2017
Cell Rep. 2017 Dec 12;21(11):3129-3140. doi: 10.1016/j.celrep.2017.11.032.
Adipose KLF15 Controls Lipid Handling to Adapt to Nutrient Availability
Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA. Department of Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan. Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Center for Proteomics and Bioinformatics and Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA.
Service type: Knockout mice
Abstract
Adipose tissue stores energy in the form of triglycerides. The ability to regulate triglyceride synthesis and breakdown based on nutrient status (e.g., fed versus fasted) is critical for physiological homeostasis and dysregulation of this process can contribute to metabolic disease. Whereas much is known about hormonal control of this cycle, transcriptional regulation is not well understood. Here, we show that the transcription factor Kruppel-like factor 15 (KLF15) is critical for the control of adipocyte lipid turnover. Mice lacking Klf15 in adipose tissue (AK15KO) display decreased adiposity and are protected from diet-induced obesity. Mechanistic studies suggest that adipose KLF15 regulates key genes of triglyceride synthesis and inhibits lipolytic action, thereby promoting lipid storage in an insulin-dependent manner. Finally, AK15KO mice demonstrate accelerated lipolysis and altered systemic energetics (e.g., locomotion, ketogenesis) during fasting conditions. Our study identifies adipose KLF15 as an essential regulator of adipocyte lipid metabolism and systemic energy balance.
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