Relationships between adiponectin levels, the metabolic syndrome, and type 2 diabetes: a literature review

Abstract

Elevated hepatic glucose production, impaired insulin secretion, and insulin resistance - abnormalities of glucose metabolism typically found in subjects with obesity - are major factors underlying the pathogenesis of type 2 diabetes (DM2) and the metabolic syndrome (MS). Adiponectin is a major regulator of glucose and lipid homeostasis via its insulin-sensitizing properties, and lower levels seems to be associated with the development of DM2 and MS. The purpose of this review is to clarify the mechanisms whereby adiponectin relates to the development of DM2 and MS and the association between polymorphisms of the adiponectin gene, circulating levels of the hormone, and its relationships with DM2. In addition, the impact of dietary lipids in the circulating levels of adiponectin will be addressed. According to the literature, circulating adiponectin levels seem to decrease as the number of MS components increases. Lower adiponectin concentrations are associated with higher intra-abdominal fat content. Therefore, adiponectin could link intra-abdominal fat with insulin resistance and development of MS. Therapeutic strategies that target the MS and its components, such as lifestyle modification through physical activity and weight loss, have been shown to increase adiponectin concentrations. Possible roles of diets containing either low or high amounts of fat, or different types of fat, have been analyzed in several studies, with heterogeneous results. Supplementation with n-3 PUFA modestly increases adiponectin levels, whereas conjugated linoleic acid supplementation appears to reduce concentrations when compared with unsaturated fatty acid supplementation used as an active placebo.

Figure 1. Mechanisms whereby a reduction in adiponectin levels is associated with the development of MS. 1: Accumulation of visceral fat reduces production of adiponectin. Tissue inflammation increases levels of C-reactive protein (CRP) and inflammatory cytokines (TNF-α and interleukin-6), activating hepatic gluconeogenesis. 2: Hepatic gluconeogenesis is activated and insulin sensitivity in muscle and liver is further reduced, resulting in increased circulating glucose levels. 3 and 4: Reduction of triglyceride oxidation from adipose tissue and dietary lipids by the liver increases levels of free fatty acids (FFA) and production of VLDL, generating an imbalance in lipid profile (increased LDL cholesterol, triglycerides [TG], and reduced HDL cholesterol). 5: Increased serum level of procollagen type I carboxy-terminal propeptide (PICP) intensifies arterial stiffness, and reduced nitric oxide production contributes to reduced vasodilation. These mechanisms, along with the pro-inflammatory environment, promote changes in blood pressure homeostasis, which contribute to the development of systemic arterial hypertension.