May 2021

Obesity has reached epidemic proportions in the US and around the world. This is a problem because being obese increases the likelihood of developing serious medical problems such as type 2 diabetes, high blood pressure and cardiovascular diseases such as heart attacks and heart failure. Obesity also increases the risks of complications from COVID-19 infections. We still do not understand all of the reasons why obesity develops and why some people develop complications and others do not. In work recently published in the Journal Molecular Metabolism, FOEDRC member Dr. Kamal Rahmouni, PhD, professor of Neuroscience, Pharmacology, and Internal Medicine, in collaboration with FOEDRC colleagues at the University of Iowa, identified a protein complex, called the BBSome. These are present in neurons (nerve cells) in a part of the brain called the hypothalamus. The hypothalamus is a small area in the brain that determines whether the calories derived from the food we eat is burned or stored in the form of fat. The BBsome in these nerve cells regulate body fat and development of obesity. Dr. Rahmouni’s team found when the BBSome was removed from neurons of the hypothalamus, animals progressively increased body fat and weight resulting in obesity. This is due to inability of the hypothalamus to properly send signals to peripheral tissues that burn calories. As a result, these animals had lower metabolic rates as indicated by reduced energy expenditure. Because of this, their bodies were burning less calories than they should. Therefore, most of the ingested calories were directed to the fat tissues for storage, which increased the mass of fat tissue leading to obesity. These findings indicate that defects in the BBSome could be a potential cause of obesity. Very interestingly, the obesity that resulted from absence of the BBSome in the hypothalamus did not lead to diabetes, insulin resistance or high blood pressure. These findings are very similar to what is seen in a small subset of obese humans, referred to as “healthy obese,” who do not develop type 2 diabetes and cardiovascular diseases. The Rahmouni group is now conducting follow up studies to further understand what confers this remarkable protection against obesity-related conditions. Answering this question will reveal how metabolic and cardiovascular disease develop in obesity and may lead to more specific ways to treat these complications, particularly in individuals who struggle to lose weight.

Rouabhi M, Guo DF, Morgan DA, Zhu Z, López M, Zingman L, Grobe JL, Rahmouni K.. BBSome Ablation in SF1 Neurons Causes Obesity without the Comorbidities. Mol Metab. 2021 Mar 12:101211. doi: 10.1016/j.molmet.2021.101211. Epub ahead of print. PMID: 33722691.