(LB02-22-25) Adipose Cyp27a1 Deletion in Mice Alters Basal Metabolic Rate and Insulin Metabolism

Objectives: Understand the role of CYP27a1 in adipose tissue and it's metabolic effects under dietary stress, specifically in the insulin metabolism.

Methods: Our lab developed an adipose-specific Cyp27a1 KO. Preadipocytes isolated from these mice exhibited impaired differentiation compared to wild type mice, as well as lower BA levels in WAT. To continue analyzing this model, 15-17 weeks-old mice underwent insulin and glucose tolerance tests (ITT and GTT respectively), followed by a basal metabolic rate analysis using a comprehensive lab animal monitoring system (CLAMS). Mice were sacrificed and liver, AT, serum, and muscle were collected.

Results: After differentiation, preadipocytes isolated from murine white AT (WAT) highly express Cyp27a1 compared to Cyp7a1, a regulatory gene in the classical pathway for BA synthesis, 20 times fold. A global Cyp27a1 KO model showed lower BA concentration in WAT and limited differentiation ability in WAT preadipocytes compared to wild-type (WT) mice. Our pilot finding show that loss of Cyp27a1 gene in adipose tissue alters glucose levels in glucose and insulin tolerance test, as well as basal energy metabolism analyzed through CLAMS.

Conclusions: Loss of adipose Cyp27a1 gene alters glucose tolerance and energy expenditure, indicating novel role for this pathway in the adipose milieu.

Funding Sources: National Institutes of Health
Consejo Nacional de Humanidades, Ciencias y Tecnologías de Mexico