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Chronic high fat diet intake impairs hepatic metabolic parameters in ovariectomized Sirt3 KO mice

Pinterić, Marija; Podgorski, Iva I.; Popović Hadžija, Marijana; Tartaro Bujak, Ivana; Tadijan, Ana; Balog, Tihomir; Sobočanec, Sandra (2021) Chronic high fat diet intake impairs hepatic metabolic parameters in ovariectomized Sirt3 KO mice. International journal of molecular sciences, 22 (8). ISSN 1422-0067

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High fat diet (HFD) is an important factor in the development of metabolic diseases, with liver as metabolic center being highly exposed to its influence. However, the effect of HFD-induced metabolic stress with respect to ovary hormone depletion and sirtuin 3 (Sirt3) is not clear. Here we investigated the effect of Sirt3 in liver of ovariectomized and sham female mice upon 10 weeks of feeding with standard-fat diet (SFD) or HFD. Liver was examined by Folch, gas chromatography and lipid hydroperoxide analysis, histology and oil red staining, RT-PCR, Western blot, antioxidative enzyme and oxygen consumption analyses. In SFD-fed WT mice, ovariectomy increased Sirt3 and fatty acids synthesis, maintained mitochondrial function, and decreased levels of lipid hydroperoxides. Combination of ovariectomy and Sirt3 depletion reduced pparα, Scd-1 ratio, MUFA proportions, CII-driven respiration, and increased lipid damage. HFD compromised CII-driven respiration and activated peroxisomal ROS scavenging enzyme catalase in sham mice, whereas in combination with ovariectomy and Sirt3 depletion, increased body weight gain, expression of NAFLD- and oxidative stress-inducing genes, and impaired response of antioxidative system. Overall, this study provides evidence that protection against harmful effects of HFD in female mice is attributed to the combined effect of female sex hormones and Sirt3, thus contributing to preclinical research on possible sex-related therapeutic agents for metabolic syndrome and associated diseases.

Item Type: Article
Uncontrolled Keywords: sirtuin 3 ; ovariectomy ; high fat diet ; fatty liver
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Division of Materials Chemistry
Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Sirtuin3 kao posrednik mitohondrijske funkcije u estrogen-ovisnoj otpornosti na oksidativni stres i prehranu s visokim udjelom mastiBalog, TihomirIP-2014-09-4533HRZZ
Depositing User: Sandra Sobočanec
Date Deposited: 25 Jan 2022 13:28
DOI: 10.3390/ijms22084277

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