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Hyperandrogenism an...
Hyperandrogenism and insulin resistance contribute to hepatic steatosis and inflammation in female rat liver.
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- Zhang, Yuehui (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Meng, Fanci (author)
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Sun, Xiaoyan (author)
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Sun, Xue (author)
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- Hu, Min (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Cui, Peng (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Vestin, Edvin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Li, Xin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Li, Wei (author)
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Wu, Xiao-Ke (author)
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- Jansson, John-Olov, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Shao, Linus Ruijin, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Billig, Håkan, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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(creator_code:org_t)
- 2018-02-09
- 2018
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:26, s. 18180-18197
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http://www.oncotarge...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Women with polycystic ovary syndrome (PCOS) are at high risk for nonalcoholic fatty liver disease (NAFLD). While insulin resistance is a common trait for both PCOS and NAFLD, hyperandrogenism is also considered to be a key factor contributing to PCOS, and the molecular mechanisms behind the interactions between insulin resistance and hyperandrogenism in the female liver remain largely unexplored. Using chronic treatment with insulin and/or human chorionic gonadotropin (hCG), we showed that all female rats with different treatments induced imbalance between de novo lipogenesis and mitochondrial β-oxidation via the Pparα/β-Srebp1/2-Acc1 axis, resulting in varying degrees of hepatic steatosis. Given the fact that hepatic lipid metabolism and inflammation are tightly linked processes, we found that hCG-induced hyperandrogenic rats had strongly aggravated hepatic inflammation. Further mechanistic investigations revealed that dysregulation of the IRS-PI3K-Akt signaling axis that integrated aberrant inflammatory, apoptotic and autophagic responses in the liver was strongly associated with hyperandrogenism itself or combined with insulin resistance. Additionally, we found that hCG-treated and insulin+hCG-induced rats developed visceral adipose tissue inflammation characterized by the presence of "crown like" structure and increased inflammatory gene expression. Because a more pronounced hepatic steatosis, inflammatory responses, and hepatocyte cell damage were observed in insulin+hCG-induced PCOS-like rats, our finding suggest that NAFLD seen in PCOS patients is dependent of hyperandrogenism and insulin resistance.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- By the author/editor
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Zhang, Yuehui
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Meng, Fanci
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Sun, Xiaoyan
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Sun, Xue
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Hu, Min
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Cui, Peng
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Vestin, Edvin
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Li, Xin
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Li, Wei
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Wu, Xiao-Ke
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Jansson, John-Ol ...
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Shao, Linus Ruij ...
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Billig, Håkan, 1 ...
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Oncotarget
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University of Gothenburg