October 2019

The current epidemic of obesity is a major contributing factor in the rising rate of type 2 diabetes. Recent work from the laboratory of Kamal Rahmouni, PhD, a member of the Fraternal Order of Eagles Diabetes Research Center (FOEDRC), uncovered a novel and important role for a protein complex called the BBSome in the function of key nerve cells called neurons in small a part of the brain known as the hypothalamus that controls food intake, body’s fat and glucose metabolism. POMC and AgRP neurons  in the hypothalamus play an essential role in the regulation of body weight by regulating appetite and energy expenditure (fat burning).

Dr. Rahmouni and his team published an important paper this month in which they showed that by genetically disrupting the BBSome in these defined neurons causes severe obesity associated with elevated insulin levels in the blood and abnormal glucose metabolism. Their investigation of the biochemical pathway that links the BBSome to control of metabolism led them to the identification of a defect in the transport of specialized receptors (G protein-coupled neuropeptide Y Y2 receptor (NPY2R) and serotonin 5-hydroxytryptamine (HT)2C receptor (5-HT2CR)) to the cell surface of these neurons and specialized structures in these cells known as cilia. These receptors interact with hormones and other signals that underlie neural control of metabolism. One of the receptors affected by loss of the BBSome is the target of BELVIQ®, an FDA-approved prescription weight-reducing medication. These findings are important because it shows that obese people who do not respond to weight-reducing medications such as BELVIQ® may have or develop defects in this pathway, which influences in the way the brain responds to this weight loss treatment.

Dr. Rahmouni’s paper, entitled: “The BBSome in POMC and AgRP Neurons Is Necessary for Body Weight Regulation and Sorting of Metabolic Receptors”, which acknowledged FOEDRC support of this work, was published in the prestigious journal Diabetes.