Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K. et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7, 941-946

Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Nature Medicine (Impact Factor: 27.36). 09/2001; 7(8):941-6. DOI: 10.1038/90984
Source: PubMed


Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.

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    • "Adiponectin is abundantly present in human plasma, the level of which is reduced in obesity, diabetes mellitus and insulin resistance [30]. Furthermore, the adipokine could increase insulin sensitivity [31]. In the present study, 17b-estradiol but not progesterone dramatically suppressed the level of adiponectin, which seems to be in the line of the resistin finding because the decrease in adiponectin concentration could be associated with insulin resistance and other related disorders [32]. "
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    ABSTRACT: Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10-8-10-7M), progesterone (10-6-10-5M), the Rho-kinase inhibitor, Y-27632 (10-5M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation.
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    • "In concert, these adipokines are believed to adapt metabolic fluxes to the amount of stored energy. Dysregulation of this network is a critical factor in the deterioration of insulin sensitivity [4] [6]. "
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    ABSTRACT: We aimed to systematically review available literature linking adipokines to gestational diabetes mellitus (GDM) for a comprehensive understanding of the roles of adipokines in the development of GDM. We searched PubMed/MEDLINE and EMBASE databases for published studies on adipokines and GDM through October 21, 2014. We included articles if they had a prospective study design (i.e., blood samples for adipokines measurement were collected before GDM diagnosis). Random-effects models were used to pool the weighted mean differences comparing levels of adipokines between GDM cases and non-GDM controls. Of 1523 potentially relevant articles, we included 25 prospective studies relating adipokines to incident GDM. Our meta-analysis of nine prospective studies on adiponectin and eight prospective studies on leptin indicated that adiponectin levels in the first or early second trimester of pregnancy were 2.25 μg/ml lower (95% CI: 1.75-2.75), whereas leptin levels were 7.25 ng/ml higher (95% CI 3.27-11.22), among women who later developed GDM than women who did not. Prospective data were sparse and findings were inconsistent for visfatin, retinol binding protein (RBP-4), resistin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vaspin. We did not identify prospective studies for several novel adipokines, including chemerin, apelin, omentin, or adipocyte fatty acid-binding protein. Moreover, no published prospective studies with longitudinal assessment of adipokines and incident GDM were identified. Adiponectin levels in the first or second trimester of pregnancy are lower among pregnant women who later develop GDM than non-GDM women, whereas leptin levels are higher. Well-designed prospective studies with longitudinal assessment of adipokines during pregnancy are needed to understand the trajectories and dynamic associations of adipokines with GDM risk. Published by Elsevier Inc.
    Metabolism: clinical and experimental 01/2015; 64(6). DOI:10.1016/j.metabol.2015.01.013 · 3.89 Impact Factor
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    • "Increased expression of adiponectin in 3 T3-L1 cells also promotes adipocyte differentiation, lipid accumulation, and insulin sensitivity (Fu et al., 2005). Adiponectin has been reported to alleviate insulin resistance by the activation of fatty acid transporter CD36 (Yamauchi et al., 2001). Therefore, all of our results suggest that UMB treatment may stimulate the adipogenesis through C/EBPα-, PPARγ-, and SREBP1c- mediated adipogenesis related to the downstream adipocyte-specific genes aP2, LPL, FAS, CD36, and adiponectin. "
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    ABSTRACT: Umbelliferone (UMB), a natural product of coumarin family, has been shown to reduce blood glucose and to improve lipid profiles in streptozotocin (STZ)-induced diabetic rats. Our objective was to examine the effect of UMB on adipogenesis by investigating its stimulatory effect on lipid accumulation and mRNA expression of adipogenic transcription factors and adipocyte-specific genes in 3 T3-L1 preadipocyte culture. An Oil Red O staining was used to monitor lipid accumulation, and we found that UMB treatment at concentration range of 10–100 μM significantly increased lipid accumulation of differentiating 3 T3-L1 cells. At the molecular level of adipogenesis, we examined the mRNA expression of adipogenic transcription factors, peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and sterol regulatory element-binding protein 1c. Those transcription factors were increased by UMB at 10–100 μM. Interestingly, UMB also stimulated the mRNA expression of adipocyte-specific genes, adipocyte fatty acid-binding protein, lipoprotein lipase, fatty acid synthase, fatty acid translocase, and adiponectin. Our findings indicate that the stimulatory effect of UMB on adipocyte differentiation likely occurs through up-regulation of adipogenic transcription factors and downstream adipocyte-specific gene expression. Copyright © 2014 John Wiley & Sons, Ltd.
    Phytotherapy Research 11/2014; 28(11). DOI:10.1002/ptr.5180 · 2.66 Impact Factor
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