Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States.
Department of Chemistry, Vanderbilt University, Nashville, TN, United States.
Front Endocrinol (Lausanne). 2024 Aug 19;15:1449344. doi: 10.3389/fendo.2024.1449344. eCollection 2024.
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 (βENaC).
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/βENaC and WT groups were compared using independent t-tests or ANOVA where appropriate within each sex. Data are presented as mean ± SEM and ASIC2/βENaC vs. WT.
At 20 weeks of age, ASIC2/βENaC 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/βENaC 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/βENaC 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/βENaC. Plasma leptin and insulin were reduced in female and male ASIC2/βENaC vs. WT mice. Plasma insulin in female ASIC2/βENaC 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/βENaC mice after HFD. Plasma triglycerides, cholesterol, LDL- and HDL-cholesterols were markedly improved in male and/or female ASIC2/βENaC following the HFD.
These novel findings suggest that loss of ASIC2 and βENaC offer a significant protection against HFD-induced metabolic syndrome.
退行性蛋白，如βENaC 和 ASIC2，已被牵连到心血管功能中。然而，它们在代谢综合征中的作用尚未被研究。为了开始评估这种相互作用，我们评估了高脂肪饮食（HFD）对缺乏正常水平 ASIC2（ASIC2）和βENaC（βENaC）的小鼠的影响。
20 周龄雄性和雌性小鼠接受 60%HFD 喂养 12 周。每周测量体重，通过非侵入性 ECHO MRI 和空腹血糖测量身体成分，并在 0、4、8 和 12 周时进行空腹血糖耐量试验。使用独立 t 检验或适当的方差分析比较 ASIC2/βENaC 和 WT 组之间的差异。数据以平均值±SEM 表示，并与 WT 进行 ASIC2/βENaC 比较。
在 20 周龄时，ASIC2/βENaC 小鼠（n=9F/10M）的体重和体重增加均低于 WT（n=12F/16M）。雌性和雄性 ASIC2/βENaC 小鼠的总体脂肪和瘦体质量减少。12 周后，雌性和雄性 ASIC2/βENaC 小鼠的总体脂肪和瘦体质量与对照的百分比相同。12 周 HFD 后，雌性和雄性 ASIC2/βENaC 小鼠的空腹血糖降低。雌性和雄性 ASIC2/βENaC 的葡萄糖耐量试验的曲线下面积减少，并且倾向于（p=.079）减少。雌性和雄性 ASIC2/βENaC 小鼠的血浆瘦素和胰岛素减少。雌性 ASIC2/βENaC 小鼠的血浆胰岛素在整个 HFD 期间保持不变。雄性和/或雌性 ASIC2/βENaC 在 HFD 后，肝和肝脂肪量以及肝脂肪百分比降低。雄性和/或雌性 ASIC2/βENaC 的血浆甘油三酯、胆固醇、LDL-和 HDL-胆固醇明显改善。
这些新发现表明，ASIC2 和βENaC 的缺失为 HFD 诱导的代谢综合征提供了显著的保护。
