Short-term inhibition of SREBP-1c expression reverses diet-induced non-alcoholic fatty liver disease in mice

Frederico, Marisa Jádna Silva; Vitto, Marcelo F.; Cesconetto, Patrícia Acordi; Engelmann, Julia; Souza, Daniela R.; Luz, Gabrielle da; Pinho, Ricardo A.; Ropelle, Eduardo Rochete; Cintra, Dennys Esper; Souza, Cláudio Teodoro de

doi:10.3109/00365521.2011.613945

Cited by 38 publications

(28 citation statements)

References 36 publications

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“…In this respect, exceed lipid in the body due to HFD could directly or indirectly promotes fat accumulation in the liver. Evidence showing that the increase of lipogenic factors and decrease of lipolytic factors induced fat accumulation in the liver was well known, through both human [19, 20] and animal studies [21, 22]. In this study, as expected, chronic HFD increased lipogenic factor, such as FAS with decreased lipolytic factors, such as AMPK and CPT1, which induced increased fat accumulation, size, and liver weight.…”

Section: Discussionsupporting

confidence: 71%

Exercise without dietary changes alleviates nonalcoholic fatty liver disease without weight loss benefits

Bae

2018

Lipids Health Dis

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BackgroundThis study aimed to analyze the effect of exercise and/or dietary change on improvement of non-alcoholic fatty liver disease (NAFLD) in chronic high-fat diet (HFD)-induced obese mice.MethodsForty male C57BL/6 (8 weeks old) mice were divided into normal diet (CO, n = 8) and high-fat diet (HF, n = 32) groups. The HF group was fed with 60% fat chow for 16 weeks to induce obesity. After the obesity induction period, the HF group was subdivided into HFD + sedentary (n = 8), HFD + training (HFT, n = 8), dietary change to normal-diet + sedentary (HFND, n = 8), and dietary change to normal-diet + training (HFNDT, n = 8) groups, and the mice in the training groups underwent treadmill training for 8 weeks, 5 times per week, 40 min per day.ResultsA 24-week HFD induced increase of cannabinoid-1 receptor (CB1), fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK) protein expressions (p < 0.05) and decrease of p-AMPK and carnitine palmitoyltransferase1 (CPT1) protein expressions (P < 0.05), resulting in increased liver fat accumulation. Treatment of exercise with dietary change and dietary change alone decreased CB1 and AMPK protein expressions with increased p-AMPK and CPT1 protein expressions (P < 0.05), leading to decreased body weight and liver fat (P < 0.05). The CB1 and FAS protein expressions in the HFT group were still higher than those in the CO group (P < 0.05), but the p-AMPK and CPT1 protein expressions were higher than those in the HF group (P < 0.05). Moreover, improved glucose tolerance and decreased liver fat were confirmed, although treatment of exercise alone had no effect on weight loss compared to pre-exercise.ConclusionsEven in the case of obesity induced by chronic HFD, exercise and/or dietary interventions have preventive and therapeutic effects on fat accumulation in the liver, resulting from upregulations of lipolytic factors. Therefore, the results of this study suggested that treatment of exercise alone without dietary change also leads to improvement of NAFLD and glucose tolerance without weight loss benefits.

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Section: Discussionsupporting

confidence: 71%

Exercise without dietary changes alleviates nonalcoholic fatty liver disease without weight loss benefits

Bae

2018

Lipids Health Dis

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“…The importance of the SREBP-1c in fat metabolism in liver has been studied. To better clarify its role, some techniques were performed to achieve direct or indirect inhibition or up-regulation of SREBP-1c, such as liver-specific SREBP-1 knockout mice (Yahagi et al, 2002), mice germline knockouted for SREBP-1a and 1c (Shimano et al, 1997) and SREBP-1c (Liang et al, 2002), adenovirus-mediated overexpression or recent study performed by our group (Frederico et al, 2011). In an elegant study, Knebel and colleagues generated mice with liver-specific over-expression of mature human SREBP-1c under control of the albumin promoter and a liver-specific enhancer (alb-SREBP-1c) to analyze systemic perturbations caused by this distinct alteration.…”

Section: Groups (N = 8)mentioning

confidence: 99%

RETRACTED: Reversion of hepatic steatosis by exercise training in obese mice: The role of sterol regulatory element-binding protein-1c

et al. 2012

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“…In that model, increased hypertension led to elevated liver triglycerides and adiponectin but phosphorylation of AMPKα and ACC were decreased [36]. Feeding mice a high fat diet alone is known to reduce adiponectin and AMPK phosphorylation [37; 38]. In our model, HF+E did not result in an increase in adiponectin but there is an increase in AMPKα phosphorylation.…”

Section: Discussionmentioning

confidence: 70%

Increased dietary fat contributes to dysregulation of the LKB1/AMPK pathway and increased damage in a mouse model of early-stage ethanol-mediated steatosis

Shearn

Smathers

Jiang

et al. 2013

The Journal of Nutritional Biochemistry

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Objective To examine the interaction of moderate and high dietary fat and ethanol with respect to formation of steatosis and regulation of the AMP-activated protein kinase (AMPK) pathway in a mouse model of chronic ethanol consumption. Methods Male C57BL/6J mice were pair-fed a modified Lieber-DeCarli diet composed of either moderate fat (30% fat-derived calories (MF)) or high fat (45% fat-derived calories (HF)) combined with increasing concentrations of ethanol (2–6%) for 6-weeks. Results Chronic ethanol consumption resulted in significant increases in plasma alanine aminotransferase in MF (1.84-fold) and HF mice (2.33-fold), yet liver triglycerides only increased significantly in the HF model (1.62-fold). Ethanol addition significantly increased plasma adiponectin under conditions of MF but not HF. In combination with MF, the addition of ethanol significantly decreased total and hepatic pThr172AMPKα and acetyl CoA Carboxylase (ACC). HF plus ethanol decreased pSer108AMPKβ yet a marked 1.5-fold increase in pThr172AMPKα occurred. No change was evident in pSer79ACC under conditions of ethanol and HF ingestion. In both models, nuclear levels of SREBP1c, ChREBP were decreased. Surprisingly, MF plus ethanol significantly elevated protein expression of MCAD, LCAD and VLCAD but did not significantly affect mRNA expression of other proteins involved in β-oxidation and fatty acid synthesis. HF plus ethanol significantly reduced mRNA expression of both SCD-1 and ELOVL5, but did not have an effect on MCAD or LCAD. Conclusion These data suggest that when co-ingested with ethanol, dietary fat differentially contributes to dysregulation of adiponectin-dependent activation of the AMPK pathway in the liver of mice.

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Short-term inhibition of SREBP-1c expression reverses diet-induced non-alcoholic fatty liver disease in mice

Abstract: Our results demonstrate that the inhibition of SREBP-1c decreased the expression of lipogenic enzymes, reducing the accumulation of triglycerides and, finally, reversing hepatic steatosis in mice.

Cited by 38 publications

References 36 publications

Exercise without dietary changes alleviates nonalcoholic fatty liver disease without weight loss benefits

Exercise without dietary changes alleviates nonalcoholic fatty liver disease without weight loss benefits

RETRACTED: Reversion of hepatic steatosis by exercise training in obese mice: The role of sterol regulatory element-binding protein-1c

Increased dietary fat contributes to dysregulation of the LKB1/AMPK pathway and increased damage in a mouse model of early-stage ethanol-mediated steatosis

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