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hNAG‐1 improves insulin sensitivity and ovarian function in young and aged female mice upon high fat diet treatment
Author(s) -
wang Yujie,
Wu Kaikai,
Guo Dandan,
Guo Chenjie,
Pan Haitao,
Sang Tingting,
Wang Ying,
Wang Xingya
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.lb573
Subject(s) - medicine , endocrinology , biology , leptin , ovary , insulin resistance , insulin , follicular phase , obesity
Nonsteroidal anti‐inflammatory drug‐activated gene‐1 (NAG‐1) is a distant member of the TGF‐β superfamily. Female hNAG‐1 transgenic mice are resistant to high fat diet (HFD)‐induced obesity and have increased lifespan. Progressive gonadal dysfunction has been shown to be an important sign of aging in experimental animals. Whether hNAG‐1 transgenic mice have improved ovarian function has not been studied. We examined the ovarian function in both young (20–28week) and old (50–56 week) female mice upon feeding with high or low fat diets for 16 weeks. We found that ovarian function is improved in hNAG‐1 mice compared to wild type littermates upon both diets, with the most prominent effects observed in older mice. We observed decreased body weight, abdominal fat and lower serum glucose, leptin, insulin and insulin‐like growth factor‐1(IGF‐1) levels, and increased steroid production and increased insulin sensitivity in hNAG‐1 mice compared to wild type mice. These observations were correlated with deregulation of the expression of pro‐inflammatory cytokines and follicular development regulatory genes that suggesting improved ovarian function in hNAG‐1 mice. Histological analysis of the ovaries showed a decrease in the number of primary and secondary follicles in both genotypes upon HFD treatment. However, the ovaries from wild type mice showed an increase in the number of hemorrhagic follicles compared to hNAG‐1 mice, suggesting that hNAG‐1 may improve ovarian function through preserving primordial follicles and increasing oocyte quality. In addition, western blot analysis demonstrated that expression of mTOR/IGF‐1/TLR4 signaling pathways were decreased in young and old hNAG‐1 mice ovaries, and an increase of Foxo/SIRT1 signaling pathway was observed in old hNAG‐1 mice. Taken together, the present results suggested that hNAG‐1 play an important role in improving ovarian function and insulin sensitivity in female Support or Funding Information National Natural Science Foundation of China (Grant No. 81400822). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .