Effects of myeloid sirtuin 1 deficiency on hypothalamic neurogranin in mice fed a high-fat diet |
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Authors: | Kyung Eun Kim Eun Ae Jeong Hyun Joo Shin Jong Youl Lee Eun Bee Choi Hyeong Seok An Kyung-Ah Park Zhen Jin Dong Kun Lee Tamas L. Horvath Gu Seob Roh |
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Affiliation: | 1. Department of Anatomy and Convergence Medical Science, Bio Anti-aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam, 52777, Republic of Korea;2. Department of Physiology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam, 52777, Republic of Korea;3. Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA |
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Abstract: | Hypothalamic inflammation has been known as a contributor to high-fat diet (HFD)-induced insulin resistance and obesity. Myeloid-specific sirtuin 1 (SIRT1) deletion aggravates insulin resistance and hypothalamic inflammation in HFD-fed mice. Neurogranin, a calmodulin-binding protein, is expressed in the hypothalamus. However, the effects of myeloid SIRT1 deletion on hypothalamic neurogranin has not been fully clarified. To investigate the effect of myeloid SIRT1 deletion on food intake and hypothalamic neurogranin expression, mice were fed a HFD for 20 weeks. Myeloid SIRT1 knockout (KO) mice exhibited higher food intake, weight gain, and lower expression of anorexigenic proopiomelanocortin in the arcuate nucleus than WT mice. In particular, KO mice had lower ventromedial hypothalamus (VMH)-specific neurogranin expression. However, SIRT1 deletion reduced HFD-induced hypothalamic neurogranin. Furthermore, hypothalamic phosphorylated AMPK and parvalbumin protein levels were also lower in HFD-fed KO mice than in HFD-fed WT mice. Thus, these findings suggest that myeloid SIRT1 deletion affects food intake through VMH-specific neurogranin-mediated AMPK signaling and hypothalamic inflammation in mice fed a HFD. |
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Keywords: | Obesity Sirtuin 1 Food intake Neurogranin Hypothalamus |
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