Adipose KLF15 Controls Lipid Handling to Adapt to Nutrient Availability
Keiichiro Matoba,
Yuan Lu,
Rongli Zhang,
Eric R. Chen,
Panjamaporn Sangwung,
Benlian Wang,
Domenick A. Prosdocimo,
Mukesh K. Jain
Affiliations
Keiichiro Matoba
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
Yuan Lu
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
Rongli Zhang
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
Eric R. Chen
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
Panjamaporn Sangwung
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
Benlian Wang
Center for Proteomics and Bioinformatics and Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA
Domenick A. Prosdocimo
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
Mukesh K. Jain
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
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.
