Decreasing ceramides reduced obesity, insulin resistance in mice

Thermogenic adipocytes are specialized cells capable of converting chemical energy into heat and regulating body temperature. However, aging and weight gain can deplete thermogenic adipocytes and increase insulin resistance. Bhagirath Chaurasia, PhD, assistant professor in Endocrinology and Metabolism, aimed to determine the mechanisms behind this correlation in a study recently published in Molecular Metabolism.

“Thermogenic adipocyte quantity and activity inversely correlate with age and adiposity, leading investigators to speculate that disruption of thermogenic adipocytes activity may contribute to the obesity epidemic,” Chaurasia said.

Chaurasia’s study focused specifically on the lipid metabolites known as ceramides, which accumulate as a result of aging and obesity. Chaurasia hypothesized that ceramides might impair the thermogenic adipocyte metabolic processes. 

In mouse models, Chaurasia found that depletion of ceramide synthesis in thermogenic adipocytes lead to improved glucose homeostasis and diet-induced obesity. Conversely, degradation of ceramide depletion in thermogenic adipocytes lead to accumulation of ceramide, diminished energy production, and obesity.

“These studies reveal that implementation of therapeutic strategies to lower ceramides may serve as a means of improving thermogenic adipocyte health to combat obesity and cardiometabolic disease,” Chaurasia said.

Chaurasia, a member of the Fraternal Order of Eagles Diabetes Research Center, is a relatively recent arrival at Iowa. His work on this study was completed with several other researchers at the University of Utah, including Li Ying, Chad Lamar Talbot, John Alan Maschek, James Cox, William L. Holland, and Scott A. Summers. Edward H. Schuchman of the Mount Sinai School of Medicine and Yoshio Hirabayashi of the RIKEN Brain Science Institute in Wako-Shi, Saitama, Japan, also contributed.