Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice

• Egile Nagusiak: Marija Pinterić (Egilea), Iva I. Podgorski (Egilea), Marijana Popović Hadžija (Egilea), Ivana Tartaro Bujak (Egilea), Ana Dekanić (Egilea), Robert Bagarić (Egilea), Vladimir Farkaš (Egilea), Sandra Sobočanec (Egilea), Tihomir Balog (Egilea)
• Formatua: Liburua
• Argitaratua: MDPI AG, 2020-02-01T00:00:00Z.
• Gaiak: article
• Sarrera elektronikoa: Connect to this object online.

Gaia

Metabolic homeostasis is differently regulated in males and females. Little is known about the mitochondrial Sirtuin 3 (Sirt3) protein in the context of sex-related differences in the development of metabolic dysregulation. To test our hypothesis that the role of Sirt3 in response to a high-fat diet (HFD) is sex-related, we measured metabolic, antioxidative, and mitochondrial parameters in the liver of Sirt3 wild-type (WT) and knockout (KO) mice of both sexes fed with a standard or HFD for ten weeks. We found that the combined effect of Sirt3 and an HFD was evident in more parameters in males (lipid content, glucose uptake, <i>pparγ</i>, <i>cyp2e1</i>, <i>cyp4a14</i>, Nrf2, MnSOD activity) than in females (protein damage and mitochondrial respiration), pointing towards a higher reliance of males on the effect of Sirt3 against HFD-induced metabolic dysregulation. The male-specific effects of an HFD also include reduced Sirt3 expression in WT and alleviated lipid accumulation and reduced glucose uptake in KO mice. In females, with a generally higher expression of genes involved in lipid homeostasis, either the HFD or Sirt3 depletion compromised mitochondrial respiration and increased protein oxidative damage. This work presents new insights into sex-related differences in the various physiological parameters with respect to nutritive excess and Sirt3.

Alearen deskribapena

2076-3921
10.3390/antiox9020174