Leukemia inhibitory factor suppresses hepatic de novo lipogenesis and induces cachexia in mice.
Leukemia inhibitory factor suppresses hepatic de novo lipogenesis and induces cachexia in mice.
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DOI：
10.1038/s41467-024-44924-w
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发表时间：
2024-01-20
影响因子：
16.6
通讯作者：
Hu, Wenwei
中科院分区：
文献类型：
--
作者：
Yang, Xue;Wang, Jianming;Chang, Chun-Yuan;Zhou, Fan;Liu, Juan;Xu, Huiting;Ibrahim, Maria;Gomez, Maria;Guo, Grace L.;Liu, Hao;Zong, Wei-Xing;Wondisford, Fredric E.;Su, Xiaoyang;White, Eileen;Feng, Zhaohui;Hu, Wenwei
癌症恶病质是一种全身代谢综合征，其特征是非自愿体重减轻以及肌肉和脂肪组织消耗。恶病质的潜在机制仍然知之甚少。白血病抑制因子（LIF）是一种多功能细胞因子，已被认为是恶病质诱导因子。在具有条件性 LIF 表达的转基因小鼠模型中，LIF 的全身升高会诱导恶病质。 LIF 过度表达会减少肝脏中的脂肪从头生成并破坏脂质稳态。肝脏特异性 LIF 受体敲除可减轻 LIF 诱导的恶病质，这表明 LIF 诱导的肝脏功能变化有助于恶病质。从机制上讲，LIF 过表达激活 STAT3 下调脂质代谢的主要调节因子 PPARα，导致一组参与脂肪生成的 PPARα 靶基因下调，从而减少肝脏中的脂肪生成。通过非诺贝特（一种 PPARα 激动剂）激活 PPARα，可恢复肝脏脂质稳态并抑制 LIF 引起的恶病质。这些结果为恶病质提供了有价值的见解，这可能有助于制定治疗癌症恶病质的策略。癌症恶病质是一种全身综合征，其特征是体重急剧减轻以及脂肪组织和骨骼肌质量下降。在这里，作者表明，白血病抑制因子（LIF）（一种分泌的细胞因子）的过度表达会抑制小鼠的脂肪从头生成并诱导恶病质。
Cancer cachexia is a systemic metabolic syndrome characterized by involuntary weight loss, and muscle and adipose tissue wasting. Mechanisms underlying cachexia remain poorly understood. Leukemia inhibitory factor (LIF), a multi-functional cytokine, has been suggested as a cachexia-inducing factor. In a transgenic mouse model with conditional LIF expression, systemic elevation of LIF induces cachexia. LIF overexpression decreases de novo lipogenesis and disrupts lipid homeostasis in the liver. Liver-specific LIF receptor knockout attenuates LIF-induced cachexia, suggesting that LIF-induced functional changes in the liver contribute to cachexia. Mechanistically, LIF overexpression activates STAT3 to downregulate PPARα, a master regulator of lipid metabolism, leading to the downregulation of a group of PPARα target genes involved in lipogenesis and decreased lipogenesis in the liver. Activating PPARα by fenofibrate, a PPARα agonist, restores lipid homeostasis in the liver and inhibits LIF-induced cachexia. These results provide valuable insights into cachexia, which may help develop strategies to treat cancer cachexia. Cancer cachexia is a systemic syndrome characterized by dramatic weight loss and decline in adipose tissue and skeletal muscle mass. Here, the authors show that overexpression of leukemia inhibitory factor (LIF), a secreted cytokine, suppresses de novo lipogenesis and induces cachexia in mice.
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DOI：
10.1002/hep.27744
发表时间：
2015-08
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Ghonem NS;Assis DN;Boyer JL
通讯作者：
Boyer JL
DOI：
10.1002/jcsm.12346
发表时间：
2018-12
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Kandarian SC;Nosacka RL;Delitto AE;Judge AR;Judge SM;Ganey JD;Moreira JD;Jackman RW
通讯作者：
Jackman RW
影响因子：
56.9
作者：
Das, Suman K.;Eder, Sandra;Hoefler, Gerald
通讯作者：
Hoefler, Gerald
影响因子：
15.9
作者：
Liu, Juan;Zhang, Cen;Feng, Zhaohui
通讯作者：
Feng, Zhaohui
评估压力对实验室小鼠喂养行为的影响。
影响因子：
7.7
作者：
Francois M;Canal Delgado I;Shargorodsky N;Leu CS;Zeltser L
通讯作者：
Zeltser L