Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?
Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?
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DOI：
10.1530/joe-12-0505
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发表时间：
2013-03
期刊：
影响因子：
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通讯作者：
Berryman DE
中科院分区：
文献类型：
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作者：
Lubbers ER;List EO;Jara A;Sackman-Sala L;Cordoba-Chacon J;Gahete MD;Kineman RD;Boparai R;Bartke A;Kopchick JJ;Berryman DE
脂联素与长寿呈正相关，与多种肥胖相关疾病呈负相关。虽然脂联素有几种循环形式，但高分子量（HMW）形式已被认为具有主要的生物活性。脂联素基因表达和同源血清蛋白水平在具有改变的生长激素（GH）信号传导的小鼠中是特别感兴趣的，因为这些小鼠表现出与胰岛素敏感性和寿命正相关的极端肥胖，而不是这些因素的典型负相关。虽然一些研究报告了GH信号改变的年轻成年小鼠的总脂联素水平，但仍有许多问题尚未解决，包括脂联素水平随年龄增长的变化，HMW形式的总脂联素比例，脂肪来源，GH与IGF 1的差异效应。因此，本研究的目的是使用具有改变的GH信号传导的各种小鼠系来解决这些问题。我们的研究结果表明，脂联素通常与GH活性呈负相关，无论年龄大小。此外，HMW脂联素的量始终与总脂联素水平相关，而不一定与先前报道的这些小鼠的寿命或胰岛素敏感性相关。有趣的是，循环脂联素水平与腹股沟脂肪量密切相关，这意味着GH对脂联素的影响具有库特异性。有趣的是，rbGH，而不是IGF 1，降低循环总脂联素和HMW脂联素水平。总之，这些结果填补了GH和脂联素相关文献中的重要空白，并质疑了经常报告的总脂联素和HMW脂联素与胰岛素敏感性和寿命的相关性。
Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH versus IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying the effects of GH on adiponectin are depot-specific. Interestingly rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity.