CREG1 improves the capacity of the skeletal muscle response to exercise endurance via modulation of mitophagy

Song, Hee-Jung; Tian, Xiaoxiang; Liú, Dan; Liu, Meili; Liu, Yanxia; Liu, Jing; Mei, Zhu; Cao, Yan; Han, Yaling

doi:10.1080/15548627.2021.1904488

Cited by 25 publications

(20 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies revealed that TFEB, along with PGC-1α, is an important regulator of exercise-induced mitochondrial biogenesis in skeletal muscle [39]. Another factor, the secreted glycoprotein CREG1, has recently been suggested to modulate mitophagy and improve exercise performance [40]. In this study, exercise increased the expression of TFEB and CREG1 in the controls and TLR4m mice (Figure 4E,F), which suggests that TFEB and CREG1 are not regulators for TLR4-mediated exercise adaptations.…”

Section: Discussionmentioning

confidence: 47%

TLR4-Mediated Inflammatory Responses Regulate Exercise-Induced Molecular Adaptations in Mouse Skeletal Muscle

Fujiyoshi

Egawa

Kurogi

et al. 2022

IJMS

View full text Add to dashboard Cite

Endurance exercise induces various adaptations that yield health benefits; however, the underlying molecular mechanism has not been fully elucidated. Given that it has recently been accepted that inflammatory responses are required for a specific muscle adaptation after exercise, this study investigated whether toll-like receptor (TLR) 4, a pattern recognition receptor that induces proinflammatory cytokines, is responsible for exercise-induced adaptations in mouse skeletal muscle. The TLR4 mutant (TLR4m) and intact TLR4 control mice were each divided into 2 groups (sedentary and voluntary wheel running) and were housed for six weeks. Next, we removed the plantaris muscle and evaluated the expression of cytokines and muscle regulators. Exercise increased cytokine expression in the controls, whereas a smaller increase was observed in the TLR4m mice. Mitochondrial markers and mitochondrial biogenesis inducers, including peroxisome proliferator-activated receptor beta and heat shock protein 72, were increased in the exercised controls, whereas this upregulation was attenuated in the TLR4m mice. In contrast, exercise increased the expression of molecules such as peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and glucose transporter 4 in both the controls and TLR4m mice. Our findings indicate that exercise adaptations such as mitochondrial biogenesis are mediated via TLR4, and that TLR4-mediated inflammatory responses could be involved in the mechanism of adaptation.

show abstract

Section: Discussionmentioning

confidence: 47%

TLR4-Mediated Inflammatory Responses Regulate Exercise-Induced Molecular Adaptations in Mouse Skeletal Muscle

Fujiyoshi

Egawa

Kurogi

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…These results indicate that CREG1 treatment stimulates UCP1 expression in mice at thermoneutrality. Moreover, the expression of autophagic marker proteins was examined in the IBAT and RWAT, because autophagy plays a critical role in lipid metabolism (Singh et al, 2009) and the involvement of CREG1 in autophagy has been reported in previous studies (Liu et al, 2021;Song et al, 2021). There was no difference in the protein levels of Beclin-1, sequestosome 1 (SQSTM1/ p62), and microtubule-associated protein 1 light chain 3B (LC3B) in the IBAT between the PBS and CREG1 groups (Figure 3d).…”

Section: Ucp1 Expression In Adipose Tissues At Thermoneutralitymentioning

confidence: 60%

“…Recently, several groups reported that CREG1 plays a role in the regulation of autophagy. Song et al (2021) have demonstrated that CREG1 is involved in mitophagy modulation in skeletal muscles. Liu et al (2021) have also demonstrated that CREG1 promotes autophagy and lysosome-mediated protein degradation in human hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

CREG1 improves diet‐induced obesity via uncoupling protein 1‐dependent manner in mice

et al. 2022

View full text Add to dashboard Cite

Thermogenic brown and beige adipocytes express uncoupling protein 1 (UCP1) and stimulate energy metabolism, protecting against obesity and metabolic diseases such as type 2 diabetes and hyperlipidemia. Cellular repressor of E1Astimulated genes 1 (CREG1) can stimulate thermogenic fat formation, induce UCP1, and reduce diet-induced obesity (DIO) in mice at normal room temperature. In this study, we investigated the effect of CREG1 administration and the importance of UCP1 in DIO inhibition under thermoneutral conditions at 30°C, which attenuate thermogenic fat formation. Interestingly, subcutaneous administration of recombinant CREG1 protein via an osmotic pump in C57BL/6J mice for four weeks increased UCP1 expression in interscapular brown adipose tissue (IBAT), inhibited visceral white fat hypertrophy with partial browning, and reduced DIO compared to that in PBS-treated mice. The mRNA expression of energy metabolism-related genes was significantly increased in the IBAT of CREG1treated mice compared to that in PBS-treated mice. In contrast, adipocyte-specific overexpression of CREG1 failed to improve DIO in UCP1-knockout mice at thermoneutrality. Our results indicate the therapeutic potential of CREG1 administration for obesity under thermogenic fat-attenuating conditions and highlight the indispensable role of UCP1 in the DIO-inhibitory effect of CREG1.

show abstract

“…Although cardiomyocyte differentiation from precursor cells was found to use a mitophagy pathway not involving Parkin and those precursor cells contained no detectable PRKN RNA before or after differentiation [ 76 ], we found preferential expression of PRKN in myoblasts vs. heterologous cell types. Moreover, the Parkin pathway has been implicated in mitophagy in myoblasts as well as in SkM [ 77 ]. It is likely that the mixed enhancer and promoter chromatin region that we found in myoblasts near the 3′ end of PRKN and the myoblast-specific AS transcription in this region upregulate PRKN transcription, as generally observed for some other enhancer regions that generate unidirectional poly(A) + lncRNAs [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetics of Mitochondria-Associated Genes in Striated Muscle

2021

View full text Add to dashboard Cite

Striated muscle has especially large energy demands. We identified 97 genes preferentially expressed in skeletal muscle and heart, but not in aorta, and found significant enrichment for mitochondrial associations among them. We compared the epigenomic and transcriptomic profiles of the 27 genes associated with striated muscle and mitochondria. Many showed strong correlations between their tissue-specific transcription levels, and their tissue-specific promoter, enhancer, or open chromatin as well as their DNA hypomethylation. Their striated muscle-specific enhancer chromatin was inside, upstream, or downstream of the gene, throughout much of the gene as a super-enhancer (CKMT2, SLC25A4, and ACO2), or even overlapping a neighboring gene (COX6A2, COX7A1, and COQ10A). Surprisingly, the 3′ end of the 1.38 Mb PRKN (PARK2) gene (involved in mitophagy and linked to juvenile Parkinson’s disease) displayed skeletal muscle/myoblast-specific enhancer chromatin, a myoblast-specific antisense RNA, as well as brain-specific enhancer chromatin. We also found novel tissue-specific RNAs in brain and embryonic stem cells within PPARGC1A (PGC-1α), which encodes a master transcriptional coregulator for mitochondrial formation and metabolism. The tissue specificity of this gene’s four alternative promoters, including a muscle-associated promoter, correlated with nearby enhancer chromatin and open chromatin. Our in-depth epigenetic examination of these genes revealed previously undescribed tissue-specific enhancer chromatin, intragenic promoters, regions of DNA hypomethylation, and intragenic noncoding RNAs that give new insights into transcription control for this medically important set of genes.

show abstract

CREG1 improves the capacity of the skeletal muscle response to exercise endurance via modulation of mitophagy

Cited by 25 publications

References 68 publications

TLR4-Mediated Inflammatory Responses Regulate Exercise-Induced Molecular Adaptations in Mouse Skeletal Muscle

TLR4-Mediated Inflammatory Responses Regulate Exercise-Induced Molecular Adaptations in Mouse Skeletal Muscle

CREG1 improves diet‐induced obesity via uncoupling protein 1‐dependent manner in mice

Epigenetics of Mitochondria-Associated Genes in Striated Muscle

Contact Info

Product

Resources

About