Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia
Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on...
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doaj-84aa0be4704240099febee56001343102021-04-26T23:04:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01224527452710.3390/ijms22094527Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum DyslipidemiaHana Malinská0Martina Hüttl1Denisa Miklánková2Jaroslava Trnovská3Iveta Zapletalová4Martin Poruba5Irena Marková6Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicDepartment of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech RepublicDepartment of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicOvarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (<i>p </i>˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (<i>p </i>˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (<i>p </i>˂ 0.05) and decreased CYP4A (<i>p </i>˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (<i>p </i>˂ 0.01), lipogenesis (<i>p </i>˂ 0.05) and lipolysis (<i>p </i>˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal periodhttps://www.mdpi.com/1422-0067/22/9/4527ovariectomymetabolic syndromebrown adipose tissuehepatic steatosisobesityinsulin resistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hana Malinská Martina Hüttl Denisa Miklánková Jaroslava Trnovská Iveta Zapletalová Martin Poruba Irena Marková |
spellingShingle |
Hana Malinská Martina Hüttl Denisa Miklánková Jaroslava Trnovská Iveta Zapletalová Martin Poruba Irena Marková Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia International Journal of Molecular Sciences ovariectomy metabolic syndrome brown adipose tissue hepatic steatosis obesity insulin resistance |
author_facet |
Hana Malinská Martina Hüttl Denisa Miklánková Jaroslava Trnovská Iveta Zapletalová Martin Poruba Irena Marková |
author_sort |
Hana Malinská |
title |
Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia |
title_short |
Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia |
title_full |
Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia |
title_fullStr |
Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia |
title_full_unstemmed |
Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia |
title_sort |
ovariectomy-induced hepatic lipid and cytochrome p450 dysmetabolism precedes serum dyslipidemia |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-04-01 |
description |
Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (<i>p </i>˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (<i>p </i>˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (<i>p </i>˂ 0.05) and decreased CYP4A (<i>p </i>˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (<i>p </i>˂ 0.01), lipogenesis (<i>p </i>˂ 0.05) and lipolysis (<i>p </i>˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal period |
topic |
ovariectomy metabolic syndrome brown adipose tissue hepatic steatosis obesity insulin resistance |
url |
https://www.mdpi.com/1422-0067/22/9/4527 |
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