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: Byeong Tak Jeon, Kyung Eun Kim, Rok Won Heo, Hyun Joo Shin, Chin-ok Yi, Young-Sool Hah, Won-Ho Kim, Sang-Il Lee, Gu Seob Roh
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 29 Issue 3 Pg. 635-43 (Sep 2014) ISSN: 1573-7365 [Electronic] United States
• PMID: 24756314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Leptin
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Animals
• Diet, High-Fat
• Fatty Liver (genetics, metabolism, pathology)
• Glucose Tolerance Test
• Hypothalamus (metabolism, pathology)
• Inflammation (genetics, metabolism, pathology)
• Insulin (blood)
• Insulin Resistance (genetics)
• Leptin (blood)
• Male
• Mice
• Mice, Knockout
• Myeloid Cells (metabolism, pathology)
• Sirtuin 1 (genetics, metabolism)