Determination of β3-Adrenoceptor Mediated Lipolysis in Human Fat Cells

The existence and relative importance of β₃-adrenoceptors in man is still controversial. The aim of the present study was 1) to find further evidence for the existence of functional β₃-adrenoceptors in human fat, and 2) to investigate factors that may influence this β₃-adrenoceptor function. Fifty individuals were examined. Lipolysis mediated by the selective β₃-adrenoceptor agonist CGP 12177 in omental fat cells correlated with the response in subcutaneous fat cells. However, lipolysis was more pronounced in omental as compared to subcutaneous adipocytes, the intrinsic activity for CGP 12177 was 41% and 33%, respectively, while dobutamine, terbutaline and norepinephrine were full agonists. Both the lipolytic response and the sensitivity to CGP 12177 correlated with the effects of norepinephrine in the omental fat cells (r²= 0. 68 and 0. 50, respectively, p=0. 0001). The β₂-adrenoceptor mediated lipolytic response did also correlate with the responses induced by β₁- and β₂-agonists and by postreceptor acting agents. The antagonistic properties (pA₂) of the β-adrenoceptor subtypes were also investigated. The pA₂ for the selective β₁- and β₂-adrenoceptor antagonists versus CGP 12177-induced lipolysis were 2 to 3 log units lower than those for the β₁-antagonist versus dobutamine or for the β₂-antagonist versus terbutaline. Furthermore, bupranolol had a significantly better antagonistic effect (pA₂ 7. 17, p<0. 001) on the CGP 12177-induced lipolysis than had the β₁- and β₂-adrenoceptor antagonists (pA₂ 6. 26 and 6. 05, respectively). These data clearly support the existence of a third human β-adrenoceptor. Several factors may contribute to the contradictory β₃-adrenoceptor results in man. The sensitivity of the different lipolytic systems vary considerably. Omental fat cells are preferable to subcutaneous cells for β₃-adrenoceptor studies in man. The β₃-responses are more attenuated in isolated fat cell preparations than in tissue fragments. Furthermore, as the β₃-adrenoceptor activity correlates to the norepinephrine activity, more pronounced effects will be expected in catecholamine sensitive subjects. At present, the number of tools available for β₃-adrenoceptor studies are limited, and the receptor is hard to study, why it is essential to perform β₃-adrenoceptor studies under optimal conditions in order to obtain conclusive effects.     

Knockdown of KLF9 promotes the differentiation of both intramuscular and subcutaneous preadipocytes in goat

ABSTRACT

KLF9 is reported to promote adipocyte differentiation in 3T3-L1 cells and pigs. However, the roles of KLF9 in adipocytes differentiation of goat remain unknown. In this study, the expression profiles of KLF9 were different between subcutaneous and intramuscular preadipocytes of goat during differentiation process. After silencing KLF9 gene, the lipid droplets were increased in both two types of adipocytes. In subcutaneous preadipocyte with silencing KLF9, the expressions of C/EBPβ, PPARγ, LPL, KLF1-2, KLF5, and KLF17 genes were up-regulated, while KLF12, KLF4, and KLF13 genes were down-regulated in expression level. In intramuscular preadipocyte, aP2, C/EBPα, KLF2-3, KLF5, and KLF7 gene were up-regulated, and Pref-1 gene was down-regulated. In addition, the binding sites of KLF9 existed in the promoters of aP2, C/EBPα, C/EBPβ, LPL and Pref-1. Taken together, KLF9 play a negative role in the differentiation of both intramuscular and subcutaneous preadipocytes in goats, but the functional mechanism may be different.     

Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: Adipose depot specificity and gender dimorphism

Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.     

Quantitation and Localization of Regional Body Fat Distribution - A Comparison Between Magnetic Resonance Imaging and Somatometry

The emerging concept that various fat compartments are metabolically active and play separate and decisive roles in the pathogenesis of coronary atherosclerosis, hypertension, insulin resistance, diabetes and stroke, has given obesity research a new direction. Of particular interest is the relative amount of intra-abdominal fat thought to be responsible for the metabolic complications. We studied the precise fat distribution and its correlations with the metabolic parameters in 44 non-human primates (Macaca fascicularis). Intra-abdominal, subcutaneous, and total abdominal fat (IAF, SAF, TAF) were assessed by magnetic resonance imaging (MRI) and somatometry. Quantitative computer analyses of abdominal MRI scans revealed predominant IAF distribution. Box plot analysis of IAF and SAF revealed wide diversity in the amounts of fat, especially in monkeys with body mass index (BMI) <30 kg/m². Primates with similar BMI in each quartile revealed an extensive heterogeneity in IAF as well as SAF. Numerous significant correlations within site-specific somatometric measurements as well as within the MRI determinants of abdominal fat were seen. However, only body weight correlated with IAF and skinfolds could predict SAF. After adjusting for body weight, partial correlation analysis showed a significant correlation (P<0.05) between total cholesterol and IAF. Conclusion: MRI revealed considerable heterogeneity of IAF, SAF and TAF in a cohort of primates believed to be homogeneous by somatometric definition. Male cynomolgus monkeys appear to be a valuable model for a systematic evaluation of fat. Individuals with identical body weight and height may show a diverse pattern of fat distribution.