Recent studies suggest that thermogenesis in brown adipose tissue has an important role in the regulation of energy balance. Thermogenesis is effected by noradrenaline released from sympathetic nerve endings; the noradrenaline stimulates beta-adrenoceptors, causing lipolysis, and the released fatty acids then promote the uncoupling of oxidative phosphorylation from electron transport. It has been widely accepted that mammalian beta-adrenoceptors exist as two subtypes, beta 1 and beta 2, and rat brown adipocyte beta-adrenoceptors have been classed as beta 1 or as a mixed beta 1/beta 2 population. The beta 1 subtype predominates in atria, whereas the beta 2 subtype predominates in trachea. However, we have now found a novel group of beta-adrenoceptor agonists that selectively stimulate lipolysis in brown adipocytes. In contrast, isoprenaline, fenoterol and salbutamol are less potent as stimulants of lipolysis than as stimulants of atrial rate or tracheal relaxation. Therefore, beta-adrenoceptors in rat brown adipocytes are of neither the beta 1 nor beta 2 subtypes. Compounds that selectively stimulate brown adipocyte beta-adrenoceptors should have potential as thermogenic anti-obesity agents and this has been demonstrated with BRL 26830A , BRL 33725A and BRL 35135A .

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a b s t r a c t GPR41 is reportedly expressed in murine adipose tissue and mediates short chain fatty acid (SCFA)-stimulated leptin secretion by activating Ga i . Here, we agree with a contradictory report in finding no expression of GPR41 in murine adipose tissue. Nevertheless, in the presence of adenosine deaminase to minimise Ga i signalling via the adenosine A1 receptor, SCFA stimulated leptin secretion by adipocytes from wild-type but not GPR41 knockout mice. Expression of GPR43 was reduced in GPR41 knockout mice. Acetate but not butyrate stimulated leptin secretion in wild-type mesenteric adipocytes, consistent with mediation of the response by GPR43 rather than GPR41. Pertussis toxin prevented stimulation of leptin secretion by propionate in epididymal adipocytes, implicating Ga i signalling mediated by GPR43 in SCFA-stimulated leptin secretion.

The adipocyte hormone leptin activates signal transducer and activator of transcription 3 (STAT3) in the hypothalamus, mediating increased satiety and increased energy expenditure. To date, leptin-mediated activation of the STAT pathway in vivo has not been established in tissues other than hypothalamus. We now describe leptin receptor expression and in vivo signaling in discrete regions of the mouse gastrointestinal tract. Expression of the functional isoform leptin receptor (OB-Rb) is restricted to the jejunum and is readily detected by RT-PCR in isolated enterocytes from this site. Intravenous injection of leptin rapidly induced nuclear STAT5 DNA binding activity in jejunum of ؉/؉ and obese (ob/ob) mice but had no effect in the diabetic (db/ db) mouse that lacks the OB-Rb isoform. In addition, an induction of the immediate-early gene c-fos is observed in jejunum in vivo. Leptin-mediated induction of a number of immediate-early genes and activation of STAT3 and STAT5 in a human model of small intestine epithelium, CACO-2 cells, corroborate this effect. Furthermore, intravenous leptin administration caused a significant 2-fold reduction in the apolipoprotein AIV transcript levels in jejunum 90 min after a fat load. Our results suggest that the epithelium of jejunum is a direct target of leptin action, and this activity is dependent on the presence of OB-Rb. Lack of leptin or resistance to leptin action in this site may contribute to obesity and its related syndromes by directly affecting lipid handling.Obesity is the result of an imbalance in energy intake and expenditure. This condition is associated with a number of pathological conditions, including non-insulin-dependent diabetes, cardiovascular disease, hypertension, and insulin resistance, that are characterized typically by inappropriately elevated plasma levels of insulin, glucose, triglycerides, and lipoproteins. Homeostatic mechanisms that coordinate the storage and use of energy from the constituents of a meal are disturbed in this condition, leading to exaggerated adipose tissue deposition. As a result there is a commensurate increase in the synthesis and secretion of the adipose tissue hormone leptin, a recently discovered factor that acts on the hypothalamus to inhibit food intake and increase energy expenditure (1). The importance of leptin in the regulation of energy balance is accentuated by the profound early onset obesity, hyperinsulinemia, and insulin resistance exhibited by obese (ob/ob) mice, the genetic strain that lacks functional leptin (1). Upon administration of the recombinant hormone to these mice, they, and to a lesser extent their lean littermates, exhibit a marked reduction in weight and a lowering of plasma insulin and glucose concentrations (2, 3). A phenotypically similar strain, the diabetic (db/db) mouse, has a defect in the leptin receptor and has been shown to be unresponsive to leptin in a number of in vivo and in vitro experiments (4 -8). Although seemingly rare, examples of leptin deficiency in humans demonstrate that th...

Here we demonstrate for the first time that plasma chemerin levels are significantly heritable and identified a novel role for chemerin as a stimulator of angiogenesis.