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C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes.

ABSTRACT: Despite the prevalence of insulin resistance and type 2 diabetes mellitus, their underlying mechanisms remain incompletely understood. Many secreted endocrine factors and the intertissue cross-talk they mediate are known to be dysregulated in type 2 diabetes mellitus. Here, we describe CTRP12, a novel adipokine with anti-diabetic actions. The mRNA and circulating levels of CTRP12 were decreased in a mouse model of obesity, but its expression in adipocytes was increased by the anti-diabetic drug rosiglitazone. A modest rise in circulating levels of CTRP12 by recombinant protein administration was sufficient to lower blood glucose in wild-type, leptin-deficient ob/ob, and diet-induced obese mice. A short term elevation of serum CTRP12 by adenovirus-mediated expression improved glucose tolerance and insulin sensitivity, normalized hyperglycemia and hyperinsulinemia, and lowered postprandial insulin resistance in obese and diabetic mice. CTRP12 improves insulin sensitivity in part by enhancing insulin signaling in the liver and adipose tissue. Further, CTRP12 also acts in an insulin-independent manner; in cultured hepatocytes and adipocytes, CTRP12 directly activated the PI3K-Akt signaling pathway to suppress gluconeogenesis and promote glucose uptake, respectively. Collectively, these data establish CTRP12 as a novel metabolic regulator linking adipose tissue to whole body glucose homeostasis through insulin-dependent and independent mechanisms.

SUBMITTER: Wei Z

PROVIDER: S-EPMC3322967 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes.

Wei Zhikui Z Peterson Jonathan M JM Lei Xia X Cebotaru Liudmila L Wolfgang Michael J MJ Baldeviano G Christian GC Wong G William GW

The Journal of biological chemistry 20120124 13

Despite the prevalence of insulin resistance and type 2 diabetes mellitus, their underlying mechanisms remain incompletely understood. Many secreted endocrine factors and the intertissue cross-talk they mediate are known to be dysregulated in type 2 diabetes mellitus. Here, we describe CTRP12, a novel adipokine with anti-diabetic actions. The mRNA and circulating levels of CTRP12 were decreased in a mouse model of obesity, but its expression in adipocytes was increased by the anti-diabetic drug ...[more]

PMID: 22275362

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Project description:Background:C1q TNF related protein 3 (CTRP3) is a relatively novel hormonal factor primarily derived from adipose tissue and has anti-diabetic properties. To determine if CTRP3 could play a role in early childhood development, the purpose of this study was to establish the presence of CTRP3 in breast milk (BM) and to determine whether CTRP3 levels were correlated with pregravid obesity status of the mother. Methods:Breast milk was collected from breast-feeding mothers who had a pregravid body mass index (BMI) classification of normal weight (BMI 18-25 kg/m2, n = 23) or obese (BMI > 30 kg/m2, n = 14). Immunoprecipitation followed by immunoblot analysis confirmed the presence of CTRP3 in BM. The concentration of CTRP3 in BM samples was determined by ELISA. Additional bioactive components were also measured by commercially available assays: ghrelin, insulin, leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?), and glucose. Bioactive components in normal weight and obese mothers were compared using unpaired t-test (parametric) and Mann-Whitney U-test (non-parametric), as appropriate. Results:The primary findings of this study are that the adipokine CTRP3 is present in BM and CTRP3 levels are increased with pregravid obesity. Additionally, this study independently confirmed previous work that BM from obese mothers has a higher concentration of insulin and leptin. Further, no differences were observed in BM between obese and normal weight mothers in ghrelin, adiponectin, IL-6, TNF-?, or glucose levels. Conclusion:This study identified a novel factor in BM, CTRP3, and showed that BM CTRP3 levels higher in obese mothers. Because of the purported insulin sensitizing effect of CTRP3, it is possible that the elevated levels of CTRP3 in the BM of obese mothers may offset negative effects of elevated leptin and insulin levels in the BM of obese mothers. Future studies will need to be conducted to determine the relevance of CTRP3 in BM and to examine the presence of other adipose tissue-derived hormonal factors.

Dataset Information

C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes.

Publications

C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes.

Similar Datasets

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