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

Pinterić, Marija; Podgorski, Iva I.; Hadžija, Mirko; Bujak, Ivana Tartaro; Dekanić, Ana; Bagarić, Robert; Farkaš, Vladimı́r; Sobočanec, Sandra; Balog, Tihomir

doi:10.3390/antiox9020174

Cited by 12 publications

(17 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fasting glucose level remained unchanged by either ovx or Sirt3 depletion in both SFD and HFD-fed mice ( Figure 2 A). In agreement with our previous observations [ 13 ], we found no change in body weight in SFD- and HFD-fed sham mice (data not shown). However, body weight gain was affected differently in ovx KO mice, depending on type of diet: SFD-fed KO ovx mice gained less weight than WT ovx ( a p < 0.05) or sham KO mice (** p < 0.01) ( Figure 2 B).…”

Section: Resultssupporting

confidence: 94%

“…It promotes mitochondrial oxidative metabolism via deacetylation of numerous metabolic enzymes, including those involved in FA catabolism, as demonstrated earlier by an abnormal accumulation of FA oxidation intermediates in Sirt3 KO mice [ 4 ]. It was also shown that Sirt3 expression is reduced during chronic HFD in male mice [ 4 , 13 ]. Although E2-dependent protection includes improvement of mitochondrial function [ 14 ], it is not clear whether Sirt3, as a pivotal factor regulating mitochondrial biogenesis and reactive oxygen species (ROS) management, participates in these events.…”

Section: Introductionmentioning

confidence: 99%

“…In our recent study, we found significant sex differences in mice at the level of metabolic, oxidant, antioxidant, and mitochondrial parameters upon HFD. Also, we pointed towards a different role of Sirt3 in males and females under the conditions of nutritive stress, with higher reliance of males than females to the effect of Sirt3 against HFD-induced metabolic dysregulation [ 13 ]. These observations led us to the hypothesis that females’ protection from HFD-induced metabolic dysregulation in vivo could be attributed to the complementary beneficial effect of Sirt3 and ovary hormones.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Pinterić

Podgorski

Hadžija

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Pinterić

Podgorski

Hadžija

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, SIRT3 deficiency resulted in triglyceride accumulation in the liver. However, an HFD reduces only SIRT3 levels in males [ 361 ]. Contrarily, modulation of the SIRT3/FOXO1 pathway through salvianolic acid B was shown to improve NAFLD in rats, by reducing oxidative stress [ 362 ].…”

Section: The Role Of Sirtuins In Metabolic Tissuesmentioning

confidence: 99%

Sirtuins-Mediated System-Level Regulation of Mammalian Tissues at the Interface between Metabolism and Cell Cycle: A Systematic Review

Maissan

Mooij

Barberis

2021

Biology

View full text Add to dashboard Cite

Sirtuins are a family of highly conserved NAD+-dependent proteins and this dependency links Sirtuins directly to metabolism. Sirtuins’ activity has been shown to extend the lifespan of several organisms and mainly through the post-translational modification of their many target proteins, with deacetylation being the most common modification. The seven mammalian Sirtuins, SIRT1 through SIRT7, have been implicated in regulating physiological responses to metabolism and stress by acting as nutrient sensors, linking environmental and nutrient signals to mammalian metabolic homeostasis. Furthermore, mammalian Sirtuins have been implicated in playing major roles in mammalian pathophysiological conditions such as inflammation, obesity and cancer. Mammalian Sirtuins are expressed heterogeneously among different organs and tissues, and the same holds true for their substrates. Thus, the function of mammalian Sirtuins together with their substrates is expected to vary among tissues. Any therapy depending on Sirtuins could therefore have different local as well as systemic effects. Here, an introduction to processes relevant for the actions of Sirtuins, such as metabolism and cell cycle, will be followed by reasoning on the system-level function of Sirtuins and their substrates in different mammalian tissues. Their involvement in the healthy metabolism and metabolic disorders will be reviewed and critically discussed.

show abstract

“…In most mammals, females show lower incidence of some age-related pathologies linked with oxidative stress conditions, and this sex difference disappears after menopause, which led to the conclusion that this protection is attributed to the effect of sex hormones [ 28 ]. By conducting in vivo experiments on Sirt3 wild-type (WT) and knockout (KO) mice of both sexes fed with a standard or high-fat diet (HFD) for ten weeks, Pinterić et al [ 29 ] found significant sex differences in male and female mice responses at the metabolic level, oxidant/antioxidant status, and liver mitochondrial parameters. Their study points towards a different role of SIRT3 in males and females under the conditions of nutritive stress.…”

mentioning

confidence: 99%