Muscle <scp>PGC</scp>‐1α in exercise and fasting‐induced regulation of hepatic <scp>UPR</scp> in mice

Kristensen, Caroline Maag; Jessen, Henrik; Ringholm, Stine; Pilegaard, Henriette

doi:10.1111/apha.13158

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…In muscle cells, the UPR can be induced by metabolic factors (e.g., fatty acid) and exercise-related factors (e.g., PGC-1α) (Woodworth-Hobbs et al, 2017; Kristensen et al, 2018). Recent studies identified UPR markers in regenerating fibers of chronic myositis muscles (Vattemi et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

“…Our recent work (Ding et al, 2018), with data described by others (Nagaraju, 2001; Wiendl et al, 2005), supports the intrinsic immune properties of muscle cells in inflammatory conditions. Despite the description of ER stress in the response to muscle metabolic consequences, acute stressors, and cancer cachexia (Bohnert et al, 2016, 2019; Woodworth-Hobbs et al, 2017; Kristensen et al, 2018), including autoimmune and genetic muscle disorders (Afroze and Kumar, 2017), the role of the individual arms of the UPR in regulating muscle fiber immune function has not been fully explained. Our results with CTX-treated mice provide evidence that the eIF2α and IRE1α arms of the UPR are critical for muscle fiber function during skeletal muscle regeneration.…”

Section: Discussionmentioning

confidence: 99%

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The IRE1α Arm of UPR Regulates Muscle Cells Immune Characters by Restraining p38 MAPK Activation

Gu¹,

Huang²,

Xiao³

et al. 2019

Front. Physiol.

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Skeletal muscle repair and systemic inflammation/immune responses are linked to endoplasmic reticulum stress (ER stress) pathways in myopathic muscle, and muscle cells play an active role in muscular immune reactions by exhibiting immunological characteristics under persistent proinflammation stimuli. Whether ER stress affects the intrinsic immunological capacities of myocytes in the inflammatory milieu, as it does to immune cells, and which arms of the unfolded protein response (UPR) mainly participate in these processes remain mostly unknown. We investigated this issue and showed that inflammatory stimuli can induce the activation of the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) arms of the UPR in myocytes both in vivo and in vitro. UPR stressor administration reversed the increased IFN-γ-induced expression of the MHC-II molecule H2-Ea, the MHC-I molecule H-2Kb, toll-like receptor 3 (TLR3) and some proinflammatory myokines in differentiated primary myotubes in vitro. However, further IRE1α inhibition thoroughly corrected the trend in the UPR stressor-triggered suppression of immunobiological molecules. In IFN-γ-treated myotubes, dramatic p38 MAPK activation was observed under IRE1α inhibitory conditions, and the pharmacological inhibition of p38 reversed the immune molecule upregulation induced by IRE1α inhibition. In parallel, our coculturing system verified that the ovalbumin (OVA) antigen presentation ability of inflamed myotubes to OT-I T cells was enhanced by IRE1α inhibition, but was attenuated by further p38 inhibition. Thus, the present findings demonstrated that p38 MAPK contributes greatly to IRE1α arm-dependent immunobiological suppression in myocytes under inflammatory stress conditions.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The IRE1α Arm of UPR Regulates Muscle Cells Immune Characters by Restraining p38 MAPK Activation

Gu¹,

Huang²,

Xiao³

et al. 2019

Front. Physiol.

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“…The 2 h time point was chosen based on the previous findings that UPR markers were regulated at this time point (Kristensen et al . ). Exercise trained mice performed the last exercise bout 24 h prior to euthanization to prevent acute effects of exercise.…”

Section: Methodsmentioning

confidence: 97%

Impact of liver PGC-1α on exercise and exercise training-induced regulation of hepatic autophagy and mitophagy in mice on HFF

et al. 2018

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Hepatic autophagy has been shown to be regulated by acute exercise and exercise training. Moreover, high‐fat diet‐induced steatosis has been reported to be associated with impaired hepatic autophagy. In addition, autophagy has been shown to be regulated by acute exercise and exercise training in a PGC‐1α dependent manner in skeletal muscle. The aim of this study was to test the hypotheses that high‐fat high‐fructose (HFF) diet changes hepatic autophagy and mitophagy, that exercise training can restore this through a PGC‐1α‐mediated mechanism, and that acute exercise regulates autophagy and mitophagy in the liver. Liver samples were obtained from liver‐specific PGC‐1α KO mice and their littermate Lox/Lox mice fed a HFF diet or a control diet for 13 weeks. The HFF mice were either exercise trained (ExT) on a treadmill the final 5 weeks or remained sedentary (UT). In addition, half of each group performed at the end of the intervention an acute 1 h exercise bout. HFF resulted in increased hepatic BNIP3 dimer and Parkin protein, while exercise training increased BNIP3 total protein without affecting the elevated BNIP3 dimer protein. In addition, exercise training reversed a HFF‐induced increase in hepatic LC3II/LC3I protein ratio, as well as a decreased PGC‐1α mRNA level. Acute exercise increased hepatic PGC‐1α mRNA in HFF UT mice only. In conclusion, this indicates that exercise training in part reverses a HFF‐induced increase in hepatic autophagy and capacity for mitophagy in a PGC‐1α‐independent manner. Moreover, HFF may blunt acute exercise‐induced regulation of hepatic autophagy.

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“…Elevated hepatic LC3II/I ratio, but not SQSTM1, was observed immediately after exercise in both WT and skeletal muscle-specific PGC1α overexpressing mice, a response that returned to baseline 2 h postexercise in both groups (52). Similarly, liver-specific PGC1αKO and WT mice also displayed an increased hepatic LC3II/I ratio after exercise (53).…”

Section: Effects Of Endurance Exercise On Liver Autophagymentioning

confidence: 99%