In our daily life, there is an oddity: some people with a huge stomach can keep slender while someone of big size may put on weight very easily even on water. Have you ever thought it is the obesity factor that is taking effects. Does it sound exciting if obesity factor is figured out and applied by scientists to effectively fight against obesity and treat diseases?

Recently, the team of Prof. Song Baoliang from College of Life Sciences of Wuhan University has discovered that GPNMB secreted from liver is a new sort of adipokine. It synthesizes genes and inhibited body heat production by regulating lipid in adipose tissue, and eventually exacerbates diet-induced obesity and insulin resistance. Moreover, Prof. Song’s team found that GPNMB in antibody and blood has a good therapeutic effect on obesity and diabetes, which is of great importance to understand and treat metabolic diseases.

On May 6th, Nature Metabolism, the sub-journal of Nature published the research online, and the same journal also gave it a preview.

The paper is entitled "Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance". Dr. Gong Xuemin, Li Yunfeng, Associate Professor Luo Wei, postdoctoral Wei Jian, and Dr. Wang Jiqiu from Shanghai Jiao Tong University, School of Medicine are co-first authors. Professor Song Baoliang and Associate Professor Qi Wei from ShanghaiTech University are both corresponding authors. The research is funded by the National Natural Science Foundation of China and the Ministry of Science and Technology.

According to the World Health Organization, more than 1.9 billion adults aged 18 and over were reported overweight in 2016, of which more than 650 million were obese. Obesity can attribute to many factors such as genetics and environment. It not only leads to unsatisfactory appearance, but also brings disease risks for such as diabetes, fatty liver and cardiovascular disease. As an organic whole, the living body's lipid metabolism process is strictly regulated in the cell. In addition, there are various forms of interaction among every tissue and organ.

Professor Song’s previous studies discovered that specific knockdown of ubiquitin ligase gp78 (L-gp78-/-) in the liver can lead to inhibition of the SREBP pathway. Interestingly, while the ability to synthesize lipids in the liver decreased, the lipid synthesis capacity of adipose tissue was compensated up, suggesting that the liver secretes some "obesity factor" that promotes lipid synthesis in adipose tissue.

This phenomenon leads the researchers to the discovery that the GPNMB protein secreted by the liver can significantly increase the degree of obesity and the lipid synthesis ability of adipose tissue, inhibit the body's heat production, reduce energy consumption, and aggravate insulin resistance. The GPNMB neutralizing antibody effectively reverses the phenotype of obese mice, reduces the weight of adipose tissue, reduces the expression of adipose tissue lipid synthesis genes, promotes the production of adipose tissue, and weakens insulin resistance. The research findings indicate that GPNMB is a novel "obesity factor" and demonstrate that targeting GPNMB is effective in treating obesity and diabetes.

Rewritten by Zhao Mengchen

Edited by Cao Siyi, Shen Yuxi and Hu Sijia