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Adiposity and obesity are increasing in dogs. We have examined here the endocrine function of canine adipose tissue and the regulation of production of inflammation-related adipokines by dog adipocytes. Adiponectin, leptin, IL-6, MCP-1 and TNFalpha genes were expressed in the main adipose depots of dogs, but there were no major depot differences in mRNA levels. Each adipokine was expressed in canine adipocytes differentiated in culture and secreted into the medium (leptin undetected). IL-6, MCP-1 and TNFalpha were also expressed and secreted by preadipocytes; adiponectin and leptin were only expressed after adipocyte differentiation. The inflammatory mediators LPS and TNFalpha had major stimulatory effects on the expression and secretion of IL-6, MCP-1 and TNFalpha; there was a >5,000-fold increase in IL-6 mRNA level with LPS. IL-6 release into the medium was increased >50-fold over 24 h with LPS and TNFalpha, while MCP-1 release was increased 23- and 40-fold by TNFalpha and LPS, respectively. However, there was no effect, or small reductions, in adiponectin and leptin mRNA levels with the inflammatory mediators. Dexamethasone-stimulated leptin gene expression, had no effect on adiponectin expression, but decreased the expression and secretion of IL-6 and MCP-1. The PPARgamma agonist rosiglitazone stimulated both adiponectin and leptin expression and inhibited the expression of IL-6, MCP-1 and TNFalpha; MCP-1 secretion was reduced. These results demonstrate that canine adipocytes express and secrete key adipokines and show that adipocytes of this species are highly responsive to inflammatory mediators with the induction of major increases in the production of inflammation-related adipokines.

In subjects with obesity, diabetes and coronary artery disease, circulating levels of leptin increased while that of adiponectin is decreased. In this study we have investigated effects of physiological and pharmacological weight reduction on leptin and adiponectin mRNA expression. Wistar rats were fed either standard laboratory chow for 16 weeks (chow-fed) or given a fat-enriched, glucose-enriched diet (diet-fed) for 8 weeks. After 8 weeks, diet-fed group was subdivided into three subgroups, namely, an untreated obese, or were returned to chow diet, or treated with fenofibrate for further 8 week. After 16 weeks, compared with chow-fed group, diet-fed rats had significantly higher body weight, epididymal fat pad mass, and plasma levels of insulin, leptin, adiponectin, non-esterified fatty acids and triglycerides (P<0.001, for all). Moreover, untreated obese rats had significantly (P<0.01, for both) raised levels of Ob mRNA but reduced adiponectin mRNA levels in epididymal fat pads compared with chow-fed group. These changes were corrected by chronic removal of the high-energy diet and fenofibrate treatment. These findings indicate that physiological or pharmacological lowering of body weight together with circulating plasma lipids play a significant role in leptin and adiponectin synthesis and metabolism.

Objective: A great deal of attention has focused on the central role of alpha melanocyte-stimulating hormone (alpha-MSH) and its antagonism at the melanocortin-4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and alpha-MSH in humans. We aimed to determine whether circulating alpha-MSH and AgRP are responsive to long-term perturbations in energy balance, in a manner consistent with their central putative functions., Design and Measurements: Circulating alpha-MSH, AgRP and leptin were measured in both lean (n = 11) and obese (n = 18) male volunteers, some of whom (lean n = 11, obese n = 12) were then allocated one of two weight-loss dietary strategies to achieve about 5% weight loss. This was achieved by either total starvation (for 4-6 days) for rapid weight loss or a very low calorie diet (VLCD, 2.6 MJ/day) (11-12 days) for less rapid weight loss, in both the lean and obese volunteers., Results: At baseline, prior to any weight loss both plasma alpha-MSH (15.8 +/- 1.2 vs. 5.8 +/- 1.0 pmol/l +/- SEM; P < 0.001) and AgRP (49.4 +/- 2.4 vs. 10.1 +/- 0.9 pg/ml +/- SEM; P < 0.001) were elevated in obese subjects compared with lean. In both cases this correlated closely with fat mass (P < 0.001), percentage body fat (P < 0.001) and leptin (P < 0.05). Plasma AgRP increased significantly during a 6-day fast in lean individuals (11.1 +/- 1.6 vs. 21.6 +/- 3.1 pg/ml +/- SEM; P < 0.05) but not in the VLCD subjects or in the obese, while alpha-MSH was not affected by any changes in energy balance in either the lean or the obese volunteers., Conclusion: We show a difference in alpha-MSH and AgRP in lean and obese subjects that correlates closely with body fat at baseline. We demonstrate an increase in plasma AgRP during a 6-day fast in lean individuals that is coincident with a decrease in plasma leptin. This increase in AgRP was not due to weight loss per se as there was no change in AgRP as a result of the same weight loss in the VLCD intervention in lean individuals. The source of the increase in plasma AgRP and its physiological function in the periphery remains to be elucidated but we suggest that the dynamics of the change in plasma leptin may determine the elevation in fasting plasma AgRP in lean subjects.

A great deal of attention has focused on the central role of alpha melanocyte-stimulating hormone (α-MSH) and its antagonism at the melanocortin-4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and α-MSH in humans. We aimed to determine whether circulating α-MSH and AgRP are responsive to long-term perturbations in energy balance, in a manner consistent with their central putative functions. Circulating α-MSH, AgRP and leptin were measured in both lean ( n = 11) and obese ( n = 18) male volunteers, some of whom (lean n = 11, obese n = 12) were then allocated one of two weight-loss dietary strategies to achieve about 5% weight loss. This was achieved by either total starvation (for 4–6 days) for rapid weight loss or a very low calorie diet (VLCD, 2·6 MJ/day) (11–12 days) for less rapid weight loss, in both the lean and obese volunteers. At baseline, prior to any weight loss both plasma α-MSH (15·8 ± 1·2 vs. 5·8 ± 1·0 pmol/l ± SEM; P < 0·001) and AgRP (49·4 ± 2·4 vs. 10·1 ± 0·9 pg/ml ± SEM; P < 0·001) were elevated in obese subjects compared with lean. In both cases this correlated closely with fat mass ( P < 0·001), percentage body fat ( P < 0·001) and leptin ( P < 0·05). Plasma AgRP increased significantly during a 6-day fast in lean individuals (11·1 ± 1·6 vs. 21·6 ± 3·1 pg/ml ± SEM; P < 0·05) but not in the VLCD subjects or in the obese, while α-MSH was not affected by any changes in energy balance in either the lean or the obese volunteers. We show a difference in α-MSH and AgRP in lean and obese subjects that correlates closely with body fat at baseline. We demonstrate an increase in plasma AgRP during a 6-day fast in lean individuals that is coincident with a decrease in plasma leptin. This increase in AgRP was not due to weight loss per se as there was no change in AgRP as a result of the same weight loss in the VLCD intervention in lean individuals. The source of the increase in plasma AgRP and its physiological function in the periphery remains to be elucidated but we suggest that the dynamics of the change in plasma leptin may determine the elevation in fasting plasma AgRP in lean subjects. [ABSTRACT FROM AUTHOR]

Leptin is a 167-amino acid protein that is secreted from adipose cells and expressed in placental tissues. It is important nutritionally in the regulation of energy balance, but also has other functions such as a role in reproduction. To investigate the function of the leptin system in fetal development we examined, primarily by in-situ hybridization and immunohistochemistry, the expression (both mRNA and protein) of leptin and its receptor (including the signalling splice variant) in tissues from 11·5, 13·5, 16·5 and 18·5 d postcoitus murine fetuses and associated placentas. We detected leptin mRNA (at low levels) and protein predominantly in the cytotrophoblasts of the labyrinth part of the placenta, an area of nutrient exchange between the developing fetus and the placenta, and in the trophoblast giant cells situated in the junctional zone at the maternal interface. In addition, leptin was strongly expressed in the fetal cartilage–bone and at a lower level in the hair follicles, heart, and liver of the murine fetus at differing stages of development. The leptin receptor, including the signalling splice variant, was also identified in specific fetal tissues. The physiological importance of expression of both leptin and the leptin receptor (OB-R and OB-Rb) in the placenta remains to be determined. In addition, the high levels of expression of leptin and its receptor in discrete areas of the murine fetus suggest that leptin has a critical role in fetal development. [ABSTRACT FROM PUBLISHER]