September 23, 2019

We all know that proper diet and exercise are supposed to help us maintain a healthy weight. But in some cases, genetics may make it incredibly difficult to keep excess fat away.

Texas Biomed researcher Raul Bastarrachea, MD, and the team at Southwest National Primate Research Center (SNPRC) recently set out to discover why exactly some people are naturally inclined toward obesity. In the process, they found a mutation that affects leptin — a protein produced by fat cells that travels to the brain and signals to the body that there is enough fat and no more food is needed.

Simply put, leptin is a hunger suppressor.

In the study, Bastarrachea and team examined the case of two sisters in Colombia who started their lives as normal-weight babies but who quickly experienced childhood-onset severe obesity. Both were found to have a mutation in the leptin gene on chromosome 7, causing their leptin levels to be so low they were below the detection limit of the manufactured test kit.

The gene mutation forced the leptin proteins to be “misfolded,” rendering them ineffective and destroying their function.

When researching the genetics of the family, scientists noted these women were children of lineal consanguinity, which means several generations before them married blood relatives. This is a common practice in about a fifth of the world population, mostly in the Middle East, West Asia and North Africa, and increases health risks for children of these unions, including rare diseases caused by recessive genes.

Bastarrachea noted a greater understanding of this mutation and its causes is another step toward fighting global obesity.

“We keep learning more and more about the role of fat in normal-weight people,” he noted. “By researching what goes wrong when genes don’t code correctly for the production of leptin, we are coming closer to answers that could help millions of people with metabolic disorders.”

To help get those answers, the SNPRC is looking at obesity within its nonhuman primate (NHP) colony. 

“Fortunately, we have less than 5% obesity in our 2,500 NHPs and an even lower rate of diabetes at 1.5%, due to the low-carb Purina chow they eat and the activity they display given the comfortable size of their housing,” said Bastarrachea. 

Occasionally, a few of SNPRC’s baboons may experience excessive growth leading to excess body fat. 

“We speculate these animals may have particular gene mutations that mimic the extreme obese phenotype of the few individuals reported in scientific literature. We consider our baboon subgroup a valuable model of extreme obesity given NHPs share up to 98% genetic similarities with humans, thus allowing obesity study results in NHPs to be easily translated to humans,” Bastarrachea concluded. 

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