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. 2017 Dec 13;16(1):243.
doi: 10.1186/s12944-017-0639-7.

Sexual dimorphism in the hepatic protein response to a moderate trans fat diet in senescence-accelerated mice

Steven A Bloomer  1 , Kathryn E Wellen  2   3 , Gregory C Henderson  4
Affiliations

Sexual dimorphism in the hepatic protein response to a moderate trans fat diet in senescence-accelerated mice

Steven A Bloomer et al. Lipids Health Dis. .

Abstract

Background: Aging is characterized by increases in inflammation and oxidative stress, conditions that are exacerbated by environmental factors such as diet. In this study, we investigated the effects of a trans-fatty acid (TFA) diet on the liver in adult (25 wk) and old (60 wk) senescence-accelerated mice (SAMP8 strain) of both sexes. Our goal was to assess the effects of the diet on protein markers of inflammation and oxidative stress in the liver.

Methods: Male and female mice were placed on life-long diets containing similar amounts of total fat (17%), with differing amounts of TFA: 2% (moderate TFA group) or 0.2% of total energy from TFA (control diet group). At the indicated ages, livers were harvested and evaluated for markers of inflammation and oxidative stress, as well as for enzymes of fat metabolism via immunoblotting. Relative densities of protein bands were determined and compared via a three-factor ANOVA.

Results: Compared to males, females demonstrated significantly lower inflammatory protein expression (ICAM-1, MCP-1, COX-2), along with lower expression of the DNA damage marker, Gadd153, and the oxidative stress marker, HO-1. Female mice demonstrated higher expression of antioxidant enzymes (SOD-1, SOD-2, and Ref-1) and lipogenic enzymes (FASN, ACLY) compared to male mice. While HO-1 was elevated in the female mice fed the TFA diet compared to controls, the diet did not affect other markers of oxidative stress or inflammation. However, the diet was associated with significant increases in FASN and ACLY in adult (25 wk) male mice.

Conclusions: Our results suggest sexually dimorphic protein expression in the liver, with female mice demonstrating lower inflammation and increased oxidative stress defenses. Additionally, considering that FASN and ACLY contribute to hepatic lipogenesis, our results suggest a potential mechanism for the dyslipidemia in adult male mice that is associated with TFA diets.

Keywords: ATP citrate lyase; Fatty acid synthase; Inflammation; MCP-1; Oxidative stress.

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Figures

Fig. 1
Fig. 1
Decreased abundance of inflammatory proteins in female mice. Quantitation of ICAM-1 (a), MCP-1 (b), and COX-2 (c) protein abundance in the liver, normalized to the Ponceau stain, and further normalized to the adult, male control group. Top panels: representative immunoblots for target protein expression and Ponceau-stained membranes. Bottom panels: quantitation of target protein expression. Results are expressed as means + S.E.M., n = 5–7 animals per group. † Significant effect of sex within an age or diet group. Brackets designate a significant main effect of sex. * Significant effect of aging within a diet and sex group. AC: adult control diet; AT: adult trans-fat diet; OC: old control diet; OT: old trans-fat diet
Fig. 2
Fig. 2
Female sex increases antioxidant protein expression. Quantitation of Ref-1 (a), γ-GCS (b), SOD-1 (c), and SOD-2 (d) protein abundance in the liver, normalized to the Ponceau stain, and further normalized to the adult, male control group. Top panels: representative immunoblots for target protein expression and Ponceau-stained membranes. Bottom panels: quantitation of target protein expression. Results are expressed as means + S.E.M., n = 5–7 animals per group. † Significant main effect of sex. * Significant effect of aging within a diet and sex group. AC: adult control diet; AT: adult trans-fat diet; OC: old control diet; OT: old trans-fat diet
Fig. 3
Fig. 3
Decreased expression of Gadd153 and HO-1 in female mice. Quantitation of Gadd153 (a), and HO-1 (b) protein abundance in the liver. Top panels: representative immunoblots for target protein expression and Ponceau-stained membranes. Bottom panels: quantitation of target protein expression. Results are expressed as means + S.E.M., n = 5–7 animals per group. † Significant effect of sex within an age or diet group Brackets designate a significant main effect of sex. Ω Significant effect of trans-fat diet within an age and sex group. * Significant effect of age within a sex and diet group. AC: adult control diet; AT: adult trans-fat diet; OC: old control diet; OT: old trans-fat diet
Fig. 4
Fig. 4
Effects of diet, age, and sex on lipogenic enzyme expression. Quantitation of fatty acid synthase (FASN; a) and ATP citrate lyase (ACLY; b) abundance in the liver. Top panels: representative immunoblots for target protein expression and Ponceau-stained membranes. Bottom panels: quantitation of target protein expression. Results are expressed as means + S.E.M., n = 5–7 animals per group. Ω Significant effect of trans-fat diet. † Significant effect of sex. *Significant effect of age within a sex and diet group. AC: adult control diet; AT: adult trans-fat diet; OC: old control diet; OT: old trans-fat diet
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