Myeloid-specific deletion of SIRT1 increases hepatic steatosis and hypothalamic inflammation in mice fed a high-fat diet

• Published in: Metabolic brain disease Vol. 29; no. 3; pp. 635 - 643
• Main Authors: Jeon, Byeong Tak, Kim, Kyung Eun, Heo, Rok Won, Shin, Hyun Joo, Yi, Chin-ok, Hah, Young-Sool, Kim, Won-Ho, Lee, Sang-Il, Roh, Gu Seob
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-09-2014; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Diet, High-Fat; Fatty Liver - genetics; Fatty Liver - metabolism; Fatty Liver - pathology; Glucose Tolerance Test; Hypothalamus - metabolism; Hypothalamus - pathology; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Insulin - blood; Insulin Resistance - genetics; Leptin - blood; Male; Metabolic Diseases; Mice; Mice, Knockout; Myeloid Cells - metabolism; Myeloid Cells - pathology; Neurology; Neurosciences; Oncology; Research Article; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Obesity; Inflammation; Hepatic steatosis; Hypothalamus; SIRT1
• DOI: 10.1007/s11011-014-9542-3
• EISSN: 1573-7365
• ISSN: 0885-7490

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.