Mice deficient in cryptochrome 1 (cry1 (-/-)) exhibit resistance to obesity induced by a high-fat diet.
Mice deficient in cryptochrome 1 (cry1 (-/-)) exhibit resistance to obesity induced by a high-fat diet.
复制标题
DOI：
10.3389/fendo.2014.00049
复制
发表时间：
2014
影响因子：
5.2
通讯作者：
Pichat P
中科院分区：
文献类型：
--
作者：
Griebel G;Ravinet-Trillou C;Beeské S;Avenet P;Pichat P
生物钟紊乱会增加代谢综合征、肥胖和2型糖尿病的风险。生物钟依赖于一个高度调控的转录和翻译循环网络，驱动生物钟控制的基因表达。在这些转录的时钟基因中有隐花色素（Cry1）家族成员，包括Cry1和Cry2。虽然已经很好地描述了时钟基因机制的几个核心成分缺失的代谢影响，但Cry1或Cry2基因的选择性失活尚未被描述。在这项研究中，我们证明了消融Cry1，而不是Cry2，可以防止小鼠高脂肪饮食（HFD）诱导的肥胖。尽管热量摄入相似，但在16周实验结束时，与野生型（WT）幼崽相比，食用HFD的Cry1 - / -小鼠体重增加明显减少（- 18%），脂肪积累减少（- 61%），表明能量消耗增加。血清脂质和葡萄糖谱分析显示Cry1−/−和WT小鼠之间没有差异。Cry1−/−和Cry2−/−小鼠在体重、脂肪和蛋白质含量以及食物消耗方面与WT对照组没有区别，当它们被允许无限制地获得标准啮齿动物饮食时。我们得出结论，尽管在稳态营养条件下，Cry1信号可能不是维持能量稳态所必需的，但在变化的营养条件下，Cry1可能在重新调节能量平衡中发挥作用。这些研究强调了生物钟基因在能量稳态中的重要作用，并表明Cry1可能是抗肥胖治疗的靶点。
Disruption of circadian clock enhances the risk of metabolic syndrome, obesity, and type 2 diabetes. Circadian clocks rely on a highly regulated network of transcriptional and translational loops that drive clock-controlled gene expression. Among these transcribed clock genes are cryptochrome (CRY) family members, which comprise Cry1 and Cry2. While the metabolic effects of deletion of several core components of the clock gene machinery have been well characterized, those of selective inactivation of Cry1 or Cry2 genes have not been described. In this study, we demonstrate that ablation of Cry1, but not Cry2, prevents high-fat diet (HFD)-induced obesity in mice. Despite similar caloric intake, Cry1−/− mice on HFD gained markedly less weight (−18%) at the end of the 16-week experiment and displayed reduced fat accumulation compared to wild-type (WT) littermates (−61%), suggesting increased energy expenditure. Analysis of serum lipid and glucose profiles showed no difference between Cry1−/− and WT mice. Both Cry1−/− and Cry2−/− mice are indistinguishable from WT controls in body weight, fat and protein contents, and food consumption when they are allowed unlimited access to a standard rodent diet. We conclude that although CRY signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, Cry1 may play a role in readjusting energy balance under changing nutritional circumstances. These studies reinforce the important role of circadian clock genes in energy homeostasis and suggest that Cry1 is a plausible target for anti-obesity therapy.
登录
查看更多内容
DOI：
10.1073/pnas.0808180106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Scheer, Frank A. J. L.;Hilton, Michael F.;Shea, Steven A.
通讯作者：
Shea, Steven A.
DOI：
10.1097/mco.0b013e32834ad94b
发表时间：
2011-11-01
影响因子：
3.1
作者：
Gimble, Jeffrey M.;Sutton, Gregory M.;Bunnell, Bruce A.
通讯作者：
Bunnell, Bruce A.
昼夜节律的代谢和能量学的融合。
DOI：
10.1126/science.1195027
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bass J;Takahashi JS
通讯作者：
Takahashi JS
影响因子：
2.8
作者：
Dallmann R;Weaver DR
通讯作者：
Weaver DR
影响因子：
29
作者：
Grimaldi B;Bellet MM;Katada S;Astarita G;Hirayama J;Amin RH;Granneman JG;Piomelli D;Leff T;Sassone-Corsi P
通讯作者：
Sassone-Corsi P