Scientists reveal new mechanisms for cholesterol synthesis regulation

Insulin and glucose raise cholesterol synthesis through the mTORC1-USP20-HMGCR path pathline
On November 11, Song Baoliang, a professor at Wuhan University's School of Life Sciences, published a paper in Nature, "Eating induces cholesterol synthesis through the mTORC1-USP20-HMGCR pathline", revealing the regulatory mechanism for the increase in cholesterol synthesis induced by eating. This study helps to understand the laws of cholesterol metabolism in the body and lays the foundation for the treatment of metabolic diseases such as hyperlipidemia, obesity, fatty liver disease and diabetes.
cholesterol is a key component of the cell membrane, but high concentrations can easily lead to cardiovascular disease. The body can take cholesterol from foods such as meat and eggs, however, in the case of carbohydrate-based foods, cholesterol is mainly dependent on its own synthesis. Cholesterol synthesis requires a lot of nutrients and energy, so over time, mammals have evolved to significantly increase cholesterol synthesis only after eating, while in hunger it inhibits synthesis, a regulatory mechanism that has been unknown.
study by Song Baoliang's team found that the speed-limiting enzyme in the cholesterol synthesis pathway, hydroxymethyl diamide coenzyme A reductase (HMGCR), increased significantly after eating. They used cleverly designed in vitro bio-chemical experiments combined with expression screening and animal models to demonstrate that elevated glucose and insulin after eating led to the phosphorylation modification of the USP20 protein, which stabilizes HMGCR and encourages the body to convert absorbed nutrients into cholesterol, which is necessary for life activities.
Subsequently, the researchers found that inhibiting USP20 activity in a long-term, high-sugar, high-fat diet significantly reduced cholesterol, triglyceride levels, reduced weight, lower body fat, and increased insulin sensitivity; And these improved metabolic indicators are helpful in the treatment of related metabolic diseases.
it is learned that Lu Xiaoyi, associate professor Shi Xiongjie, doctoral students Hu Ao and Wang Juqiong are co-authors of the paper and Song Baoliang is the author of the communication. Ding Yi, Ph.D., Jiang Wei, Ph.D., Sun Ming, Associate Professor Zhao Xiaoxuan and Luo Wei, and Professor Qi Wei of Shanghai University of Science and Technology are co-authors. (Source: Wen Caifei, China Science Journal)
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