Adiponectin resistance and vascular dysfunction in the hyperlipidemic state

Abstract

Insulin plays an important role in the stimulation of vascular nitric oxide production, with both short term (vasomotility and antithrombotic effects) and long term (smooth muscle cell growth and migration inhibition) benefits. Impaired vasodilatory response to insulin, the hallmark of vascular insulin resistance (IR), has important implications for circulatory pathophysiology. An association between adipokines and IR has been observed in both diabetic and nondiabetic states. Adiponectin (APN) is an insulin-sensitizing adipokine known to stimulate skeletal muscle fatty acid (FA) oxidation and reduce lipid accumulation. Recent demonstrations of potential cross-talk between APN and insulin in vascular function regulation are particularly interesting. The lipid accumulation observed after chronic high-fat (HF) diets and in the obese state may reduce vascular response to APN, a pathologic state termed as APN resistance. This review highlights the importance of insulin sensitivity and APN activity in the maintenance of endothelial function. It explores the relationships between vascular IR and APN resistance in the hyperlipidemic pathological condition, representative of the metabolic syndrome. The investigation of vascular insulin and APN resistance provides not only better understanding of vascular pathophysiology, but also an opportunity for therapeutic targeting in individuals affected by the metabolic syndrome.

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

“…2 The high correlation noted between HMW adiponectin and adiponectin (total) confirmed the representativeness of adiponectin in surveying insulin sensitivity. 8 Although adiponectin is regarded as an insulin-sensitizing adipokine that metabolically mimics insulin, 10 the connection between pre-therapy adiponectin and HOMA-IR levels was not a direct association but rather was mediated through TGs (Fig. 1).…”

“…35 Thus, the opposing trends of HOMA-IR levels between those with and without baseline IR after SVR were particularly notable. Because adiponectin enhances insulin sensitivity and counteracts IR in animal studies, 10,38 the decreased adiponectin after SVR should cause the increase in HOMA-IR levels as observed in patients without baseline IR. By contrast, a comprehensive review failed to demonstrate modulation of adiponectin in human insulin sensitivity.…”

“…9 Adiponectin and its receptors might protect hepatocytes from triglyceride accumulation by increasing b-oxidation, decreasing the de novo synthesis of fatty acids, and promoting the uptake and inhibiting the production of glucose in the liver. [10][11] Thus, hepatitis steatosis is usually associated with low levels of adiponectin. 11 In addition, statin-inducted hypolipidemia is associated with hyperadiponectinemia.…”

Cardiovascular Risk Factors in Children with Obesity, Preventive Diagnostics and Possible Interventions

“…Due to its decreased concentration in obesity, these pathways are disrupted, thus promoting vascular dysfunction. This has also been proven by alleviation of vascular dysfunction in animal models when adiponectin is added [ 20 , 21 , 22 ]. Ghrelin is another hormone that is decreased in obesity, since its function is to increase food intake.…”

Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology

“…An additional question that would need to be addressed is: if adiponectin generally has protective properties why would high circulating adiponectin levels not improve or decrease the dementia risk? One possibility is that the high circulating adiponectin levels leads to subsequent resistance to adiponectin in a similar fashion to insulin resistance and leptin resistance [116,117]. While showing an association between high plasma adiponectin and dementia, these findings are still controversial.…”