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Mice lacking ASIC2 and βENaC are protected from high-fat-diet-induced metabolic syndrome
Madison Hamby1, David E Stec1, Emily Hildebrandt1
1Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States.
Introduction:
Degenerin proteins, such as βENaC and ASIC2, have been implicated in cardiovascular function. However, their role in metabolic syndrome have not been studied. To begin to assess this interaction, we evaluated the impact of a high fat diet (HFD) on mice lacking normal levels of ASIC2 (ASIC2-/-) and βENaC (βENaCm/m).
Methods:
Twenty-week-old male and female mice were placed on a 60% HFD for 12 weeks. Body weight was measured weekly, and body composition by non-invasive ECHO MRI and fasting blood glucose were measured at 0, 4, 8 and 12 weeks. A glucose tolerance test was administered after 12 weeks. Differences between ASIC2-/-/βENaCm/m and WT groups were compared using independent t-tests or ANOVA where appropriate within each sex. Data are presented as mean ± SEM and ASIC2-/-/βENaCm/m vs. WT.
Results:
At 20 weeks of age, ASIC2-/-/βENaCm/m mice (n=9F/10M) weighed less and gained less weight than WT (n=12F/16M). Total body fat and lean body masses were reduced in female and male ASIC2-/-/βENaCm/m mice. Total body fat and lean body masses as % control were identical at the end of 12 weeks. Fasting blood glucoses were lower in female and male ASIC2-/-/βENaCm/m vs. WT mice after 12 weeks HFD. The area under the curve for the glucose tolerance test was reduced in female and tended (p=.079) to decrease in male ASIC2-/-/βENaCm/m. Plasma leptin and insulin were reduced in female and male ASIC2-/-/βENaCm/m vs. WT mice. Plasma insulin in female ASIC2-/-/βENaCm/m mice remained unchanged throughout the HFD period. Liver and liver fat masses, as well as percent liver fat, were reduced in both female and male ASIC2-/-/βENaCm/m mice after HFD. Plasma triglycerides, cholesterol, LDL- and HDL-cholesterols were markedly improved in male and/or female ASIC2-/-/βENaCm/m following the HFD.
Discussion:
These novel findings suggest that loss of ASIC2 and βENaC offer a significant protection against HFD-induced metabolic syndrome.
Insights
Mice lacking degenerin proteins ASIC2 and βENaC show reduced weight gain and improved metabolic markers when fed a high-fat diet. These findings suggest a protective role for ASIC2 and βENaC in preventing diet-induced metabolic syndrome.
Area of Science:
- Cardiovascular Research
- Metabolic Syndrome Studies
- Ion Channel Function
Background:
- Degenerin proteins, including βENaC and ASIC2, are known to influence cardiovascular function.
- The specific role of these proteins in the development of metabolic syndrome remains largely uninvestigated.
Purpose of the Study:
- To investigate the impact of a high-fat diet (HFD) on mice with altered levels of ASIC2 and βENaC.
- To assess the potential protective effects of ASIC2 and βENaC deficiency against diet-induced metabolic disturbances.
Main Methods:
- Male and female mice lacking ASIC2 (ASIC2-/-) and βENaC (βENaCm/m) were subjected to a 60% HFD for 12 weeks.
- Body weight, body composition (ECHO MRI), fasting blood glucose, and glucose tolerance were monitored.
- Differences between knockout and wild-type (WT) groups were analyzed using statistical tests.
Main Results:
- ASIC2-/-/βENaCm/m mice exhibited reduced body weight, weight gain, and adiposity compared to WT controls.
- Fasting blood glucose levels and glucose tolerance tests indicated improved glucose metabolism in knockout mice.
- Lipid profiles, including triglycerides and cholesterol, were significantly improved, and liver fat content was reduced in ASIC2-/-/βENaCm/m mice.
Conclusions:
- Loss of ASIC2 and βENaC function confers significant protection against high-fat diet-induced metabolic syndrome.
- These findings highlight a novel role for degenerin proteins in metabolic health and disease.
