The Chaurasia Lab, led by Bhagirath Chaurasia, MSc, PhD, assistant professor in the Division of Endocrinology & Metabolism and member of the FOEDRC, has continued to explore emerging targets to reduce obesity and treat metabolic conditions. Their recent publication, “Ceramide-induced FGF13 impairs systemic metabolic health,” appears in Cell Metabolism and contributes to the group’s history of groundbreaking research in the field.

The lab had previously found that fatty lipids called ceramides are a detriment to metabolic health due to their damaging effect on adipocytes’ ability to efficiently store and utilize nutrients. As such, ceramides are involved in a variety of cellular and systemic metabolic issues, and targeting enzymes required for ceramide synthesis offers a path to their improvement while minimizing unintended effects. “Despite these exciting advances, we wondered whether we could identify ceramide effectors that could be targeted to improve metabolic health without altering ceramide levels, opening the door to novel therapies,” said Chaurasia.

In this recent work, the Chaurasia Lab identifies fibroblast growth factor FGF13’s as an effector of ceramide. This new publication in the high-impact Cell Metabolism emphasizes the importance of their findings; although FGF13 has been previously studied in relation to conditions such as cardiac arrhythmias, neurological diseases, and cancers, its role in these metabolic diseases has not been significantly explored.

During their study, the researchers noted obesity-induced FGF13 expression in adipose tissue in both mice and humans, and that this expression was positively associated with glycemic indices seen in Type 2 diabetes. FGF13 exhibits its detrimental effects on metabolic functions by “inhibiting mitochondrial content and function, metabolic elasticity, and caveolae formation, which cumulatively impairs glucose utilization and thermogenesis,” indicating that treatment and prevention for some metabolic diseases, including diabetes, could lie in inhibiting FGF13.

In adult obese and insulin-resistant mice, ablation of FGF13 showed improved insulin sensitivity and resolved excessive fat accumulation in the liver. Further, these methods appear to improve energy and glucose homeostasis without altering ceramide levels. These results show great promise for future research; metabolic diseases are often chronic, complex, and disproportionately impact individuals of lower socioeconomic status. A better understanding of FGF13, and ceramides, presents an opportunity to reduce their effects by making specialized therapies more accessible.

“The identification of FGF13 as a ceramide target provides an additional approach of targeting ceramide pathway for the treatment of metabolic diseases,” Jamal Naderi, PhD, said. Naderi and Himani Thakkar, PhD, share lead authorship on this publication.

Chaurasia would like to thank all the members of his lab, and especially to acknowledge Naderi and Thakkar for their dedication and collaboration.