Deletion of the androgen receptor in adipose tissue in male mice elevates retinol binding protein 4 and reveals independent effects on visceral fat mass and on glucose homeostasis.
Deletion of the androgen receptor in adipose tissue in male mice elevates retinol binding protein 4 and reveals independent effects on visceral fat mass and on glucose homeostasis.
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作者：
McInnes KJ;Smith LB;Hunger NI;Saunders PT;Andrew R;Walker BR
睾酮缺乏在患有2型糖尿病的肥胖老年男性中很普遍，但因果关系的方向尚不清楚。睾酮缺乏的雄性和全球雄激素受体(AR)基因敲除的小鼠是胰岛素抵抗的，脂肪增加，但尚不清楚脂肪组织中的AR信号是否介导了体内脂肪的重新分配和改变了血糖稳态。为了研究这一点，产生了脂肪细胞AR选择性敲除的小鼠(Farko)。正常饮食的雄性Farko小鼠肾上腺周围脂肪减少，但胰岛素水平较高，到12个月时，没有肥胖的情况下胰岛素缺乏。在高脂饮食中，Farko小鼠的胰岛素代偿性分泌受损，并出现高血糖，对内脏肥胖的易感性增加。在Farko小鼠中进行的脂肪因子筛查显示，肥胖前血浆和脂肪内视黄醇结合蛋白4(RBP4)有选择性地增加。小鼠3T3脂肪细胞AR的激活下调了RBP4mRNA的表达。我们的结论是，脂肪细胞中的AR信号不仅可以预防高脂饮食诱导的内脏肥胖，还可以调节胰岛素的作用和葡萄糖的稳态，而不依赖于肥胖。小鼠脂肪细胞中的雄激素缺乏类似于人类2型糖尿病，具有早期的胰岛素抵抗和进化中的胰岛素缺乏。
Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age 12 months, were insulin deficient in the absence of obesity. On high-fat diet, fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with increased susceptibility to visceral obesity. Adipokine screening in fARKO mice revealed a selective increase in plasma and intra-adipose retinol binding protein 4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only protects against high-fat diet–induced visceral obesity but also regulates insulin action and glucose homeostasis, independently of adiposity. Androgen deficiency in adipocytes in mice resembles human type 2 diabetes, with early insulin resistance and evolving insulin deficiency.
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影响因子：
29
作者：
Kloeting, Nora;Graham, Timothy E.;Kahn, Barbara B.
通讯作者：
Kahn, Barbara B.
影响因子：
158.5
作者：
Graham, Timothy E.;Yang, Qin;Kahn, Barbara B.
通讯作者：
Kahn, Barbara B.
影响因子：
3.2
作者：
Lanfranco, F;Zitzmann, M;Nieschlag, E
通讯作者：
Nieschlag, E
DOI：
10.1073/pnas.0308114100
发表时间：
2004-02-03
影响因子：
11.1
作者：
De Gendt, K;Swinnen, JV;Verhoeven, G
通讯作者：
Verhoeven, G
影响因子：
29
作者：
Eguchi J;Wang X;Yu S;Kershaw EE;Chiu PC;Dushay J;Estall JL;Klein U;Maratos-Flier E;Rosen ED
通讯作者：
Rosen ED