No abstract

Background: Chemotactic cytokines, referred to as chemokines, play an important role in leukocyte trafficking. The circulating levels of chemokines have been shown to increase in inflammatory processes including obesity-related pathologies (e.g. atherosclerosis and diabetes). However, little is currently known about the relationship between chemokines and human obesity. In the present study, we investigated the circulating levels of selected chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1a (MIP-1a), leukotactin-1, interleukin-8 (IL-8)) and the association between the chemokine levels and obesity-related parameters: body mass index (BMI), waist circumference, fasting glucose and insulin levels, lipids profile, and the level of C-reactive protein (CRP). Methods: A total of 100 subjects, 50 obese (BMIX25 kg/m 2 ) and 50 who were not obese (BMIo25 kg/m 2 ) participated in the present study. The levels of chemokines and CRP were measured in a fasting state serum by sandwich enzyme-linked immunosorbent assay. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and insulin levels were measured by enzymatic analysis and immunoassay. Results: The circulating levels of MCP-1 and IL-8 in the serum were significantly (Po0.05) higher in obese subjects (BMI430 kg/ m 2 ) compared with those of nonobese controls (BMIo25 kg/m 2 ). The levels of CRP were positively correlated with BMI (Po0.001) or waist circumference (Po0.0001). The levels of MCP-1 and IL-8 were positively related to BMI (MCP-1, Po0.02; IL-8, Po0.01) and/or waist circumference (MCP-1, Po0.009; IL-8, Po0.03). The levels of MCP-1 were positively related to the levels of CRP (Po0.007) or interleukin-6 (IL-6) (Po0.0001), and negatively related to the levels of HDL-cholesterol (Po0.01). Homeostasis model assessment (HOMA) score was positively related to the levels of MCP-1 (Po0.02) or IL-8 (Po0.03) in obese subject. Discussion: Our data demonstrated that the circulating levels of MCP-1 and IL-8 are related to obesity-related parameters such as BMI, waist circumference, CRP, IL-6, HOMA and HDL-cholesterol. These findings suggest that the circulating MCP-1 and/or IL-8 may be a potential candidate linking obesity with obesity-related metabolic complications such as atherosclerosis and diabetes.

A well balanced body energy budget controlled by limitation of calorie uptake and͞or increment of energy expenditure, which is typically achieved by proper physical exercise, is most effective against obesity and diabetes mellitus. Recently, peroxisome proliferator-activated receptor (PPAR) ␥, a member of the nuclear receptor, and its cofactors have been shown to be involved in lipid metabolism and in the control of energy expenditure. Here we show that PPAR␥ coactivator 1 (PGC-1) ␤ functions as ERRL1 (for ERR ligand 1), which can bind and activate orphan ERRs (estrogen receptor-related receptors) in vitro. Consistently, PGC-1␤͞ERRL1 transgenic mice exhibit increased expression of the medium-chain acyl CoA dehydrogenase, a known ERR target and a pivotal enzyme of mitochondrial ␤-oxidation in skeletal muscle. As a result, the PGC-1␤͞ERRL1 mice show a state similar to an athlete; namely, the mice are hyperphagic and of elevated energy expenditure and are resistant to obesity induced by a high-fat diet or by a genetic abnormality. These results demonstrate that PGC-1␤͞ERRL1 can function as a protein ligand of ERR, and that its level contributes to the control of energy balance in vivo, and provide a strategy for developing novel antiobesity drugs.

The oxytocin receptor has been suggested to be involved in energy metabolism, such as food intake and energy consumption. Here, we demonstrate that oxytocin receptor-deficient (Oxtr-/-) male mice exhibited late-onset obesity with increases in abdominal fat pads and fasting plasma triglycerides. Daily food intake and spontaneous motor activity of Oxtr-/- mice were not significantly different as compared with wild-type mice. In contrast, brown adipose tissue in Oxtr-/- mice contained large lipid droplets and cold-induced thermogenesis was impaired. This study demonstrates that oxytocin receptor plays essential roles in the regulation of energy homeostasis.