Beta-Cell Injury in Ncb5or-null Mice is Exacerbated by Consumption of a High-Fat Diet.

European Journal of Lipid Science and Technology : EJLST
Ying GuoHao Zhu

Abstract

NADH-cytochrome b5 oxidoreductase (Ncb5or) in endoplasmic reticulum (ER) is involved in fatty acid metabolism, and Ncb5or(-/-) mice fed standard chow (SC) are insulin-sensitive but weigh less than wild type (WT) littermates. Ncb5or(-/-) mice develop hyperglycemia at about age 7 weeks due to β-cell dysfunction and loss associated with saturated fatty acid accumulation and manifestations of ER and oxidative stress. Here we report that when Ncb5or(-/-) mice born to heterozygous mothers fed a high fat (HF) diet continue to ingest HF, they weigh as much as SC-fed WT at age 5 weeks. By age 7 weeks, diabetes mellitus develops in all HF-fed vs. 68% of SC-fed Ncb5or(-/-) mice. Islet β-cell content in age 5-week Ncb5or(-/-) mice fed HF for 7 days is lower (53%) than for those fed SC (63%), and both are lower than for WT (75%, SC, vs. 69%, HF). Islet transcript levels for markers of mitochondrial biogenesis (PGC-1α) and ER stress (ATF6α) are higher in Ncb5or(-/-) than WT mice but not significantly affected by diet. Consuming a HF diet exacerbates Ncb5or(-/-) β-cell accumulation of intracellular saturated fatty acids and increases the frequency of ER distention from 11% (SC) to 47% (HF), thus accelerates β-cell injury in Ncb5or(-/-) mice.

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Citations

Apr 21, 2016·The Journal of Endocrinology·Haijiang WuHuijun Duan
Mar 22, 2014·The Journal of Biological Chemistry·Haowei SongJohn Turk
Oct 8, 2020·Cells·Joseph M Chambers, Rebecca A Wingert

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