Fructose supplementation impairs rat liver autophagy through mTORC activation without inducing endoplasmic reticulum stress

Baena, Miguel; Sangüesa, Gemma; Hutter, Natalia; Sánchez, Rosa María Galán; Roglans, Núria; Laguna, Juan C.; Alegret, Marta

doi:10.1016/j.bbalip.2014.11.003

Cited by 48 publications

(62 citation statements)

References 38 publications

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“…Significant past research has implicated dysfunction in autophagy machinery, and autophagosome formation and clearance as a contributing factor in NAFLD (Mei et al 2011; D r a f t González-Rodríguez et al 2014;Kwanten et al 2014;Baena et al 2015). We note significant repressions in total LC3 and BNIP3 contents along with suggestions of lowered mRNA of Beclin, Atg7 and Bnip3 mRNAs in WD fed animals, suggesting a repression in some aspects of autophagy machinery at this stage.…”

Section: Discussionmentioning

confidence: 52%

“…al (Glick et al 2012) demonstrated that knockout of BNIP3, a gene imperative for mitophagy, in young mice resulted in liver steatosis compared to their wild type littermates under normal feeding conditions, indicating the importance of mitophagy in hepatic health. However, the impacts of lipid-induced toxicity on hepatic autophagy have not been fully elucidated, as both increases and decreases in autophagy have been noted following lipid overload (Cai et al 2014;Baena et al 2015). Lira et al (2013) have demonstrated in muscle that exercise training enhances basal autophagy, including mitophagy, which appears necessary for training-induced adaptations.…”

Section: Introductionmentioning

confidence: 99%

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Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice

Rosa‐Caldwell

Lee

Brown

et al. 2017

Appl. Physiol. Nutr. Metab.

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Obesity is a known risk factor for the development of hepatic disease; obesity-induced fatty liver can lead to inflammation, steatosis, and cirrhosis and is associated with degeneration of the mitochondria. Lifestyle interventions such as physical activity may ameliorate this condition. The purpose of this study was to investigate regulation of mitochondrial and autophagy quality control in liver following Western diet-induced obesity and voluntary physical activity. Eight-week-old C57BL/6J mice were fed a Western diet (WD) or normal chow (NC, control) for 4 weeks; afterwards, groups were divided into voluntary wheel running (VWR) or sedentary (SED) conditions for an additional 4 weeks. WD-SED animals had a median histology score of 2, whereas WD-VWR was not different from NC groups (median score 1). There was no difference in mRNA of inflammatory markers Il6 and Tnfa in WD animals. WD animals had 50% lower mitochondrial content (COX IV and Cytochrome C proteins), 50% lower Pgc1a mRNA content, and reduced content of mitochondrial fusion and fission markers. Markers of autophagy were increased in VWR animals, regardless of obesity, as measured by 50% greater LC3-II/I ratio and 40% lower p62 protein content. BNIP3 protein content was 30% less in WD animals compared with NC animals, regardless of physical activity. Diet-induced obesity results in derangements in mitochondrial quality control that appear to occur prior to the onset of hepatic inflammation. Moderate physical activity appears to enhance basal autophagy in the liver; increased autophagy may provide protection from hepatic fat accumulation.

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Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice

Rosa‐Caldwell

Lee

Brown

et al. 2017

Appl. Physiol. Nutr. Metab.

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“…Our research group has shown that liquid fructose supplementation in female rats fed a standard chow diet (two weeks to two months) induces glucose intolerance and IR [12,13,14,15]. However, unhealthy human dietary patterns frequently include not only excessive added sugars, but also excessive fat intake, particularly saturated fats [16].…”

Section: Introductionmentioning

confidence: 99%

The Addition of Liquid Fructose to a Western-Type Diet in LDL-R−/− Mice Induces Liver Inflammation and Fibrogenesis Markers without Disrupting Insulin Receptor Signalling after an Insulin Challenge

et al. 2017

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A high consumption of fat and simple sugars, especially fructose, has been related to the development of insulin resistance, but the mechanisms involved in the effects of these nutrients are not fully understood. This study investigates the effects of a Western-type diet and liquid fructose supplementation, alone and combined, on insulin signalling and inflammation in low-density lipoprotein (LDL) receptor-deficient mice (LDL-R−/−). LDL-R−/− mice were fed chow or Western diet ±15% fructose solution for 12 weeks. Plasma glucose and insulin, and the expression of genes related to inflammation in the liver and visceral white adipose tissue (vWAT), were analysed. V-akt murine thymoma viral oncogene homolog-2 (Akt) activation was measured in the liver of the mice after a single injection of saline or insulin. None of the dietary interventions caused inflammation in vWAT, whereas the Western diet induced hepatic inflammation, which was further enhanced by liquid fructose, leading also to a significant increase in fibrogenesis markers. However, there was no change in plasma glucose or insulin, or insulin-induced Akt phosphorylation. In conclusion, hepatic inflammation and fibrogenesis markers induced by a Western diet supplemented with liquid fructose in LDL-R−/− mice are not associated with a significant impairment of hepatic insulin signalling.

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“…Jia et al [60] also conceived that the regulation of PPAR alpha-responsive genes and the activation of the autophagic pathway were suggested mechanism of lipid and glucose metabolism, which hinted the closely connection of PPAR alpha with autophagy. Baena et al results [62] similarly showed that fatty acid metabolism in short-term supplementation studies was involved in metabolic alterations depended on PPAR alpha inhibition, and the effects of sub-chronic supplementation were related to defective hepatic autophagy. More convincing evidences by Jiao et al [61] were that the PPAR alpha inhibition could weaken autophagy flux, whereas the PPAR alpha activation could upregulate autophagy, and PPAR alpha-mediated induction of autophagy ameliorated liver injury by attenuating inflammatory responses.…”

Section: Newly Participant Of Autophagy Regulation: Pparsmentioning

confidence: 74%

“…In terms of mechanism, our immediate concern is the target genes of PPAR alpha. Autophagy-related genes induced by PPAR alpha activation include ATG2, ATG4, ATG12, ATG16, Pink1, Bnip3, Wipi2, LC3, PI3KCIII, and so on [59][60][61][62] (Table 1). The regulation mechanism of these target genes can be inspired from the following facts.…”

Section: Newly Participant Of Autophagy Regulation: Pparsmentioning

confidence: 99%

The update on transcriptional regulation of autophagy in normal and pathologic cells: A novel therapeutic target

Zhang

Guo

Zhao

et al. 2015

Biomedicine & Pharmacotherapy

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Fructose supplementation impairs rat liver autophagy through mTORC activation without inducing endoplasmic reticulum stress

Cited by 48 publications

References 38 publications

Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice

Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice

The Addition of Liquid Fructose to a Western-Type Diet in LDL-R−/− Mice Induces Liver Inflammation and Fibrogenesis Markers without Disrupting Insulin Receptor Signalling after an Insulin Challenge

The update on transcriptional regulation of autophagy in normal and pathologic cells: A novel therapeutic target

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