title: Fabp4-Cre-mediatedSirt6deletion impairs adipose tissue function and metabolic homeostasis in mice.
abstract: SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient inSirt6using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouseFabp4orAdipoqgene promoter were chosen for this study. TheSirt6-knockout mice generated by the Fabp4-Cre line (Sirt6f/f:Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, theSirt6f/f:Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, theSirt6knockout mice generated by the Adipoq-Cre line (Sirt6f/f:Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis.
authors.affiliation: Department of Forensic MedicineXinxiang Medical University, Xinxiang, Henan, China xwxiong@xxmu.edu.cn xcdong@iu.edu.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Xiong
authors.affiliation: School of Basic Medical SciencesXinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular BiologyIndiana University School of Medicine, Indianapolis, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Basic Medical SciencesXinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Fan
authors.affiliation: School of Basic Medical SciencesXinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Xinlai
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Biochemistry and Molecular BiologyIndiana University School of Medicine, Indianapolis, USA xwxiong@xxmu.edu.cn xcdong@iu.edu.
authors.forename: X Charlie
authors.initials: XC
authors.lastname: Dong
mesh_terms: D017667:Adipocytes; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D029968:Escherichia coli Proteins; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D029968:Escherichia coli Proteins; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D011993:Recombinant Fusion Proteins; C479802:glucose indicator protein, E coli; C501860:Sirt6 protein, mouse; D037761:Sirtuins
keywords: Adipoq-Cre; Fabp4-Cre; Sirt6; adipocyte; conditional gene knockout