title: Myeloid-specific deletion of SIRT1 increases hepatic steatosis and hypothalamic inflammation in mice fed a high-fat diet.
abstract: Obesity-induced fatty liver disease is associated with increased hypothalamic inflammation. Previous reports have demonstrated that the deletion of SIRT1 in hepatocytes increases hepatic steatosis and inflammation. Using myeloid cell-specific SIRT1 knockout (KO) mice, we investigated whether ablation of SIRT1 in macrophages plays a role in regulating hepatic steatosis and hypothalamic inflammation. When challenged with a high-fat diet (HFD) for 24 weeks, hyperleptinemia, hyperinsulinemia, hepatic steatosis and macrophage infiltrations in HFD-fed KO mice were increased compared with HFD-fed WT mice. Hypothalamic expression levels of iba1 were increased in HFD-fed KO mice compared with HFD-fed WT mice. In particular, the expression levels of choline acetyltransferase were decreased in the hypothalamus of HFD-fed KO mice compared with HFD-fed WT mice. Thus, our findings suggest that SIRT1 plays a key role for hepatic steatosis and hypothalamic inflammation and that anti-inflammatory effect of SIRT1 may be important for the prevention of obesity-induced metabolic syndromes.
authors.affiliation: Department of Neurological Surgery, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Byeong Tak
authors.initials: BT
authors.lastname: Jeon
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Kim
authors.forename: Rok Won
authors.initials: RW
authors.lastname: Heo
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Shin
authors.forename: Chin-ok
authors.initials: CO
authors.lastname: Yi
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.forename: Won-Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Sang-Il
authors.initials: SI
authors.lastname: Lee
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D020738:Leptin; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
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