Mice lacking triglyceride synthesis enzymes in adipose tissue are resistant to diet-induced obesity.
Mice lacking triglyceride synthesis enzymes in adipose tissue are resistant to diet-induced obesity.
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DOI：
10.7554/elife.88049
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发表时间：
2023-10-02
期刊：
影响因子：
7.7
通讯作者：
Farese RV Jr
中科院分区：
文献类型：
--
作者：
Chitraju C;Fischer AW;Ambaw YA;Wang K;Yuan B;Hui S;Walther TC;Farese RV Jr
脂肪细胞中的甘油三酯（TG）提供了体内代谢能量的主要储存。TG储存的最佳量是期望的，因为储存TG的能力不足（如在脂肪营养不良中）或超过储存能力（如在肥胖症中）导致代谢疾病。我们假设，小鼠缺乏脂肪细胞中的TG储存将导致脂肪细胞以外的细胞类型中的过量TG储存和伴有代谢疾病的严重脂毒性。为了验证这一假设，我们选择性地删除脂肪细胞（ADGAT DKO小鼠）中的TG合成酶DGAT 1和DGAT 2。正如能量储存耗尽所预期的那样，ADGAT DKO小鼠不能很好地耐受禁食，并且随着长时间禁食，进入麻木状态。然而，ADGAT DKO小鼠出乎意料地在其他方面代谢健康，并且即使在喂食高脂肪饮食时也没有异位蓄积TG或发生相关的代谢紊乱。有利的代谢表型是由能量消耗的激活引起的，部分是通过BAT（棕色脂肪组织）激活和白色脂肪组织的米色化。因此，ADGAT DKO小鼠为研究代谢能量储存与能量消耗的耦合提供了一个迷人的新模型。
Triglycerides (TGs) in adipocytes provide the major stores of metabolic energy in the body. Optimal amounts of TG stores are desirable as insufficient capacity to store TG, as in lipodystrophy, or exceeding the capacity for storage, as in obesity, results in metabolic disease. We hypothesized that mice lacking TG storage in adipocytes would result in excess TG storage in cell types other than adipocytes and severe lipotoxicity accompanied by metabolic disease. To test this hypothesis, we selectively deleted both TG synthesis enzymes, DGAT1 and DGAT2, in adipocytes (ADGAT DKO mice). As expected with depleted energy stores, ADGAT DKO mice did not tolerate fasting well and, with prolonged fasting, entered torpor. However, ADGAT DKO mice were unexpectedly otherwise metabolically healthy and did not accumulate TGs ectopically or develop associated metabolic perturbations, even when fed a high-fat diet. The favorable metabolic phenotype resulted from activation of energy expenditure, in part via BAT (brown adipose tissue) activation and beiging of white adipose tissue. Thus, the ADGAT DKO mice provide a fascinating new model to study the coupling of metabolic energy storage to energy expenditure.