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Article

Chronic High Fat Diet Intake Impairs Hepatic Metabolic Parameters in Ovariectomized Sirt3 KO Mice

1
Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia
2
Division of Materials Chemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Equal contribution.
Academic Editor: Muriel Le Romancer
Int. J. Mol. Sci. 2021, 22(8), 4277; https://doi.org/10.3390/ijms22084277
Received: 25 March 2021 / Revised: 14 April 2021 / Accepted: 16 April 2021 / Published: 20 April 2021
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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. View Full-Text
Keywords: sirtuin 3; ovariectomy; high fat diet; fatty liver sirtuin 3; ovariectomy; high fat diet; fatty liver
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MDPI and ACS Style

Pinterić, M.; Podgorski, I.I.; Popović Hadžija, M.; Tartaro Bujak, I.; Tadijan, A.; Balog, T.; Sobočanec, S. Chronic High Fat Diet Intake Impairs Hepatic Metabolic Parameters in Ovariectomized Sirt3 KO Mice. Int. J. Mol. Sci. 2021, 22, 4277. https://doi.org/10.3390/ijms22084277

AMA Style

Pinterić M, Podgorski II, Popović Hadžija M, Tartaro Bujak I, Tadijan A, Balog T, Sobočanec S. Chronic High Fat Diet Intake Impairs Hepatic Metabolic Parameters in Ovariectomized Sirt3 KO Mice. International Journal of Molecular Sciences. 2021; 22(8):4277. https://doi.org/10.3390/ijms22084277

Chicago/Turabian Style

Pinterić, Marija, Iva I. Podgorski, Marijana Popović Hadžija, Ivana Tartaro Bujak, Ana Tadijan, Tihomir Balog, and Sandra Sobočanec. 2021. "Chronic High Fat Diet Intake Impairs Hepatic Metabolic Parameters in Ovariectomized Sirt3 KO Mice" International Journal of Molecular Sciences 22, no. 8: 4277. https://doi.org/10.3390/ijms22084277

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