Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice

Ghareghani, Parvin; Shanaki, Mehrnoosh; Ahmadi, Saeideh; Khoshdel, Alireza; Rezvan, Neda; Meshkani, Reza; Delfan, Maryam; Gorgani‐Firuzjaee, Sattar

doi:10.1016/j.orcp.2017.01.004

Cited by 51 publications

(42 citation statements)

References 30 publications

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“…Here we show that adiponectin was able to counteract the decrease in autophagy which occurred in response to HIHG treatment of L6 cells. Our observations are in keeping with a growing body of recent studies which have shown that promoting autophagy by various approaches is beneficial in terms of improving insulin sensitivity (Wang et al 2015, Zhu et al 2016, Ghareghani et al 2017, Li et al 2017, Rosa-Caldwell et al 2017. For example, using a model of palmitate-induced insulin resistance, it was shown that stress-inducible protein Sestrin2 (Sesn2) up-regulation maintained insulin sensitivity and glucose metabolism via AMPK-dependent autophagic activation (Li et al 2017).…”

Section: Discussionsupporting

confidence: 87%

“…Importantly, we recently demonstrated that adiponectin stimulates autophagic flux in skeletal muscle and that increased autophagy contributed to insulin-sensitizing anti-diabetic effects (Liu et al 2015. Others have now also shown that boosting autophagy via a variety of approaches can enhance insulin sensitivity in skeletal muscle and other tissues (Wang et al 2015, Zhu et al 2016, Ghareghani et al 2017, Li et al 2017, Rosa-Caldwell et al 2017 and vice versa that decreased the levels of skeletal muscle autophagy were observed in type 2 diabetes and upon aging (Zhang et al 2016, Moller et al 2017, Zhou et al 2017.…”

Section: Introductionmentioning

confidence: 94%

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Adiponectin improves insulin sensitivity via activation of autophagic flux

Ahlstrom

Rai

Chakma

et al. 2017

Journal of Molecular Endocrinology

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Skeletal muscle insulin resistance is known to play an important role in the pathogenesis of diabetes, and one potential causative cellular mechanism is endoplasmic reticulum (ER) stress. Adiponectin mediates anti-diabetic effects via direct metabolic actions and by improving insulin sensitivity, and we recently demonstrated an important role in stimulation of autophagy by adiponectin. However, there is limited knowledge on crosstalk between autophagy and ER stress in skeletal muscle and in particular how they are regulated by adiponectin. Here, we utilized the model of high insulin/glucose (HIHG)-induced insulin resistance, determined by measuring Akt phosphorylation (T308 and S473) and glucose uptake in L6 skeletal muscle cells. HIHG reduced autophagic flux measured by LC3 and p62 Western blotting and tandem fluorescent RFP/GFP-LC3 immunofluorescence (IF). HIHG also induced ER stress assessed by thioflavin T/KDEL IF, pIRE1, pPERK, peIF2α and ATF6 Western blotting and induction of a GRP78-mCherry reporter. Induction of autophagy by adiponectin or rapamycin attenuated HIHG-induced ER stress and improved insulin sensitivity. The functional significance of enhanced autophagy was validated by demonstrating a lack of improved insulin sensitivity in response to adiponectin in autophagy-deficient cells generated by overexpression of dominant negative mutant of Atg5. In summary, adiponectin-induced autophagy in skeletal muscle cells alleviated HIHG-induced ER stress and insulin resistance.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 94%

Adiponectin improves insulin sensitivity via activation of autophagic flux

Ahlstrom

Rai

Chakma

et al. 2017

Journal of Molecular Endocrinology

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“…Recent studies confirmed that exercise is beneficial in NAFLD due to increased autophagy (56–58). Aerobic endurance training improves NAFLD features via miR‐33‐dependent autophagy induction in HFD‐fed mice (59). Moreover, irisin, muscle‐derived myokines following exercise, stimulates AMPK‐dependent autophagy in the liver (60).…”

Section: Discussionmentioning

confidence: 99%

Long‐term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy‐lysosomal machinery

Pi¹,

Liu²,

Chen³

et al. 2019

FASEB j.

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Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent diseases worldwide. Exercise is a first‐line therapy and an important preventive measure for patients with NAFLD, but the underlying mechanisms are not clear. C57BL/6 mice were fed a high‐fat diet (HFD) and subjected to 12 wk swimming exercise. Exercise protected against hepatic lipid accumulation and alleviated hepatocyte damage in HFD mice. Tandem mass tag—based quantitative proteomic analyses and ingenuity pathway analysis revealed that exercise down‐regulated fatty acid‐binding protein (FABP) 1 signaling pathway, which was most closely associated with lipid metabolism. Moreover, exercise significantly decreased FABP1 expression, and liver‐specific overexpression of FABP1 abolished the protective effect of exercise in NAFLD mice. Specifically, exercise significantly increased autophagic flux via restoring lysosomal function, including lysosomal proteolysis and lysosomal acidification maintenance, contributing to enhancement in autophagic clearance and subsequently alleviation of hepatic steatosis. Conversely, Fabp1 overexpression in the mouse liver blocked the protective effect of exercise via inhibiting autophagy flux. The present study identified FABP1 inhibition‐mediated replenishment of the autophagy‐lysosomal machinery as a novel endogenous mechanism whereby long‐term exercise improves lipid homeostasis and ameliorates hepatic steatosis in NAFLD.—Pi, H., Liu, M., Xi, Y., Chen, M., Tian, L., Xie, J., Chen, M., Wang, Z., Yang M., Yu, Z., Zhou, Z., Gao, F. Long‐term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy‐lysosomal machinery. FASEB J. 33, 11870‐11883 (2019). http://www.fasebj.org

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“…Accordingly, exercise has been shown to augment acute autophagic activity in SkM and in several other tissues. These include adipose tissue, heart, liver, pancreatic β cells, peripheral blood mononuclear cells (PBMCs), and brain [ 77 , 78 , 79 , 80 ].…”

Section: Exercise and Autophagymentioning

confidence: 99%

Irisin and Autophagy: First Update

Pesce

Ballerini

Paolucci

et al. 2020

IJMS

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Aging and sedentary life style are considered independent risk factors for many disorders. Under these conditions, accumulation of dysfunctional and damaged cellular proteins and organelles occurs, resulting in a cellular degeneration and cell death. Autophagy is a conserved recycling pathway responsible for the degradation, then turnover of cellular proteins and organelles. This process is a part of the molecular underpinnings by which exercise promotes healthy aging and mitigate age-related pathologies. Irisin is a myokine released during physical activity and acts as a link between muscles and other tissues and organs. Its main beneficial function is the change of subcutaneous and visceral adipose tissue into brown adipose tissue, with a consequential increase in thermogenesis. Irisin modulates metabolic processes, acting on glucose homeostasis, reduces systemic inflammation, maintains the balance between resorption and bone formation, and regulates the functioning of the nervous system. Recently, some of its pleiotropic and favorable properties have been attributed to autophagy induction, posing irisin as an important regulator of autophagy by exercise. This review article proposes to bring together for the first time the “state of the art” knowledge regarding the effects of irisin and autophagy. Furthermore, treatments on relation between exercise/myokines and autophagy have been also achieved.

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Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice

Cited by 51 publications

References 30 publications

Adiponectin improves insulin sensitivity via activation of autophagic flux

Adiponectin improves insulin sensitivity via activation of autophagic flux

Long‐term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy‐lysosomal machinery

Irisin and Autophagy: First Update

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