AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity

Abstract

Adipose differentiation is accompanied by changes in cellular morphology, a dramatic accumulation of intracellular lipid and activation of a specific program of gene expression. Using an mRNA differential display technique, we have isolated a novel adipose cDNA, termed adipoQ. The adipoQ cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a collagenous region (Gly-X-Y repeats), and a globular domain. The globular domain of adipoQ shares significant homology with subunits of complement factor C1q, collagen ␣1(X), and the brainspecific factor cerebellin. The expression of adipoQ is highly specific to adipose tissue in both mouse and rat. Expression of adipoQ is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain adipoQ mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for adipoQ. Furthermore, the expression of adipoQ mRNA is significantly reduced in the adipose tissues from obese mice and humans. Whereas the biological function of this polypeptide is presently unknown, the tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue.Adipose tissue is highly specialized to play important roles in energy storage, fatty acid metabolism, and glucose homeostasis (1, 2). Adipocytes synthesize and store triglyceride in periods of nutritional abundance and mobilize the lipids in response to fasting (2, 3). Fat tissue is also involved in regulating blood glucose levels through the expression of the insulin responsive glucose transporter, Glu4 (4, 5). Fat and muscle, in fact, constitute the two major sites for insulin-regulated glucose uptake.At a molecular level, many genes involved in lipid metabolism and glucose homeostasis are prominently expressed in fat (1). These include fatty acid synthase (6), the fatty acid binding protein aP2 (7,8), lipoprotein lipase (9), phosphoenolpyruvate carboxykinase (10), malic enzyme (11), glyceraldehyde-3-phosphate dehydrogenase (12), and Glut4 (4). Receptors for lipogenic or lipolytic hormones such as insulin (13, 14), insulin-like growth factor 1 (15), and adrenergic compounds (16,17) are also expressed in adipocytes. In addition to these genes that clearly participate in the metabolic functions of adipose tissue, a group of genes that function in extracellular signaling have also been identified in fat. A prototype of these molecules is insulin-like growth factor 1, which is expressed in many tissues during development and plays an important role in cell proliferation (18). In adipocytes, however, insulin-like growth factor 1 is found to stimulate cell differentiation (19). More interestingly, insulin-like growth factor 1 is synthesized by preadipocytes in response to growth hormone stimulation (20), thus potentially functioning in an autocrine or paracrine fashion to promote adipogenesis during development. Another si...

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

“…The best‐characterized effects of adiponectin include enhanced insulin sensitivity, anti‐inflammatory properties, and inhibition of the development of atherosclerosis 38. In contrast to leptin, it has been shown that an increase in the fat mass decreases the circulating adiponectin level, whereas weight loss increases the adiponectin concentrations in obese human, primates, and rodents 39, 40. Similarly, adiponectin might be inversely related to adiposity in obese dogs,41 although there is a controversy about the inverse relationship 30, 42.…”

Adipose Tissue as an Endocrine Organ

“…Adiponectin was independently characterized in 1995 and 1996 by four groups using different methods, hence its alternative names of apM1 (adipose most abundant gene transcript 1), Acrp30 (adipocyte complement-related protein of 30 kDa), adipoQ, and GBP28 (gelatin binding protein of 28 kDa) (43)(44)(45)(46). Adiponectin is highly and specifically expressed in differentiated adipocytes and circulates at high levels in the bloodstream (47).…”

“…Adiponectin is an approximately 30-kDa polypeptide containing an Nterminal signal sequence, a variable domain, a collagen-like domain, and a C-terminal globular domain (43)(44)(45)(46). It shares strong sequence homology with type VIII and X collagen and complement component C1q (43)(44)(45)(46). Interestingly, the tertiary structure of the globular domain bears a striking similarity to TNF␣, despite a lack of homology in primary sequence (47).…”

Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

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