Loss of βENaC Prevents Hepatic Steatosis but Promotes Abdominal Fat Deposition Associated with a High-Fat Diet

Degenerin proteins, such as Acid-Sensing Ion Channel 2 (ASIC2) and β Epithelial Na⁺ Channel (βENaC), have been implicated in cardiovascular function. We previously demonstrated that mice lacking normal levels of βENaC and ASIC2 are protected from diet-induced obesity, metabolic disruption, and hepatic steatosis.

To investigate the specific role of βENaC proteins in the progression of metabolic disease, we examined the impact of a high-fat diet (HFD) in the βENaC hypomorph mouse model (βMUT). Body composition and metabolic and behavioral phenotypes were examined in male and female and βMUT and WT mice (n = 6-14/group) fed a normal chow diet (NFD) from weaning until 16 weeks of age, then a 60% kcal-fat diet for 5 weeks.

Compared to WT mice, βMUT male mice have reduced lean and total body mass. No remarkable differences in energy expenditure, motor activity, or food consumption patterns were detected. HFD-fed male βMUT mice exhibited reduced liver fat content (mass and Oil Red O staining) yet increased abdominal fat depots. HFD-fed female βMUT mice exhibited lower heart mass.

These novel findings suggest a role for βENaC in the maintenance of metabolic homeostasis and adipose tissue distribution.