What used to help you withstand famine now makes you stock up on fat

, but at a time when overnutrition is common, ancient genetic mutations put modern people at higher health risks.
October 14th, a study published online in Cells found the key to change, all closely related to a non-coding small molecule RNA (microRNA).small RNA is a sequence of 20-24 nucleotides, a single small RNA can participate in the regulatory expression of one or more genes.Wang Lifeng, the first author of the
paper, told China Science that in his previous work, he and his co-author Anders Naar, a former Harvard Medical School professor, screened several small RNAs associated with metabolic diseases such as obesity and diabetes.
" Although we screened several small RNAs in samples of nearly 20,000 metabolic patients at the time, it is not clear whether these small RNAs are directly related to metabolic diseases and human evolution. Wang Lifeng said.
the newly released work, Wang Lifeng is a researcher at Harvard Medical School and the Center for Oncology at Massachusetts General Hospital. Currently, he works in drug screening for cardiovascular diseases at Johnson and Johnson, where he is now the director of the Department of Metabolism at the University of Berkeley.
the new online study, Wang Lifeng et al. screened out one of the small RNAs: miR-128-1, and observed a series of regulatory roles in the body's metabolism.
interestingly, through genome-wide correlation studies, the team found that this small RNA is located in the hot area of evolutionary natural selection: 2q21.3.
this group of genes, there is the well-known Lactase gene (Lactase gene), or LCT, whose active expression encourages people to produce large amounts of enzymes that help digest lactose and get nutrients from milk. In animal-specific studies, researchers also found more than one gene that promotes fat accumulation in 2q21.3.
"In humans, especially in Europe, 2q21.3 mutates and has a higher chance of being inherited," Wang said.
now, things have changed. New research shows that miR-128-1 also plays an important "saving" role in the 2q21.3 gene group , which allows the body to consume less energy and hoard more fat.new study, scientists have discovered small RNAs located in areas popular for natural selection, which play a key role in metabolism regulation. Photo Source: CellThe mutation of the 2q21.3 gene in the human body dates back about 7,000 years, when humans were still hunting to survive and more vulnerable to famine. New research suggests that miR-128-1's "frugal" properties may have made ancient humans more likely to survive, making 2q21.3 a highly chosen genomic region in evolution.
7,000 years later, however, people are sedentary and overnourished, and the effects of miR-128-1 are more likely to link people to metabolic disorders such as obesity and diabetes.
"This is interesting in this study, miR-128-1, a small RNA associated with metabolic disease, which is also associated with human evolution." Wang Lifeng said.
, the team presented more evidence of miR-128-1's involvement in metabolic regulation.miR-128-1 was involved in metabolic regulation in mice. In the
experiment, the researchers modeled genetically obese mice with metabolic disorders and a lack of leptin, who showed a significant appetite for leptin deficiency. While providing mice with a high-fat diet, the researchers injected them with drugs targeted at miR-128-1 at a fixed number and dose per week, invalidated the small RNA.
results showed a significant decrease in miR-128-1 levels in major metabolic tissues such as liver and brown fat in mice injected with the drug. After 2 weeks of treatment, the mice who ate high-fat feed had significantly lower body weight and fat content and faster energy consumption without losing food.
researchers also performed knock-out treatment on miR-128-1 in another group of mice, and found that after 12 weeks of continuous high-fat diet, the white adipose tissue in the mice was more than 60 percent lower than in the control group, and their energy consumption increased significantly, with better response to insulin and glucosaccharin stabilization.
, they also observed a decrease in liver inflammation and expression of fat-producing markers in mice. "These have shown that miR-128-1 plays an important metabolic regulatory role in obese mice." Introduction by Wang Lifeng.
Finally, based on the experimental results of mouse models and human genome-wide association research data, Wang Lifeng et al.'s research confirmed the regulatory role of miR-128-1 in metabolism: high levels of miR-128-1 in metabolic tissue may reduce the body's energy consumption and promote the accumulation of fat in the human body.
time, the small RNA that helped ancient humans endure famine increased the risk of metabolic disease in modern humans. However, this also provides researchers with new treatment ideas.
"Current treatments for obesity and type 2 diabetes are mostly focused on proteins, and our latest study suggests that non-coded RNA may also be a target. However, these have yet to be further verified. Wang Lifeng said. (Source: Ren Fangyan, China Science Journal)
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