Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver
© 2017 the American Physiological Society. The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potenti...
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th-mahidol.417782019-03-14T15:02:46Z Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver Natsasi Chukijrungroat Tanaporn Khamphaya Jittima Weerachayaphorn Thaweesak Songserm Vitoon Saengsirisuwan Mahidol University Kasetsart University Biochemistry, Genetics and Molecular Biology © 2017 the American Physiological Society. The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFDfed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFDinduced hepatic steatosis. 2018-12-21T06:44:26Z 2019-03-14T08:02:46Z 2018-12-21T06:44:26Z 2019-03-14T08:02:46Z 2017-08-02 Article American Journal of Physiology - Endocrinology and Metabolism. Vol.313, No.2 (2017), E203-E212 10.1152/ajpendo.00076.2017 15221555 01931849 2-s2.0-85027019130 https://repository.li.mahidol.ac.th/handle/123456789/41778 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85027019130&origin=inward |
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Biochemistry, Genetics and Molecular Biology Natsasi Chukijrungroat Tanaporn Khamphaya Jittima Weerachayaphorn Thaweesak Songserm Vitoon Saengsirisuwan Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver |
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© 2017 the American Physiological Society. The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFDfed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFDinduced hepatic steatosis. |
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Mahidol University |
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Mahidol University Natsasi Chukijrungroat Tanaporn Khamphaya Jittima Weerachayaphorn Thaweesak Songserm Vitoon Saengsirisuwan |
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Article |
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Natsasi Chukijrungroat Tanaporn Khamphaya Jittima Weerachayaphorn Thaweesak Songserm Vitoon Saengsirisuwan |
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Natsasi Chukijrungroat |
title |
Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver |
title_short |
Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver |
title_full |
Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver |
title_fullStr |
Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver |
title_full_unstemmed |
Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver |
title_sort |
hepatic fgf21 mediates sex differences in high-fat high-fructose diet-induced fatty liver |
publishDate |
2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/41778 |
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1763494913898446848 |