White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPARγ in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.

. Indispensable role of mitochondrial UCP1 for antiobesity effect of ␤ 3-adrenergic stimulation. Am J Physiol Endocrinol Metab 290: E1014 -E1021, 2006. First published December 20, 2005 doi:10.1152/ajpendo.00105.2005.-Mitochondrial uncoupling protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy expenditure and adiposity. However, UCP1 knockout (KO) mice were reported to be cold intolerant but unexpectedly did not get obese even after hyperphagia, implying that UCP1 may not be involved in the regulation of adiposity. Treatment of obese animals with ␤ 3-adrenergic agonists is known to increase lipid mobilization, induce UCP1, and, finally, reduce body fat content. To obtain direct evidence for the role of UCP1 in the anti-obesity effect of ␤ 3-adrenergic stimulation, in the present study, UCP1-KO and wild-type (WT) mice were fed on cafeteria diets for 8 wk and then given a ␤ 3-adrenergic agonist, CL-316,243 (CL), or saline for 2 wk. A single injection of CL increased whole body oxygen consumption and brown fat temperature in WT mice but not in KO mice, and it elicited almost the same plasma free fatty acid response in WT and KO mice. WT and KO mice increased similarly their body and white fat pad weights on cafeteria diets compared with those on laboratory chow. Daily treatment with CL resulted in a marked reduction of white fat pad weight and the size of adipocytes in WT mice, but not in KO mice. Compared with WT mice, KO mice expressed increased levels of UCP2 in brown fat but decreased levels in white fat and comparable levels of UCP3. It was concluded that the anti-obesity effect of ␤ 3-adrenergic stimulation is largely attributable to UCP1, but less to UCP2 and UCP3, and thereby to UCP1-dependent degradation of fatty acids released from white adipose tissue.uncoupling protein-1; adiposity; CL-316,243; energy expenditure; hyperphagia UNCOUPLING PROTEIN (UCP) IS A MOLECULE, as its name suggests, that uncouples mitochondrial oxidative phosphorylation by bypassing the electrochemical gradient across the inner membrane from the F1-ATPase and thereby dissipates energy as heat. Among several isoforms of the UCP family so far reported in mammals, UCP1 is the only one whose physiological importance has been firmly established; that is, UCP1 is present exclusively in brown adipose tissue (BAT), an organ specified for nonshivering thermogenesis during cold acclimation, arousal from hibernation, and recovery from anesthetic hypothermia (2). UCP1 has also been proposed to be involved in diet-induced thermogenesis, as well as cold-induced nonshivering thermogenesis, and play a significant role in the control of energy expenditure and whole body energy balance. This is supported by the observations, for example, that spontaneous overfeeding of highly palatable diets and/or high-fat diets gives rise to increased energy expenditure (oxygen consumption) in association with BAT hyperplasia and increased UCP1 c...

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ABSTRACT. Adiponectin is an adipokine that is specifically expressed in adipose tissues, directly sensitizes the body to insulin via specific receptors and its decreased plasma concentration is responsible for insulin resistance in obese humans. Diabetes is an important problem also in veterinary medicine, and feline diabetes is very similar to human type 2 diabetes, in which obesity is an important risk factor. In the present study, We obtained cDNA clones corresponding to feline adiponectin and adiponectin receptor 1 (AD-R1), whose nucleotide and deduced amino acid sequences were highly identical to those of other species, especially, the extra-cellular domain of feline AD-R1 was almost identical to that of human AD-R1. Adiponectin mRNA was exclusively detected in the adipose tissue, but AD-R1 was in all tissues tested in this study. Next, plasma samples were collected from 22 cats visiting veterinary practices. They were divided to 2 groups based on a five-point scale body condition score (BCS), such as normal group (BCS ranged from 2.5 through 3.5) and obese group (BCS ranged from 4.0 through 5.0). Plasma adiponectin in obese cats (7.2 ± 1.5 µg/ml) was significantly lower than that of normal cats (18.0 ± 3.2 µg/ml). These results suggest that adiponectin may be responsible for insulin function also in the cat, and it can be a target molecule for treatment of obesity and diabetes in cats. KEY WORDS: adiponectin, AD-R1, diabetes, feline, obesity.J. Vet. Med. Sci. 71(2): 189-194, 2009 The adipose tissue has long been thought to be the site for energy storage and a target of various hormones, which regulate energy metabolism. However, recent studies have revealed that the adipose tissue itself is an active endocrine organ, which produces and secretes many polypeptides, collectively called as adipokines, such as leptin, tumor necrosis factor (TNF)-α, plasminogen activator inhibitor-1 and resistin [1]. For example, leptin is secreted from adipose tissues in response to changes in energy balance, acts on hypothalamus to regulate food intake and the neuroendocrine mechanisms controlling energy expenditure [4]. Adiponectin is an adipokine found at almost three-order higher concentrations in blood than other adipokines [6], and its plasma concentration decreases with body fat accumulation [2]. It is now recognized as one of the key adipokines responsible for obesity-associated atherosclerosis and insulin resistance (diabetes mellitus of type 2) in humans [2,3]. Recently, two isoforms of adiponectin receptors (AD-R1 and AD-R2) were determined by expression cloning, and they showed different tissue distributions. AD-R1 is expressed ubiquitously in most organs including skeletal muscle, and thought to be important to keep the insulin sensitivity. In obese people, it is suggested that reduced adiponectin induces insulin resistance, and it is the major pathophysiological factor of diabetes [12,21].In companion animal medicine, as in human medicine, obesity and diabetes mellitus are the most common nutritional/endocrinol...

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