FAK signalling controls insulin sensitivity through regulation of adipocyte survival

• Published in: Nature communications 2017-02, Vol.8 (1), p.14360-14360, Article 14360
• Main Authors: Luk, Cynthia T., Shi, Sally Yu, Cai, Erica P., Sivasubramaniyam, Tharini, Krishnamurthy, Mansa, Brunt, Jara J., Schroer, Stephanie A., Winer, Daniel A., Woo, Minna
• Format: Article
• Language: English
• Subjects: 13/106; 13/2; 38; 3T3-L1 Cells; 631/443/319; 631/80/82/23; 64/60; 692/163/2743; 82; Adipocytes; Adipocytes - physiology; Adipose Tissue - cytology; Adipose Tissue - metabolism; Adipose Tissue - physiopathology; Adiposity - drug effects; Adiposity - genetics; Adult; Animals; Apoptosis; Apoptosis - drug effects; Body fat; Cell death; Cell Survival; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diet, High-Fat - adverse effects; Disease Models, Animal; Female; Focal Adhesion Kinase 1 - genetics; Focal Adhesion Kinase 1 - metabolism; Health care networks; Humanities and Social Sciences; Humans; Hypoglycemic Agents - pharmacology; Insulin - metabolism; Insulin resistance; Insulin Resistance - physiology; Kinases; Male; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Middle Aged; multidisciplinary; Obesity; Obesity - etiology; Obesity - metabolism; Obesity - physiopathology; PPAR gamma - agonists; Primary Cell Culture; Proteins; Science; Science (multidisciplinary); Signal Transduction - physiology; Thiazolidinediones - pharmacology; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14360

Focal adhesion kinase (FAK) plays a central role in integrin signalling, which regulates growth and survival of tumours. Here we show that FAK protein levels are increased in adipose tissue of insulin-resistant obese mice and humans. Disruption of adipocyte FAK in mice or in 3T3 L1 cells decreases adipocyte survival. Adipocyte-specific FAK knockout mice display impaired adipose tissue expansion and insulin resistance on prolonged metabolic stress from a high-fat diet or when crossed on an obese db/db or ob/ob genetic background. Treatment of these mice with a PPARγ agonist does not restore adiposity or improve insulin sensitivity. In contrast, inhibition of apoptosis, either genetically or pharmacologically, attenuates adipocyte death, restores normal adiposity and improves insulin sensitivity. Together, these results demonstrate that FAK is required for adipocyte survival and maintenance of insulin sensitivity, particularly in the context of adipose tissue expansion as a result of caloric excess. The kinase FAK is important for integrin signalling and promotes cell survival. Here, the authors demonstrate FAK regulates adipocyte survival, and is particularly important for maintaining insulin sensitivity during adipose tissue expansion in the context of a calorie-rich diet.