Physiological and pathological roles of mast cells in adipose tissue

Mast cells are important cells for the innate immunity that reside in tissues including adipose tissue and are involved in various physiological and pathological processes by producing a range of biological mediators. Adipose tissue not only acts as an energy depot and regulator of energy homeostasis that can deposit excess energy and dissipate energy through heat, but also is an active endocrine organ capable of producing hormones and adipokines. The dysfunction of adipose tissue is highly correlated with metabolic disorders, such as obesity, type 2 diabetes mellitus and so on. This review focuses on the physiological and pathological roles of mast cells in adipose tissue.     

Advance in study of batokines

Brown adipose tissue is a type of adipose tissue and is present in all mammals. It is not only the main site for adaptive thermogenesis in vivo, but also secretes and releases many cytokines in the form of endocrine to regulate a variety of metabolic processes and prevent and treat obesity and metabolic diseases. Therefore, identification of the types and effects of brown adipocytokines (batokines) may be crucial for the treatment of a variety of obesity-related metabolic diseases. Based on the latest research progress, batokines and their functions are reviewed.     

Effect of hypothalamic PVN exogenous orexin-A on food intake in obese rats and regulation by NPY receptor signaling pathway

AIM:To investigate whether neuropeptide Y (NPY) receptor signaling pathway is involved in the regulation of orexin-A on food intake and glucose-sensitive (GS) neuronal excitability in the hypothalamic paraventricular nucleus (PVN) of diet-induced obese (DIO) rats. METHODS:Fluorescence immunohistochemistry experiment was used to observe the expression of orexin-A receptor (orexin receptor 1, OX1R) and NPY receptor Y5 (NPY-5R) in the PVN. The effect of orexin-A on the excitability of GS neurons in PVN was observed by single cell discharge recording. The cannula was implanted into the PVN of SD rats and DIO rats. The orexin-A, OX1R antagonist SB-334867 and NPY-5R antagonist CGP-71683 were injected through the cannula to observe the 0~2 h and 0~4 h food intake of the rats. RESULTS:The expression of OX1R and NPY-5R in the PVN of DIO rats was significantly higher than that in the SD rats. Orexin-A inhibited glucose-inhibited (GI) neurons and excited glucose-excited (GE) neurons in the PVN. However, the effects of orexin-A on GS neurons were partially blocked by the NPY-5R antagonist CGP-71683. Compared with the SD rats, orexin-A had more pronounced excitatory and inhibitory effects on PVN GS neurons in the DIO rats. Injection of orexin-A in the PVN increased food intake in the SD rats and DIO rats. However, the orexin-A-induced feeding was partially blocked by the NPY-5R antagonist CGP-71683. The effect of orexin-A on feeding was stronger in the DIO rats than that in the SD rats. CONCLUSION:The hypothalamic PVN orexin-A regulates food intake and GS neuronal excitability mainly through the OX1R signaling pathway, and NPY-5R signaling is also involved in this process, in which the regulatory effect on DIO rats is more sensitive.     

Effect of GLP-1 receptor agonist on lipolysis in adipose tissue of obese mice and its underlying mechanism

AIM: To investigate the effects of glucagon-like peptide-1(GLP-1) receptor agonist exendin-4 on white adipose tissue (WAT) and the underlying mechanisms. METHODS: Male C57BL/6J mice (8 weeks) were challenged by high-fat diet for 12 weeks, and were randomly divided into saline group and exendin-4 group. The mRNA expression of sirtuin 1(SIRT1), adipose triglyceride lipase (ATGL), TNF-α and adiponectin of WAT was detected by real-time PCR. 3T3-L1 adipocytes or mouse embryonic fibroblasts cells were treated with exendin-4 for 24 h. The protein levels of SIRT1, ATGL and hormone-sensitive lipase (HSL) were determined by Western blot.RESULTS: Exendin-4 significantly decreased epididymal fat weight, fasting blood glucose and serum triglyceride levels (P<0.05), and reduced body weight and serum TNF-α level. The mRNA expression of SIRT1, ATGL and adiponectin in WAT was all significantly up-regulated by exendin-4, which were contrary to the down-regulation of TNF-α mRNA expression (P<0.05). Exendin-4 promoted the protein expression of SIRT1, ATGL, and HSL in 3T3-L1 adipocytes in a dose-dependent manner. Less lipid droplets with up-regulation of lipolytic protein expression were observed when combined with SIRT1 agonist treatment, which were suppressed by SIRT1 inhibitor. Deletion of SIRT1 led to larger adipocytes with more lipid droplets, and the effect of exendin-4 on the lipolysis disappeared when SIRT1 was deficient.CONCLUSION: Exendin-4 promotes lipolysis in WAT of obese mice via activation of SIRT1.     

Dietary energy restriction and successful weight loss in obese client-owned dogs

BACKGROUND: Obesity is the most common nutritional disease in dogs. Although weight loss by dietary caloric energy restriction is successful in experimental studies, there is limited information on success of such programs in client-owned dogs who are obese. Further, no information currently exists on the changes in body composition during weight loss in clinical cases. HYPOTHESIS: Key determinants of outcome of weight loss, including energy allocation and body composition, are influenced by both individual and weight program factors. ANIMALS: Nineteen client-owned dogs with naturally occurring obesity. METHODS: In this prospective clinical study, body composition was quantified by dual-energy X-ray absorptiometry before and after weight loss on an individually tailored program that incorporated a high-protein and moderate-fiber diet. RESULTS: Mean percentage weight loss was 18% (range, 6-29%), and mean rate of weight loss was 0.85% per week (range, 0.35-1.56%). Mean energy allocation required to achieve weight loss was 60% of maintenance energy requirement at target weight (MERTW) (range, 50-82%). Significant dietary noncompliance was reported (mean, 1.0% MERTW; range, 0.0-9.5%). The mean composition of tissue lost was 84: 15:1 (fat : lean : bone mineral content [BMC]). Lean tissue loss was positively associated with overall percentage of weight loss (Pearson correlation coefficient [Rp] = 0.591, P = .008), whereas BMC loss was greater in retrievers compared with other breeds (1.9% +/- 1.16% versus 0.8% +/- 0.44%; P = .008). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical study demonstrated body composition changes during weight loss in dogs. Conventional programs produced safe weight loss, but marked energy restriction was required and the rate of loss was slower than in experimental studies.     

Moderate quantity of lard mixed with sunflower oil attenuate lipid accumulation in mice

Lard, a fat rich in saturated fatty acids (SFAs), is regarded as a risk factor for metabolic diseases. In the present study, effect of different lard blended with sunflower oil diets on lipid accumulation in adipose tissue, liver, and serum by mouse model was researched. Body weight, body fat percentage, cross-sectional area of adipocytes, liver triglycerides (TGs), and oil red stained area in mice liver of lard blend sunflower oil (L-SFO) group were significantly lower than those of sunflower oil (SFO) group, whereas no significant differences were observed between mice of lard and L-SFO groups. Serum TG and free fatty acid levels were significantly lower in L-SFO group than in other two groups. Furthermore, data showed that sunflower oil decreased contents of hormone-sensitive lipase and carnitine palmitoyl transferase 1 (CPT-1) and increased fatty acid synthase activity in liver tissue. A mixture of lard and sunflower oil rather than only sunflower oil or lard might promote body fat loss and reduce lipid accumulation in adipose tissue, serum, and liver by promoting hydrolysis of TG, increasing β-oxidation of fatty acids. These data suggested that mixing lard and vegetable oil (e.g. sunflower oil) for cooking, or alternate using lard and vegetable oil could be beneficial for reducing body fat.     

Regulation of Insulin Action by Diet and Exercise

The regulation of the cellular actions of the hormone insulin is essential to the maintenance of macronutrient metabolism, body weight regulation, and a surprisingly diverse range of other integrative physiologic functions. Because of the diverse targets of insulin action, any dysfunction in insulin is likely to have systemic consequences. Although type 1 and type 2 diabetes are the most obvious clinical consequences of impaired insulin synthesis and insulin action, respectively, there are also subclinical disorders that attend defects in the function of insulin. In humans and horses, the “metabolic syndrome” is characterized by a cluster of metabolic sequelae that arise as a result of insulin resistance. Importantly, both diet and exercise can regulate insulin action and can thus be leveraged as treatment tools to prevent and treat the metabolic syndrome. The aim of this review is to characterize the integrative biology of insulin action and to describe the role of diet and exercise in regulating tissue responsiveness to insulin.