The Clinical Implications of Blood Adiponectin in Cardiometabolic Disorders

Abstract

Adipose tissue is now accepted by the scientific and medical community to be a genuine endocrine organ, in addition to its classical role as an energy store. Adiponectin is one of the many adipocytokines that are secreted almost exclusively by adipose tissue. Alteration in blood adiponectin concentrations has been linked to many human diseases in numerous cross-sectional and prospective studies. In this review, we describe briefly the biological effects of adiponectin as revealed by basic scientific investigations. We also summarize the principles of blood adiponectin assays. Overall, lower blood adiponectin concentration is found in subjects with obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension. These medical conditions are components of the metabolic syndrome and major risk factors for accelerated atherosclerosis. Plasma adiponectin levels are also expected to be lower in subjects with cardiovascular diseases, such as coronary artery disease, ischemic stroke and peripheral artery disease. Congestive heart failure (CHF) and cardiac arrhythmia are common end points in cardiovascular diseases. Surprisingly, higher blood adiponectin levels are frequently reported to predict mortality associated with CHF. Few human data regarding adiponectin and cardiac arrhythmia are available. Higher blood adiponectin level has been documented only in atrial fibrillation. We also summarize data on the role of the high molecular weight (HMW) isoforms of adiponectin and the effects of clinical treatment on the levels of total or HMW adiponectin. Whether adiponectin is a risk marker or a risk factor for the diseases reviewed in this article, and in many other human diseases, and their detailed pathogenic links awaits further investigation.

Hypoadiponectinemia in Obesity: Association with Insulin Resistance

“…The negative relationship was reported between adiponectin and insulin resistance in type 2 diabetes [22] and in insulin-resistant subjects [23]. The role of adiponectin on the pathogenesis of insulin resistance is at this time not well understood.…”

Total Adiponectin Levels in Dyslipidemic Individuals: Relationship to Metabolic Parameters and Intima-Media Thickness

“…The close negative relationship between insulin resistance and adiponectin was found in type 2 diabetes 5,13,14 and in insulin-resistant state 5,13,35,36 . Although epidemiological and experimental studies have found an association between insulin resistance and low plasma adiponectin levels, it has not been established whether decreased adiponectin levels are the cause or the effect of this dysregulated metabolic state.…”

“…A large number of studies have confirmed a positive correlation between plasma adiponectin and HDL-C, or apo A1 and an inverse relationship with TG (ref. 5,[12][13][14][17][18][19][29][30][31] ). The mechanism linking plasma adiponectin and apoA1 has not been fully clarified.…”

“…Adiponectin accumulates in the arterial wall of injured arteries 9 , suppresses lipid accumulation and inhibits macrophages to foam-cell transformation 10 and smooth muscle cell proliferation 11 . Low levels of adiponectin were found in subjects with obesity 12,13 , type 2 diabetes mellitus 13,14 , hypertension 15,16 and dyslipidemia 5,[17][18][19] . Initially, low levels of adiponectin were also found in patients with coronary artery disease independently of other risk factors 20,21 .…”

“…3,4 ). Although some studies have proposed that the ratio of the HMW to other forms may serve as a better indicator of metabolic disorders, the majority of studies that have linked adiponectin to metabolic diseases have used assays for total adiponectin 5 . Adiponectin has an insulin-sensitizing effect on hepatocytes -leading to hepatic glucose output suppression 6 and on muscles -by stimulating fattyacid oxidation 7 .…”