■退化素蛋白,如βENaC和ASIC2,与心血管功能有关。然而,它们在代谢综合征中的作用尚未被研究。为了开始评估这种互动,我们评估了高脂饮食(HFD)对缺乏正常水平ASIC2(ASIC2-/-)和βENaC(βENaCm/m)的小鼠的影响.
将20周龄的雄性和雌性小鼠置于60%HFD上12周。每周测量体重,在0、4、8和12周时通过非侵入性ECHOMRI测量身体成分和空腹血糖。12周后进行葡萄糖耐量试验。ASIC2-/-/βENaCm/m和WT组之间的差异使用独立的t检验或ANOVA(适当时在每个性别内)进行比较。数据以平均值±SEM和ASIC2-/-/βENaCm/mvs.WT.
■在20周龄时,ASIC2-/-/βENaCm/m小鼠(n=9F/10M)比WT(n=12F/16M)体重更轻,体重增加更少。雌性和雄性ASIC2-/-/βENaCm/m小鼠的总脂肪和瘦体重减少。在12周结束时,作为%对照的总身体脂肪和瘦身体质量相同。女性和男性ASIC2-/-/βENaCm/m的空腹血糖较低。WT小鼠在12周后HFD。葡萄糖耐量试验的曲线下面积在女性中减少,而在男性ASIC2-/-/βENaCm/m中趋于减少(p=0.079)。女性和男性ASIC2-/-/βENaCm/m的血浆瘦素和胰岛素降低WT小鼠。雌性ASIC2-/-/βENaCm/m小鼠的血浆胰岛素在整个HFD期间保持不变。肝脏和肝脏脂肪块,以及肝脏脂肪的百分比,在HFD后,雌性和雄性ASIC2-/-/βENaCm/m小鼠均降低。血浆甘油三酯,胆固醇,HFD后,男性和/或女性ASIC2-/-/βENaCm/m的LDL-和HDL-胆固醇显着改善。
■这些新发现表明,ASIC2和βENaC的缺失对HFD诱导的代谢综合征提供了显著的保护作用。
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: These novel findings suggest that loss of ASIC2 and βENaC offer a significant protection against HFD-induced metabolic syndrome.