title: Bif-1 deficiency impairs lipid homeostasis and causes obesity accompanied by insulin resistance.
abstract: Bif-1 is a membrane-curvature inducing protein that is implicated in the regulation of autophagy and tumorigenesis. Here, we report that Bif-1 plays a critical role in regulating lipid catabolism to control the size of lipid droplets and prevent the development of obesity and insulin resistance upon aging or dietary challenge. Our data show that Bif-1 deficiency promotes the expansion of adipose tissue mass without altering food intake or physical activities. While Bif-1 is dispensable for adipose tissue development, its deficiency reduces the basal rate of adipose tissue lipolysis and results in adipocyte hypertrophy upon aging. The importance of Bif-1 in lipid turnover is not limited to adipose tissue since fasting and refeeding-induced lipid droplet clearance is also attenuated by Bif-1 loss in the liver. Interestingly, obesity induced by a high fat-diet or Bif-1 deficiency downregulates the expression of proteins involved in the autophagy-lysosomal pathway, including Atg9a and Lamp1 in the adipose tissue. These findings thus identify Bif-1 as a novel regulator of lipid homeostasis to prevent the pathogenesis of obesity and its associated metabolic complications.
authors: Department of Pharmacology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors: Ying
authors: Y
authors: Liu
authors: Department of Pediatrics, Penn State University College of Medicine, Hershey, PA 17033, USA.|Penn State Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors: Yoshinori
authors: Y
authors: Takahashi
authors: Department of Pediatrics, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors: Neelam
authors: N
authors: Desai
authors: epartment of Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors: Jun
authors: J
authors: Zhang
authors: Department of Pharmacology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors: Jacob M
authors: JM
authors: Serfass
authors: epartment of Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors: Yu-Guang
authors: YG
authors: Shi
authors: epartment of Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors: Christopher J
authors: CJ
authors: Lynch
authors: Department of Pharmacology, Penn State University College of Medicine, Hershey, PA 17033, USA.|Department of Pediatrics, Penn State University College of Medicine, Hershey, PA 17033, USA.|Penn State Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors: Hong-Gang
authors: HG
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency*; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000071183:Autophagy-Related Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D066292:Lipid Droplets / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; C549015:Atg9A protein, mouse; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C486100:Sh3glb1 protein, mouse