The New Direction of Fat Burning and Weight Loss
On October 27, 2021, researchers from the University of California, San Diego published a research paper titled: Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes in the top international academic journal Nature. The study discovered a previously unknown metabolic pathway that involves the accumulation and degradation of glycogen, which can regulate the energy consumption and caloric production of fat cells. This discovery links sugar metabolism with adipose tissue heat production, and may provide new ideas for the treatment of obesity, type 2 diabetes and other metabolic diseases. Humans have at least two types of adipose tissue-white adipose tissue (WAT) and brown adipose tissue (BAT). White fat cells are essentially inert energy containers, storing energy in the form of single large oil droplets. Brown fat cells are more complex, containing multiple smaller droplets that are mixed with dark mitochondria, the "engines" that convert fat droplets into heat and energy.
In recent years, people have been trying to find ways to increase the activity of brown or beige fat cells to induce fat cells to burn fat droplets and generate heat, as a means of treating obesity, type 2 diabetes and other diseases. Unfortunately, the therapeutic potential of brown/beige fat cells has been hampered due to the complexity of the process involved. It was not even confirmed that there are active brown fat cells in healthy adults until 2009. Before that, it was thought that they were only common in newborns.
In this new study, the research team reported a surprising new discovery that glycogen metabolism plays a key role in the regulation of inguinal white adipose tissue (iWAT) browning. iWAT stimulates the production of heat in fat cells through sympathetic nerve activation. Accompanied by the coordinated up-regulation of glycogen metabolism genes, it leads to the dynamic accumulation and turnover of glycogen in these cells. Not only that, the researchers also found that in two independent obese people, the expression of these genes in adipose tissue was also negatively correlated with obesity. In addition, glycogen synthesis and degradation are necessary for fat cell browning, including β-adrenergic agonist injection, long-term cold exposure, and the beneficial metabolic effects of catecholamines in obesity. In addition, glycogen synthesis and conversion ensure that only white fat cells have sufficient energy to provide thermogenic fuel, thus preventing the potential toxic effects of ATP uncoupling resulting from UCP1 expression. That is, cells can be safely "decoupled", and the energy released is not used to produce ATP, which is the "energy currency", but only to produce heat.
What's more, stronger glycogen metabolism was associated with fat burning and weight loss in obese mice. These findings suggest that regulating glycogen metabolism in fat cells may help treat obesity. More specifically, the decoupling mechanism described in the study facilitates weight loss and promotes overall improvement in metabolic health. In human history, there is a banned weight loss drug-2,4-dinitrophenol (DNP), which uses uncoupling to quickly consume body energy to achieve the goal of weight loss. However, the terrible thing is that the uncoupling effect of DNP is uncontrollable, and long-term use of DNP will lead to serious organ damage and endanger life.
Professor Alan Saltiel, the corresponding author of the paper, said: " Decoupling is an important way to generate heat. In this process, the reserve energy of cells is not used to produce ATP, but only to produce heat. Therefore, this approach must ensure that it only occurs in fat cells with sufficient energy reserves. " All in all, this study found that the process of glycogen metabolism plays a key role in the "browning" process of white adipose tissue. The accumulation and degradation of glycogen can regulate the energy consumption and calorie production of fat cells. This provides a new research direction for the treatment of obesity, type 2 diabetes and other metabolic diseases!
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