The Endocrine Function of Adipose Tissue: An Update

Tiziana Ronti; Graziana Lupattelli; Elmo Mannarino

Disclosures

Clin Endocrinol. 2006;64(4):355-365. 

In This Article

Summary and Introduction

Adipose tissue secretes bioactive peptides, termed 'adipokines', which act locally and distally through autocrine, paracrine and endocrine effects. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis, all of which are linked with cardiovascular disease. Enhanced activity of the tumour necrosis factor and interleukin 6 are involved in the development of obesity-related insulin resistance. Angiotensinogen has been implicated in hypertension and plasminogen activating inhibitor-1 (PAI-1) in impaired fibrinolysis. Other adipokines like adiponectin and leptin, at least in physiological concentrations, are insulin sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The role of resistin is less understood. It is implicated in insulin resistance in rats, but probably not in humans. Reducing adipose tissue mass, through weight loss in association with exercise, can lower TNF-α and IL-6 levels and increase adiponectin concentrations, whereas drugs such as thiazolinediones increase endogenous adiponectin production. In-depth understanding of the pathophysiology and molecular actions of adipokines may, in the coming years, lead to effective therapeutic strategies designed to protect against atherosclerosis in obese patients.

Marked central adiposity, one of the main characteristics of the insulin resistance syndrome and/or metabolic syndrome, is the basis of the portal/visceral hypothesis that states that increased adiposity, particularly in visceral depots, leads to greater free fatty acid (FFA) flux and inhibition of insulin action via Randle's effect in insulin-sensitive tissues.[1] Aberrantly high availability of nonesterified fatty acids reduces muscle use of glucose, strongly stimulates hepatic glucose and very low-density lipoprotein (VLDL) production and acutely potentiates glucose-stimulated insulin secretion. The longer-term lipotoxic effect of fatty acids on the pancreatic β-cell may also be part of the link between obesity, insulin resistance and development of type 2 diabetes.

As recent findings do not entirely support the portal-visceral hypothesis, the theories of the ectopic fat storage syndrome[2] and the endocrine paradigm[3] have been developed to explain the links between adiposity and disease.

Three lines of evidence support the ectopic fat storage syndrome. First, in mice and humans, failure to develop adequate adipose tissue mass, also termed lipodystrophy, results in severe insulin resistance and diabetes, which might be consequent to ectopic lipid storage in the liver, skeletal muscle and pancreatic insulin-secreting beta cell. Second, most obese patients shunt lipid into keletal muscle, liver, and probably beta cells and, as demonstrated by several studies, the degree of lipid infiltration closely correlates with insulin resistance. Third, increased fat cell size is associated with insulin resistance and diabetes. Large fat cells may underlie the failure of the adipose tissue mass to expand and accommodate a high energy influx. Altogether, these three observations support the acquired lipodystrophy hypothesis as the link between adiposity and insulin resistance.[2]

The endocrine paradigm was developed at the same time as the hypothesis of the ectopic fat storage syndrome. Adipose tissue was traditionally considered an energy storage organ, but over the last decade, it has emerged as an endocrine organ. It is now recognized that adipose tissue produces multiple bioactive peptides, termed 'adipokines', which not only influence adipocyte function in an autocrine and paracrine fashion but also affect more than one metabolic pathway through the bloodstream.[3]

The concept of white adipose tissue as an endocrine organ originated in 1995 with the discovery of leptin and its wide-ranging biological functions.[4] To maintain normal body functions, each adipocyte secretes diverse cytokines and bioactive substances into the surrounding environment. Although each adipocyte produces a small quantity of adipocytokines, as adipose tissue is the largest organ in the human body, their total amount impacts on body functions. Furthermore, as adipose tissue is supplied by abundant blood stream adipocytokines released from adipocytes pour into the systemic circulation.

So far, many adipokines have been identified ( Table 1 ). They all integrate in a communications network with other tissues and organs such as the skeletal muscle, adrenal cortex, brain and sympathetic nervous system and participate in appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis ( Table 2 ).

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