin promote cardiovascular disorders, which can be reversed by leptin therapy; Under conditions of diet-induced obesity, hyperleptinemia is a driving force for cardiovascular dysfunction due to leptin resistance, which can be restored by reducing circulating leptin levels (“partial leptin reduction”).