Obesity and obesity-related diabetes and heart disease affect nearly half of adults in the United States. One potential solution to alleviate its prevalence may lie in finding ways to increase metabolism.

With a five-year $1.93M R01, Renata Pereira, PhD, research assistant professor in Endocrinology and Metabolism, and a team of researchers plan to investigate methods to increase metabolism in brown fat cells. Brown fat cells burn calories and produce heat when the body is exposed to cold temperatures, and past studies have suggested brown fat cells can therefore speed up metabolic activity. In Pereira’s past studies, mouse models have demonstrated that brown fat cells are triggered when exposed to cold temperatures for a brief period of time, inducing a reaction called the integrated stress response (ISR).

“The ISR seems to induce the release of hormones that improve the body’s metabolism, helping the mice burn calories more efficiently,” Pereira said.

Pereira found that one of these hormones induced by the ISR is the growth differentiation factor 15 (GDF15). When Pereira genetically omitted a critical protein in brown fat cells called optic atrophy 1 (OPA1), the ISR response and secretion of GDF15 occurred even at room temperature. In her new studies, she proposes to investigate whether GDF15 promotes leanness in mice deficient for OPA1 in brown fat cells.

“As a result (from genetically removing the OPA1 protein), these mice had faster metabolism and were resistant to obesity and diabetes, even when consuming a diet very high in fat,” Pereira said. “We believe that the ISR in fat cells can be brought about by either cold temperatures or OPA1 deletion in a similar manner. Completion of this project will reveal the mechanisms underlying ISR activation and the role of the ISR and GDF15 in brown fat cells, potentially leading to new ways to combat obesity and associated disorders in humans.”