A new study in the Journal of Biological Chemistry shows how a molecular chain of events in the brains of obese rats undermines their ability to suppress appetite and to increase calorie burning.
The Brown University researchers behind the discovery describe it as a vicious cycle, involving a breakdown in how brain cells process key proteins, that allows obesity to beget further obesity.
For the study, the researchers fed some rats a high-calorie diet and fed others a normal diet for 12 weeks. The overfed rats developed the condition of "diet-induced obesity." The team then studied the hormone levels and brain cell physiology of the rats. They also tested their findings by experimenting with the biochemistry of key individual cells on the lab bench.
They found that in the obese rats, a key "machine" in the brain cells' assembly line of protein-making, called the endoplasmic reticulum (ER), becomes stressed and overwhelmed. The overloaded ER "fumbles" the proper handling of an important enzyme called PC2. The PC2 levels they measured in obese rats were 53 percent lower than in normal rats.
By laying out the exact mechanism responsible for why the brains of the obese rats failed to curb appetite or spur greater calorie burning, the study points drug makers to several opportunities where they can intervene to break this vicious cycle and fix the core protein-processing problem that allows obesity to perpetuate itself.
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Source: Brown University