New discovery in weight loss treatment! Academia Sinica finds the key to burning fat

Obesity not only affects appearance, but is also closely related to diseases such as diabetes, cardiovascular disease, stroke and cancer. Therefore, how to improve diet-induced obesity has always been a global health, social and economic issue. The team led by Researcher Ruan Lirong from the Genomics Research Center of Academia Sinica has recently discovered that obesity is related to excessive expression of a gene Naa10p in the human body. In the future, by inhibiting the enzyme activity of Naa10p in adult adipose tissue, diet-induced obesity may be suppressed. The relevant research results have been published in the internationally renowned journal Molecular Cell and selected as a special article in Nature Structure and Molecular Biology.

Obesity not only affects appearance, but is also closely related to diseases such as diabetes, cardiovascular disease, stroke and cancer.

Naa10p is an important protein for human development, but excessive amounts can lead to obesity and even cancer

What is Naa10p? Researcher Ruan Lirong from the Genomics Research Center of the Academia Sinica said that the full name of Naa10p is Na-acetyltransferase 10 protein (Naa10p), which is mainly responsible for the N-terminal acetylation of newly generated proteins in the cytoplasm and participates in regulating physiological functions such as cell cycle, growth and apoptosis. It is an important protein during human development, but excessive Naa10p can lead to obesity and even cancer.

Previous studies have shown that when Naa10p mutates in the human body, it can lead to developmental delays. In severe cases, such as the rare disease Ogden syndrome, patients often die before the age of one and a half. These patients are characterized by having very little subcutaneous fat. Therefore, based on the above results, researcher Ruan Lirong's team hopes to further understand whether Naa10p is related to fat production and metabolism.

Colored fat enhances energy expenditure, and once deficient, it leads to the expansion of white adipose tissue, where fat is stored, which can cause diet-induced obesity.

Not just experiments on mice! The study also found that the expression of the human Naa10p gene is also positively correlated with obesity

It is now known that beige adipocytes, which are the dominant cells in the human body that consume energy and produce heat, play an important role in the process of weight loss. Because beige fat can enhance energy expenditure, once a deficiency occurs, it will lead to the expansion of white adipose tissue that stores fat, which in turn causes diet-induced obesity (DIO). Experiments have shown that mice lacking beige fat develop obesity and systemic metabolic dysfunction. Therefore, one of the most attractive therapies for treating obesity is to promote the proliferation of beige adipocytes in white adipose tissue.

In order to further explore the mechanism of action of Naa10p and fat metabolism, the research team led by Ruan Lirong used mice with systemic and fat-specific deletion of Naa10p to verify whether Naa10p affects the differentiation of beige adipocytes and inhibits energy consumption and heat production. The results showed that mice with the Naa10p gene deleted were not only significantly thinner, but also greatly promoted the production of beige fat cells and thermogenesis, thereby preventing obesity caused by a high-fat diet.

In addition to the mouse experiments, researcher Ruan Lirong also collaborated with Dr. Zhuang Limin and Dr. Chang Yicheng of the Department of Internal Medicine at National Taiwan University Hospital to examine human adipose tissue to understand the correlation between Naa10p and human obesity. The research team found that the gene expression level of human Naa10p is also positively correlated with obesity.

New strategy for obesity treatment: Inhibiting the activity of Naa10p enzyme in adult adipose tissue helps

Researcher Ruan Lirong has been committed to Naa10p-related research for a long time. In 2010, she discovered that overexpression of human Naa10p can cause methylation of the promoter of tumor suppressor genes by interacting with DNA methylase, thereby inhibiting the expression of tumor suppressor genes and leading to lung cell carcinogenesis. A 2017 study found that Naa10p can maintain genome-wide methylation in mouse embryos and stem cells, mark imprinted alleles, and maintain genome imprinting through the whole-body knockout of the Naa10p gene in mice.

In the future, if we can successfully inhibit the enzyme activity of Naa10p in adult adipose tissue, it will help inhibit the occurrence of diet-induced obesity and provide a new strategy for the treatment of obesity.

Now, the research team's new research results on Naa10p not only confirm the mechanism by which Naa10p causes obesity, but also propose the connection between obesity and cancer. In the future, if we can successfully inhibit the enzyme activity of Naa10p in adult adipose tissue, it will help inhibit the occurrence of diet-induced obesity and provide a new strategy for the treatment of obesity.

The main corresponding author of this paper is Researcher Ruan Lirong of Academia Sinica, and the first author and co-corresponding author is Dr. Li Zhencheng, a postdoctoral researcher at Academia Sinica, who performed the main experiments. The participating researchers include members of Ruan Lirong's laboratory: Shi Yijun, a master's student at the Institute of Molecular Medicine, research assistant Kang Minglun, and Ramanan Devaraj, a doctoral candidate in the institute's International Graduate Program, as well as Dr. Zhuang Limin and Dr. Chang Yicheng of the National Taiwan University Hospital.