Bif-1 deficiency impairs lipid homeostasis and causes obesity accompanied by insulin resistance

• Published in: Scientific reports 2016-02, Vol.6 (1), p.20453-20453, Article 20453
• Main Authors: Liu, Ying, Takahashi, Yoshinori, Desai, Neelam, Zhang, Jun, Serfass, Jacob M., Shi, Yu-Guang, Lynch, Christopher J., Wang, Hong-Gang
• Format: Article
• Language: English
• Subjects: 631/443/319/1642/393; 631/443/319/2723; Adaptor Proteins, Signal Transducing - deficiency; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Aging; Animals; Autophagy; Autophagy-Related Proteins - genetics; Autophagy-Related Proteins - metabolism; Fasting; Food intake; Homeostasis; Humanities and Social Sciences; Hypertrophy; Insulin; Insulin resistance; Insulin Resistance - genetics; Lipid Droplets - metabolism; Lipid Droplets - pathology; Lipid metabolism; Lipid Metabolism - genetics; Lipid turnover; Lipids; Lipolysis; Liver; Lysosomal Membrane Proteins - genetics; Lysosomal Membrane Proteins - metabolism; Membrane proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Knockout; multidisciplinary; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Phagocytosis; Science; Tumorigenesis; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20453

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.