Protein-coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex-dependently in rats.

ABSTRACT:

Objective

Adenylate cyclase 3 (Adcy3) has been linked to both obesity and major depressive disorder. We identified a protein-coding variant in the transmembrane (TM) helix of Adcy3 in rats; similar obesity variants have been identified in humans. This study investigates the role of a TM variant in adiposity and behavior.

Methods

We mutated the TM domain of Adcy3 (Adcy3^mut/mut) and created a heterozygous knockout (Adcy3^+/-) in Wistar Kyoto (WKY) rats. Wild-type, Adcy3^+/-, and Adcy3^mut/mut rats were fed a high-fat diet for 12 weeks. We measured body weight, fat mass, glucose tolerance, food intake, metabolism, emotion-like behaviors, memory, and downstream proteins.

Results

Adcy3^+/- and Adcy3^mut/mut rats

SUBMITTER: Fitzpatrick MK 

PROVIDER: S-EPMC12247540 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature