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Sex‐dependent protection from high fat diet‐induced metabolic disease in mice lackingDegenerin proteins
Author(s) -
Drummond Heather,
Mitchell Zachary,
Hildebrandt Emily,
Stec David E
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.592.3
Subject(s) - medicine , endocrinology , epithelial sodium channel , trpc6 , receptor , chemistry , biology , transient receptor potential channel , sodium , organic chemistry
Degenerin proteins, such as βENaC and ASIC2, and Transient Receptor Potential Channel 6 (TrpC6) have been implicated in cardiovascular function. However, their roles and potential interaction in metabolic disease has not been studied. To begin to assess this interaction, we evaluated the impact of a high fat diet (HFD) on in mice lacking normal levels of ASIC2, βENaC and TrpC6. Twenty week old male and female mice were placed on a 60% HFD for 12 weeks. Body weight was measured weekly, 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/TrpC6 and WT groups were compared using independent t‐tests within each sex. Data are presented as mean ± SEM, ASIC2/βENaC/TrpC6 vs. WT. At 20 weeks of age, female ASIC2/βENaC/TrpC6 mice (n=6) weighed less (22.7±1.0 vs 26.3±0.8g, p=0.029) and gained less weight (12.1±1.7 vs. 20.5±1.3g, p=0.004) than WT (n=5). Total body fat (16.2±2.0 vs 23.2±1.1g, p=0.017) and lean body masses (19.2±1.0 vs 24.8±0.7, p=0.0014) were reduced in female ASIC2/βENaC/TrpC6 mice. In contrast, male ASIC2/βENaC/TrpC6 (n=5) mice had similar body weight (34.1±0.8 vs. 36.8±1.8g, p=0.165) at 20 weeks and 12 week HFD weight gain (11.8±1.5 vs. 12.1±0.9g, p=0.881) compared to WT (n=4). Fasting blood glucoses were lower in female (166±6.4 vs.212±5.3 mg/dL, p=0.0004) and male (181±2.8 vs.210±9 mg/dL, p=0.006) ASIC2/βENaC/TrpC6 mice after 12 weeks HFD. The area under the curve for the glucose tolerance test was reduced in female (18263 ± 510 vs 34623±4719 min.mg/dL), but increased in male (26100±1639 vs. 19408±1364 min.mg/dL) ASIC2/βENaC/TrpC6 mice. Liver (0.83±0.05 vs. 1.93±0.34g, p=0.0066) and liver fat (0.011±0.007 vs.0.333±.158, p=0.05) masses, as well as percent liver fat (1.1±0.6 vs. 14.4±4.1%, p=0.006), were reduced in female ASIC2/βENaC/TrpC6 mice after HFD. While liver (1.77±0.13 vs. 2.49±0.15g, p=0.007) and liver fat (0.17±.06 vs. 0.37±.03g, p=0.044) masses were reduced in male ASIC2/βENaC/TrpC6 mice, percent liver fat was not statistically lower (8.8±2.6 vs. 14.7±0.7%, p=0.11). These highly novel findings suggest that ASIC2, βENaC and/or their interaction with TrpC6, protects against HFD induced‐metabolic disease in female, but not male, mice. The mechanisms underlying this response will be examined in future studies. Support or Funding Information This work was support by NIH P01HL051971, P20GM104357, P20GM121334 and R01HL136684. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .