On August 11, 2021, Professor Guozhi Xiao’s team from the School of Medicine at the Southern University of Science and Technology (SUSTech) published a research paper entitled “PINCH loss ameliorates obesity, glucose intolerance, and fatty liver by modulating adipocyte apoptosis in mice” in the top international journal Diabetes. In their study, they demonstrate a previously unknown function of PINCH in control of adipose mass, glucose, and fat metabolism via modulation of adipocyte apoptosis.

Due to changes in eating habits and lifestyles, the incidence of obesity in the population is increasing year by year. The prevalence of obesity-related diseases such as type II diabetes, non-alcoholic fatty liver, and cardiovascular diseases have also increased significantly. On the one hand, it seriously affects the life of patients and even threatens their lives; on the other hand, it also causes tremendous stress on the social medical service system.

Obesity mainly results from abnormal proliferation and hypertrophy of adipocytes. The normal metabolism of adipocytes plays an important role in maintaining body homeostasis. Still, fat dysfunction can cause ectopic lipid accumulation in peripheral tissues, which leads to metabolic disorders such as insulin resistance, fatty liver, and inflammation.

Professor Guozhi Xiao’s team collected samples from obese patients and constructed mouse models. Using cell and molecular biology methods, the team first revealed the important role of PINCH protein in the metabolism of adipose tissue. The researchers observed that the expression of PINCH protein is higher in the adipose tissue of obese mice and obese patients. In normal diet conditions, after adipocyte knockout of PINCH, no obvious metabolic alterations were observed in healthy mice. Meanwhile, down-regulating the expression of PINCH can effectively alleviate the abnormal accumulation of adipocytes and insulin resistance in obese mice. The team also found that knockout of the PINCH gene promotes fat cell apoptosis in obese mice, and knockout of apoptosis-related protein molecule Caspase8 in fat cells can effectively reverse the weight loss and alleviate insulin resistance caused by knockout of PINCH gene.

Therefore, PINCH protein may become a novel target for preventing and treating metabolic diseases, such as obesity and diabetics.

Dr. Huanqing Gao, Assistant Professor of Research of the School of Medicine at SUSTech is the first author of this study. Graduate students Yiming Zhong and Zhen Ding and doctoral student Sixiong Lin, all residing from the School of Medicine at SUSTech, are the co-first authors. Professor Guozhi Xiao and Associate Professor Cao Huiling of the School of Medicine at SUSTech are the co-corresponding authors of this paper.

The work was also supported by the National Science and Technology Major Project and the National Natural Science Foundation of China (NSFC)

Paper link: https://diabetes.diabetesjournals.org/content/early/2021/08/11/db21-0392