Nat.Comm:胰岛素与胰岛素样生长因子作用新进展
2012-06-17 mili 生物谷
人体存在两种脂肪,白色脂肪堆积在皮下,存储多余热量;棕色脂肪负责分解白色脂肪,避免引起肥胖。胰岛素和胰岛素样生长因子1(insulin-like growth factor 1,IGF-1)在脂肪细胞的分化、葡萄糖耐量和胰岛素敏感度的调解中扮演着重要角色。 为了研究机体内胰岛素和IGF-1相关途径是如何协同作用的,研究人员制作了组织特异性基因敲除模型。研究人员在小鼠中同时敲除了胰岛素和IGF-1
人体存在两种脂肪,白色脂肪堆积在皮下,存储多余热量;棕色脂肪负责分解白色脂肪,避免引起肥胖。胰岛素和胰岛素样生长因子1(insulin-like growth factor 1,IGF-1)在脂肪细胞的分化、葡萄糖耐量和胰岛素敏感度的调解中扮演着重要角色。
为了研究机体内胰岛素和IGF-1相关途径是如何协同作用的,研究人员制作了组织特异性基因敲除模型。研究人员在小鼠中同时敲除了胰岛素和IGF-1受体,这样脂肪细胞中的所有与胰岛素或者IGF-1有关的通路都被阻断了。研究人员发现,这种FIGIRKO小鼠中,白色和棕色脂肪量都显着减少,并且FIGIRKO小鼠能够抵抗高脂饮食所引起的肥胖、衰老和葡萄糖耐受不良。与正常小鼠相比,FIGIRKO小鼠的机体能量消耗更大,但是当把这种小鼠置于低温条件下时,它们没有维持自身体温的能力。在FIGIRKO小鼠体内,棕色脂肪细胞的活动显着减少,但是对β3受体十分敏感。
研究人员据此得出结论,胰岛素和IGF-1途径在调节白色脂肪和棕色脂肪生长中有重要作用。缺失这些途径会导致基础代谢率提高和产热障碍。(生物谷 Bioon.com )
doi:10.1038/ncomms1905
PMC:
PMID:
Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling
Jeremie Boucher, Marcelo A. Mori, Kevin Y. Lee, Graham Smyth, Chong Wee Liew, Yazmin Macotela, Michael Rourk, Matthias Bluher, Steven J. Russell & C. Ronald Kahn
Insulin and insulin-like growth factor 1 (IGF-1) have important roles in adipocyte differentiation, glucose tolerance and insulin sensitivity. Here to assess how these pathways can compensate for each other, we created mice with a double tissue-specific knockout of insulin and IGF-1 receptors to eliminate all insulin/IGF-1 signalling in fat. These FIGIRKO mice had markedly decreased white and brown fat mass and were completely resistant to high fat diet-induced obesity and age- and high fat diet-induced glucose intolerance. Energy expenditure was increased in FIGIRKO mice despite a >85% reduction in brown fat mass. However, FIGIRKO mice were unable to maintain body temperature when placed at 4 °C. Brown fat activity was markedly decreased in FIGIRKO mice but was responsive to β3-receptor stimulation. Thus, insulin/IGF-1 signalling has a crucial role in the control of brown and white fat development, and, when disrupted, leads to defective thermogenesis and a paradoxical increase in basal metabolic rate.
作者:mili
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