Elsevier

Medical Hypotheses

Volume 73, Issue 6, December 2009, Pages 981-985
Medical Hypotheses

Adipocytokines: A bridge connecting obesity and insulin resistance

https://doi.org/10.1016/j.mehy.2009.05.036Get rights and content

Summary

Overweight or obesity has become a critical health problem in the world. The association of obesity with type 2 diabetes mellitus (T2D) has been recognized for decades, and the major basis for this link is the ability of obesity to engender insulin resistance (IR). Adipose tissue is not only an energy depot but also an active endocrine organ. Furthermore, fat distribution in the body is important for the progress of IR. Many studies show that visceral fat is more important in relation to IR than subcutaneous fat. Circulating free fatty acids (FFAs) derived from adipocytes are elevated in many IR states and have been suggested to be a main underlying mechanism of IR in obesity-associated T2D. However, compelling evidence demonstrates that adipocytokines including several adipocyte-derived cytokines or hormones are also involved in obesity-induced IR. Therefore, we hypothesise that adipocytokines may be a bridge connecting obesity and IR, and abnormal fat depot distribution or visceral fat/subcutaneous fat ratio (V/S ratio) in obesity also could be a primer for IR. When visceral fat accumulates and V/S ratio deteriorates , just like a primer,in visceral obesity it should begin to display unhealthy effect begin to take place in the body. In addition to it, as one of physiological regulation mechanisms of the body, most of the adipocytokines from the visceral fat reduce the visceral fat volume or normalize the V/S ratio. Actually, on the contrary, with serum a change in the serum adipocytokine level and an imbalance of them in the body for a long term, it will become a pathological condition and various kinds of effects may contribute to the development of IR. If confirmed, this hypothesis may lead to the formulation of new pathogenesis and new therapeutic approaches to IR. For example, an effective slimming pill will be assessed in future on the basis of the decrease of V/S and serum adipocytokines level rather than of body weight.

Introduction

Over the last two decades, the prevalence of overweight or obesity in the world has increased at an accelerating and alarming rate. Obesity is closely linked to a wide array of pathophysiologic consequences including insulin resistance (IR), type 2 diabetes mellitus (T2D), hypertension, hyperlipidemia and atherosclerosis. The association of obesity with T2D has been recognized for decades, and the major basis for this link is the ability of obesity to engender IR. But not all obese have IR or diabetes, not all fat depots contribute to this disease. Jean Vague et al. first discovered that fat distribution in the body is important for the progress of the disease. Thus, visceral fat in central or visceral obesity, mainly composed of omental and mesenteric fat and retroperitoneal fat, is more important in relation to IR than subcutaneous fat and the reduction in visceral fat can increase the sensitivity of insulin [1], [2], [3].

IR is a condition in which normal amounts of insulin fail to maintain normal blood glucose because of decreased responsiveness of muscle (glucose uptake), liver (inhibition of gluconeogenesis) and fat cells (inhibition of lipolysis). What is the mechanism linking obesity and IR? Circulating free fatty acids (FFAs) derived from adipocytes are elevated in many IR states and have been suggested to be a main underlying mechanism of IR in obesity-associated T2D [4]. However, adipose tissue being an active endocrine organ, compelling evidence demonstrates that several adipocyte-derived cytokines or hormones called adipocytokines are also involved in obesity-induced IR. Also, since visceral fat attracts more and more attention,in this article we focus on the contributions of visceral fat to IR and diabetes based on adipocytokines and fat depot distribution during the development of IR.

Section snippets

The role of adipocytokines in obesity

The adipocyte is unique among cells in that one “organelle”, the lipid droplet, encompasses greater than 95% of the entire cell body. It is now clear that the adipocyte has additional roles with the remaining 5% of its cellular mass. The significance of adipose tissue as an endocrine organ first surfaced in 1995 with the groundbreaking discovery of leptin [5]. Since then, a group of adipocyte-derived cytokines or hormones with different tissue distributions (adipocytokines) highly expressed in

Fat depot distribution in obesity

The classification scheme for obesity should include both central or (visceral obesity) and pheripheral obesity (called gynecoid or gluteofemoral obesity).

Central obesity is mainly composed of omental fat, mesenteric fat and retroperitoneal fat and peripheral obesity is mostly composed of subcutaneous fat. Compared with subcutaneous adipose tissue, human omental adipocytes display approximately twofold higher glucose uptake rate, and this could be explained by a higher glucose transporter type

Hypothesis and discussion

As for the mechanism linking obesity and IR, FFAs role is preferentially concidered because it has ever been suggested to be a main underlying cause of IR. In obesity, FFAs released from visceral fat to the liver via portal vein are more than those released from subcutaneous fat [37], which could decrease the sensitivity of insulin in the liver and exert dysfunction in the liver via several mechanisms, including stimulation of gluconeogenesis and/or fatty acid oxidation [38]. So FFAs have been

Conflict of interest statement

We declare that we have no financial and personal relationship with other people or organizations that can inappropriately influence our manuscript.

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