New method of improving obesity is coming!

Recently, the international academic journal Diabetes published a study titled "Deletion of ATF4 in AgRP neurons promotes fat loss mainly via increasing energy expenditure" online by Guo Feifan research group from Institute of Nutrition, Shanghai Institute of Life Sciences, Chinese Academy of Sciences. This study found through research using recombinant dog proteins that activation of transcription factor 4 (ATF4) regulates energy balance and lipid metabolism in hypothalamic-specific neurons of AgRP neurons, providing a potential drug target for the treatment of obesity and related metabolic diseases.

In recent years, both in developing and developed countries or in adults and children, obesity are widely prevalent, and it is closely related to a series of metabolic syndrome such as diabetes, fatty liver, dyslipidemia and cardiovascular diseases, becoming a great threat to human health. Therefore, the study of obesity development mechanism is particularly important. Changes in body weight are caused by imbalances in energy intake and energy expenditure and the central nervous system, especially the hypothalamus, play a key role in regulating energy balance.

Our brain contains a variety of specific types of neurons which have different functions, regulating the body's behavior and metabolic balance. The arcuate nucleus (ARC) of the hypothalamus contains two types of neurons that regulate metabolism: one is appetite-suppressing neurons, such as pro-opioid (POMC) neurons; the other is appetite-promoting neurons, including Neuropeptide Y (NPY) and gerbil peptide gene-related protein (AgRP) neurons. AgRP neurons can release the AgRP protein and inhibit the activity of POMC neurons, thus promoting increased food intake; it also affects energy consumption by adjusting the sympathetic nervous system or leptin sensitivity. The study of how specific neurons such as AgRP regulate energy metabolism will provide an important theoretical basis for the discovery of the etiology and treatment of obesity.

Postdoc DENG Jia-li and Ph.D. student FEI Fei used inducible gene knockout techniques to specifically knock out ATF4 in AgRP neurons of adult mice under the guidance of Guo, finding that these mice were thinner with insulin sensibility and leptin sensibility improved. At the same time, the experimental mice reduced food intake and increased energy consumption, improving the body heat. After high-fat diet, ATF4 mice with AgRP-specific knockout were resistant to high-fat-induced obesity, insulin resistance and fatty liver. Further study of its mechanism of action found that ATF4 can be combined with the promoter of FOXO1 to directly regulate its expression. After injection of FOXO1 adenovirus in the arcuate nucleus of the hypothalamus of the knockout mice, the fat content of mice significantly increased.

In summary, the study found the important function of ATF4 in the hypothalamic AgRP neurons to regulate energy balance and lipid metabolism, suggesting that the treatment of obesity and metabolic diseases, ATF4 may become a new drug target. Flarebio provides you with high-quality recombinant proteins like recombinant PIGR at competitive prices.