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Open AccessArticle

Agrp-Specific Ablation of Scly Protects against Diet-Induced Obesity and Leptin Resistance

Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai‘i, Honolulu, HI 96813, USA
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Nutrients 2019, 11(7), 1693; https://doi.org/10.3390/nu11071693
Received: 28 June 2019 / Revised: 18 July 2019 / Accepted: 20 July 2019 / Published: 23 July 2019
(This article belongs to the Special Issue The Role of Selenium in Health and Disease)
Selenium, an essential trace element known mainly for its antioxidant properties, is critical for proper brain function and regulation of energy metabolism. Whole-body knockout of the selenium recycling enzyme, selenocysteine lyase (Scly), increases susceptibility to metabolic syndrome and diet-induced obesity in mice. Scly knockout mice also have decreased selenoprotein expression levels in the hypothalamus, a key regulator of energy homeostasis. This study investigated the role of selenium in whole-body metabolism regulation using a mouse model with hypothalamic knockout of Scly. Agouti-related peptide (Agrp) promoter-driven Scly knockout resulted in reduced weight gain and adiposity while on a high-fat diet (HFD). Scly-Agrp knockout mice had reduced Agrp expression in the hypothalamus, as measured by Western blot and immunohistochemistry (IHC). IHC also revealed that while control mice developed HFD-induced leptin resistance in the arcuate nucleus, Scly-Agrp knockout mice maintained leptin sensitivity. Brown adipose tissue from Scly-Agrp knockout mice had reduced lipid deposition and increased expression of the thermogenic marker uncoupled protein-1. This study sheds light on the important role of selenium utilization in energy homeostasis, provides new information on the interplay between the central nervous system and whole-body metabolism, and may help identify key targets of interest for therapeutic treatment of metabolic disorders. View Full-Text
Keywords: agrp; hypothalamus; leptin; scly; selenium; selenoprotein; thermogenesis; type 2 diabetes agrp; hypothalamus; leptin; scly; selenium; selenoprotein; thermogenesis; type 2 diabetes
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MDPI and ACS Style

Torres, D.J.; Pitts, M.W.; Hashimoto, A.C.; Berry, M.J. Agrp-Specific Ablation of Scly Protects against Diet-Induced Obesity and Leptin Resistance. Nutrients 2019, 11, 1693.

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