Short-term strength training reduces gluconeogenesis and NAFLD in obese mice

in Journal of Endocrinology
Correspondence should be addressed to L P de Moura: leandropereiram@hotmail.com
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Non-alcoholic fatty liver disease (NAFLD) has a positive correlation with obesity, insulin resistance and type 2 diabetes mellitus (T2D). The aerobic training is an important tool in combating NAFLD. However, no studies have demonstrated the molecular effects of short-term strength training on the accumulation of hepatic fat in obese mice. This study aimed to investigate the effects of short-term strength training on the mechanisms of oxidation and lipid synthesis in the liver of obese mice. The short duration protocol was used to avoid changing the amount of adipose tissue. Swiss mice were separated into three groups: lean control (CTL), sedentary obese (OB) and strength training obese (STO). The obese groups were fed a high-fat diet (HFD) and the STO group performed the strength training protocol 1 session/day for 15 days. The short-term strength training reduced hepatic fat accumulation, increasing hepatic insulin sensitivity and controlling hepatic glucose production. The obese animals increased the mRNA of lipogenic genes Fasn and Scd1 and reduced the oxidative genes Cpt1a and Ppara. On the other hand, the STO group presented the opposite results. Finally, the obese animals presented higher levels of lipogenic proteins (ACC and FAS) and proinflammatory cytokines (TNF-α and IL-1β), but the short-term strength training was efficient in reducing this condition, regardless of body weight loss. In conclusion, there was a reduction of obesity-related hepatic lipogenesis and inflammation after short-term strength training, independent of weight loss, leading to improvements in hepatic insulin sensitivity and glycemic homeostasis in obese mice. Key points: (1) Short-term strength training (STST) reduced fat accumulation and inflammation in the liver; (2) Hepatic insulin sensitivity and HPG control were increased with STST; (3) The content and activity of ACC and content of FAS were reduced with STST; (4) STST improved hepatic fat accumulation and glycemic homeostasis; (5) STST effects were observed independently of body weight change.

Downloadable materials

  • Figure 1: Description of how the experimental design was elaborated
  • supplementary Figure 2
  • supplementary Figure 3
  • supplementary Figure 4
  • supplementary Figure 5
  • Supplementary Table 1. List of hepatic genes and proteome whose expression covaries with basal glucose in plasma of BXD mice fed with HFD

 

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    Experimental design. Summarized representation of the experiments during the short-term strength training protocol. The tests were performed 8 h after the exercise session respecting a period of 8-h fasting. MVCC, maximum voluntary carrying capacity.

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    Physiological parameters of CTL, OB and STO groups. (A and B) Body mass of the animals at the beginning and at the end of the experiment. (C and D) Fasting glucose and insulinemia (after 8 h of fasting), respectively. (E and F) Adipose tissue weight of the epididymal and retroperitoneal regions, respectively. *P < 0.05 vs CTL; # P < 0.05 vs OB (n = 4–6 per group). We used Kruskal–Wallis test followed by Dunn’s multiple comparisons tests in (B) and (D) and one-way ANOVA followed by Bonferroni’s post hoc test in A, C, E and F.

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    The hepatic fat content of CTL, OB and STO groups. (A) Hematoxylin and eosin staining and oil red O staining of the right lobe from three experimental groups. (B) TG content normalized for liver weight. (C) Liver lipid droplet area of the three groups, from oil red O staining. (D) Oil red O stained area of the three groups. *P < 0.05 vs CTL; # P < 0.05 vs OB (n = 5–6 per group). In (B), we used one-way ANOVA followed by Bonferroni’s post hoc test. In (C) we used Mann–Whitney test between OB and STO groups. In (D) we used Student’s t-test between OB and STO groups.

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    Hepatic glucose production during ipPTT and hepatic insulin sensitivity. (A) Glycemic curve during ipPTT. (B) The area under the curve during ipPTT. (C) Bands of p-Aktser473 levels in the liver after insulin stimulus. (D) Quantification of hepatic p-Akt/Akt of CTL and OB groups. (E) Quantification of hepatic p-Akt of OB and STO groups. Only the bands of the animals stimulated with insulin were quantified. (F and G) Interaction network and correlation plots showing correlations between basal glucose levels (fasted state), hepatic mRNAs (shown in green) and proteins (shown in purple) of BXD mice fed with high-fat diet. Positive and negative Pearson’s correlation coefficients are indicated by red and blue lines, respectively. Correlation plots of each analysis are also displayed, with Pearson’s r and P-values indicated. In (A): a P < 0.05 for CT vs OB; b P < 0.05 for CT vs STO; c P < 0.05 for OB vs STO. In (B, D and E): *P < 0.05 vs CT; # P < 0.05 vs OB (n = 7 per group in A and B; n = 6 per group in D and E). In (A), we used two-way ANOVA test with Bonferroni’s correction for multiple comparisons. In (B), we used Kruskal–Wallis test followed by Dunn’s multiple comparisons tests. In (D and E), we used Student’s t-test.

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    Parameters of hepatic lipogenesis, fat oxidation, and inflammation profile. (A) Levels of mRNA genes related to lipogenesis (Fasn and Scd1) and oxidation (Cpt1a and Ppara) of CTL and OB groups. (B) Bands of the lipogenic proteins in the liver of mice from CTL and OB groups after insulin stimulus. (C) Quantification of hepatic p-ACCser79/ACC of CTL and OB groups. (D and E) Quantification of hepatic ACC and FAS content, respectively, of CTL and OB groups. (F) Bands of the proinflammatory proteins in the liver of mice from CTL and OB groups after insulin stimulus. (G and H) Quantification of hepatic TNF-α and IL-1β content, respectively, of CTL and OB groups. (I) Levels of mRNA genes related to lipogenesis (Fasn and Scd1) and oxidation (Cpt1a and Ppara) of OB and STO groups. (J) Bands of the lipogenic proteins in the liver of mice from OB and STO groups after insulin stimulus. (K) Quantification of hepatic p-ACCser79/ACC of OB and STO groups. (L and M) Quantification of hepatic ACC and FAS content, respectively, of OB and STO groups. (N) Bands of the proinflammatory proteins in the liver of mice from OB and STO groups after insulin stimulus. (O and P) Quantification of hepatic TNF-α and IL-1β content, respectively, of OB and STO groups. Only the bands of the animals stimulated with insulin were quantified. *P < 0.05 vs CT; # P < 0.05 vs OB (n = 5-6 per group). In (A) (Fasn) and I (Fasn) we used Welch’s t test. In (A) (Cpt1a), (C, D, E, H and I) (Scd1 and Cpt1a), (K, L, O and P) we used Student’s t-test. In the others, we used Mann–Whitney test.

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    Role of short-term strength training on lipid metabolism in the liver, independent of body weight change. Obesity provides insulin resistance, fasting hyperglycemia and increase of lipid synthesis mechanisms in the liver, increasing inflammation and protein level of ACC and FAS, Fasn and Scd1 transcription, and ACC activity. At the same time, this condition reduces the transcription of oxidative genes Ppara and Cpt1a. On the other hand, short-term strength training provided the opposite effects even without a reduction in body adiposity. Therefore, we demonstrated for the first time that the present short exercise protocol could be an important tool in the combat and/or treatment of NAFLD. A full colour version of this figure is available at https://doi.org/10.1530/JOE-18-0567.

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