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Understanding how obese fat cells work

In obese individuals, fat cells are bloated and inflamed because they receive too many nutrients, including lipids. In these cells, various components cannot work properly anymore and, instead, they activate new proteins to cope with the situation. One of the most challenged organelles in obese fat cells is a maze-like compartment called the endoplasmic reticulum (ER) that makes proteins and lipid droplets and senses the amount of nutrients that enter the cell. Margaret F. Gregor and Gokhan S. Hotamisligil review current knowledge about how the ER works in fat cells and is modified in obesity. They show that when a fat cell receives too many nutrients, the ER is overwhelmed and triggers a process called the unfolded protein response (UPR). This process is one of many cellular responses that activate proteins that increase inflammation and can even result in the death of the cell. UPR also causes insulin resistance, a condition in which the production and function of insulin a hormone produced by the pancreas is impaired and blood sugar is too high. The scientists show that by better understanding how the ER works, it may be possible to devise a therapy that enhances the function of the ER and maybe improve the health of obese people. Already, two molecules that protect the ER from obesity-related stress have shown some success in mice. Called PBA and TUDCA, the molecules decreased blood sugar and insulin levels and improved overall response to insulin production.


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