Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance
Liver kinase B1 (Lkb1) and mammalian target of rapamycin (mTOR) are key regulators of energy metabolism and cell growth. We have previously reported that adipocyte-specific KO of Lkb1 or mTOR in mice results in distinct developmental and metabolic phenotypes. Here, we aimed to assess how genetic KO...
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Elsevier
2018-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520330960 |
| _version_ | 1818691047426883584 |
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| author | Yan Xiong Ziye Xu Yizhen Wang Shihuan Kuang Tizhong Shan |
| author_facet | Yan Xiong Ziye Xu Yizhen Wang Shihuan Kuang Tizhong Shan |
| author_sort | Yan Xiong |
| collection | DOAJ |
| description | Liver kinase B1 (Lkb1) and mammalian target of rapamycin (mTOR) are key regulators of energy metabolism and cell growth. We have previously reported that adipocyte-specific KO of Lkb1 or mTOR in mice results in distinct developmental and metabolic phenotypes. Here, we aimed to assess how genetic KO of both Lkb1 and mTOR affects adipose tissue development and function in energy homeostasis. We used Adiponectin-Cre to drive adipocyte-specific double KO (DKO) of Lkb1 and mTOR in mice. We performed indirect calorimetry, glucose and insulin tolerance tests, and gene expression assays on the DKO and WT mice. We found that DKO of Lkb1 and mTOR results in reductions of brown adipose tissue and inguinal white adipose tissue mass, but in increases of liver mass. Notably, the DKO mice developed fatty liver and insulin resistance, but displayed improved glucose tolerance after high-fat diet (HFD)-feeding. Interestingly, the DKO mice were protected from HFD-induced obesity due to their higher energy expenditure and lower expression levels of adipogenic genes (CCAAT/enhancer binding protein α and PPARγ) compared with WT mice. These results together indicate that, compared with Lkb1 or mTOR single KOs, Lkb1/mTOR DKO in adipocytes results in overlapping and distinct metabolic phenotypes, and mTOR KO largely overrides the effect of Lkb1 KO. |
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| language | English |
| last_indexed | 2024-12-17T12:35:41Z |
| publishDate | 2018-01-01 |
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| spelling | doaj.art-89732cdd9b2a49658e969a7f5f6f9bf02022-12-21T21:48:18ZengElsevierJournal of Lipid Research0022-22752018-01-01596974981Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistanceYan Xiong0Ziye Xu1Yizhen Wang2Shihuan Kuang3Tizhong Shan4Department of Animal Sciences, Purdue University, West Lafayette, IN 47907; College of Life Science and Technology, Southwest Minzu University, Chengdu, Sichuan 610041, China; Joint Laboratory of Lipid Metabolism, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100193, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaTo whom correspondence should be addressed.; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907; Joint Laboratory of Lipid Metabolism, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100193, ChinaTo whom correspondence should be addressed.; College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907Liver kinase B1 (Lkb1) and mammalian target of rapamycin (mTOR) are key regulators of energy metabolism and cell growth. We have previously reported that adipocyte-specific KO of Lkb1 or mTOR in mice results in distinct developmental and metabolic phenotypes. Here, we aimed to assess how genetic KO of both Lkb1 and mTOR affects adipose tissue development and function in energy homeostasis. We used Adiponectin-Cre to drive adipocyte-specific double KO (DKO) of Lkb1 and mTOR in mice. We performed indirect calorimetry, glucose and insulin tolerance tests, and gene expression assays on the DKO and WT mice. We found that DKO of Lkb1 and mTOR results in reductions of brown adipose tissue and inguinal white adipose tissue mass, but in increases of liver mass. Notably, the DKO mice developed fatty liver and insulin resistance, but displayed improved glucose tolerance after high-fat diet (HFD)-feeding. Interestingly, the DKO mice were protected from HFD-induced obesity due to their higher energy expenditure and lower expression levels of adipogenic genes (CCAAT/enhancer binding protein α and PPARγ) compared with WT mice. These results together indicate that, compared with Lkb1 or mTOR single KOs, Lkb1/mTOR DKO in adipocytes results in overlapping and distinct metabolic phenotypes, and mTOR KO largely overrides the effect of Lkb1 KO.http://www.sciencedirect.com/science/article/pii/S0022227520330960adiposemetabolismliver kinase B1mammalian target of rapamycin |
| spellingShingle | Yan Xiong Ziye Xu Yizhen Wang Shihuan Kuang Tizhong Shan Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance Journal of Lipid Research adipose metabolism liver kinase B1 mammalian target of rapamycin |
| title | Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance |
| title_full | Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance |
| title_fullStr | Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance |
| title_full_unstemmed | Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance |
| title_short | Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced obesity, but results in insulin resistance |
| title_sort | adipocyte specific dko of lkb1 and mtor protects mice against hfd induced obesity but results in insulin resistance |
| topic | adipose metabolism liver kinase B1 mammalian target of rapamycin |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520330960 |
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