title: Effect of high-fat diet-induced obesity on the Akt/FoxO/Smad signaling pathway and the follicular development of the mouse ovary.
abstract: Obesity has a negative effect on ovarian functions, which is reported to increase the risk of infertility. The mechanism underlying obesity‑induced infertility is not yet clear. The present study established a high‑fat diet (HFD)‑induced obesity mouse model to elucidate the mechanisms underlying the effect of HFD‑induced obesity on follicular development in the mouse ovary. The 4‑week‑old female mice were fed with HFD or normal control (NC) diet for 15 or 20 weeks. Body mass index was used to demonstrate that the mice were obese following HFD treatment. The follicular development of the ovaries from the HFD group mice was retarded in a time‑dependent manner, as demonstrated by morphological and histological examination of the ovaries. Further investigation via western blot analysis demonstrated that the activity of the transcription factor, forkhead box O3a (FoxO3a), was increased by HFD through downregulated FoxO3a phosphorylation, which may contribute to the inhibited development of ovarian follicles. To determine the regulatory mechanism of FoxO3 on the follicular development, the expression levels of FoxO3a target protein, Smad1/5/8, were also determined and there was significant decrease in phosphorylated Smad1/5/8 in the ovaries from the HFD group compared with the NC group, indicating that FoxO3a/Smad1/5/8 may be important in the regulation of follicular development. The expression levels of the upstream regulator of FoxO3a, Akt, were also examined and it was demonstrated that Akt phosphorylation was significantly reduced in the HFD group compared with the NC group, indicating that Akt/FoxO3a may be also involved in follicular development. Together, the experiments demonstrated that HFD‑induced obesity affected the activity of the Akt/FoxO3a/Smad1/5/8 signaling pathway in a time‑dependent manner during the follicular development of the mouse ovary, leading to abnormal follicular development. These findings may provide part of a theoretical basis for the clinical prevention and treatment of obesity-associated female infertility.
authors: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350007, P.R. China.
authors: Yanqing
authors: Y
authors: Wu
authors: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350007, P.R. China.
authors: Zhenghong
authors: Z
authors: Zhang
authors: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350007, P.R. China.
authors: Xinghui
authors: X
authors: Liao
authors: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350007, P.R. China.
authors: Lingbin
authors: L
authors: Qi
authors: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350007, P.R. China.
authors: Yiping
authors: Y
authors: Liu
authors: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350007, P.R. China.
authors: Zhengchao
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*
chemical_list: D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D051785:Smad Proteins; D051057:Proto-Oncogene Proteins c-akt