Sparc, an EPS-induced gene, modulates the extracellular matrix and mitochondrial function via ILK/AMPK pathways in C2C12 cells

Melouane, Aicha; Yoshioka, Mayumi; Kanzaki, Makoto; St‐Amand, Jonny

doi:10.1016/j.lfs.2019.05.070

Cited by 32 publications

(30 citation statements)

References 83 publications

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“…SPARC is also implicated in metabolism [44,45], cancer [46] and inflammatory [47] homeostasis. Importantly, for the SM, a key metabolic tissue and the key organ for the exercise performance, SPARC represents an important element for its development [28] and function [7].…”

Section: Discussion and Interpretationmentioning

confidence: 99%

“…Within the exercise context, functional genomics studies (mainly but not only in the energy metabolism context [3]) have identified genes related to physical activity among which we have SPARC/Sparc. Indeed, beyond the known implications of SPARC in wound healing and tissue repair [4,5], this gene was characterized (for the first time) as an exercise-induced gene [6] and also as an electrical pulse stimulation (considered as an in vitro model of exercise)-induced gene in muscular cells [7]. Moreover, SPARC secretion is induced by exercise [8][9][10] after which the concentrations of myokines (including SPARC, interleukin 6 and fibroblast growth factor) increase in the circulation [11].…”

Section: Secreted Protein Acidic and Rich In Cysteine As An Exercise-induced Genementioning

confidence: 99%

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Exercise Training of Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Mice Suggests That Exercise-Induced Muscle Phenotype Changes Are SPARC-Dependent

et al. 2020

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We previously identified secreted protein acidic and rich in cysteine (Sparc) as an exercise-induced gene in young and elderly individuals. Via this animal experiment, we aim to identify selected implications of SPARC mainly within the muscle in the contexts of exercise. Mice were divided into eight groups based on three variables (age, genotype and exercise): Old (O) or young (Y) × Sparc knock-out (KO) or wild-type (WT) × sedentary (Sed) or exercise (Ex). The exercised groups were trained for 12 weeks at the lactate threshold (LT) speed (including 4 weeks of adaptation period) and all mice were sacrificed afterwards. Body and selected tissues were weighed, and lactate levels in different conditions measured. Expression of skeletal muscle (SM) collagen type I alpha 1 chain (COL1A1) and mitochondrially encoded cytochrome c oxidase I (MT-CO1) in addition to SM strength (grip power) were also measured. Ageing increased the body and white adipose tissue (WAT) weights but decreased SM weight percentage (to body weight) and MT-CO1 expression (in WT). Exercise increased SM COL1A1 in WT mice and MT-CO1 expression, as well as weight percentage of the tibialis anterior muscle, and decreased WAT weight (trend). Compared to WT mice, Sparc KO mice had lower body, muscle and WAT weights, with a decrease in SM MT-CO1 and COL1A1 expression with no genotype effect on lactate levels in all our blood lactate measures. Sparc KO effects on body composition, adiposity and metabolic patterns are toward a reduced WAT and body weight, but with a negative metabolic and functional phenotype of SM. Whereas such negative effects on SM are worsened with ageing, they are relatively improved by exercise. Importantly, our data suggest that the exercise-induced changes in the SM phenotype, in terms of increased performance (metabolic, strength and development), including lactate-induced changes, are SPARC-dependent.

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Section: Discussion and Interpretationmentioning

confidence: 99%

Section: Secreted Protein Acidic and Rich In Cysteine As An Exercise-induced Genementioning

confidence: 99%

Exercise Training of Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Mice Suggests That Exercise-Induced Muscle Phenotype Changes Are SPARC-Dependent

et al. 2020

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“…Similar to IL-15 and irisin, the expression of osteonectin (also known as SPARC) can be induced by exercise [99]. Current studies have only uncovered the activities of osteonectin in undifferentiated myoblasts, where it upregulated mitochondrial proteins such as ubiquinol-cytochrome c reductase core protein II (UQCRC2) and succinate dehydrogenase subunit (SDHB) probably through AMPK activation [100,101]. This osteonectindependent elevation of mitochondrial protein is important to myogenesis [100].…”

Section: Osteonectin/secreted Protein Acidic and Rich In Cysteine (Sparc)mentioning

confidence: 99%

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Pang¹,

Chan²,

Chan³

2021

Antioxidants

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Mitochondria are the cellular powerhouses that generate adenosine triphosphate (ATP) to substantiate various biochemical activities. Instead of being a static intracellular structure, they are dynamic organelles that perform constant structural and functional remodeling in response to different metabolic stresses. In situations that require a high ATP supply, new mitochondria are assembled (mitochondrial biogenesis) or formed by fusing the existing mitochondria (mitochondrial fusion) to maximize the oxidative capacity. On the other hand, nutrient overload may produce detrimental metabolites such as reactive oxidative species (ROS) that wreck the organelle, leading to the split of damaged mitochondria (mitofission) for clearance (mitophagy). These vital processes are tightly regulated by a sophisticated quality control system involving energy sensing, intracellular membrane interaction, autophagy, and proteasomal degradation to optimize the number of healthy mitochondria. The effective mitochondrial surveillance is particularly important to skeletal muscle fitness because of its large tissue mass as well as its high metabolic activities for supporting the intensive myofiber contractility. Indeed, the failure of the mitochondrial quality control system in skeletal muscle is associated with diseases such as insulin resistance, aging, and muscle wasting. While the mitochondrial dynamics in cells are believed to be intrinsically controlled by the energy content and nutrient availability, other upstream regulators such as hormonal signals from distal organs or factors generated by the muscle itself may also play a critical role. It is now clear that skeletal muscle actively participates in systemic energy homeostasis via producing hundreds of myokines. Acting either as autocrine/paracrine or circulating hormones to crosstalk with other organs, these secretory myokines regulate a large number of physiological activities including insulin sensitivity, fuel utilization, cell differentiation, and appetite behavior. In this article, we will review the mechanism of myokines in mitochondrial quality control and ROS balance, and discuss their translational potential.

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“…It has been previously observed that SPARC can interact and activate AMPK 31,47 . The activation of AMPK then phosphorylates SREBP blocking its nuclear translocation.…”

Section: Resultsmentioning

confidence: 98%

SPARC inhibition accelerates NAFLD‐associated hepatocellular carcinoma development by dysregulating hepatic lipid metabolism

Onorato

Fiore

Bayo

et al. 2021

Liver International

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Background and aims Non‐alcoholic fatty liver (NAFLD) and its more serious form non‐alcoholic steatohepatitis increase risk of hepatocellular carcinoma (HCC). Lipid metabolic alterations and its role in HCC development remain unclear. SPARC (Secreted Protein, Acidic and Rich in Cysteine) is involved in lipid metabolism, NAFLD and diabetes, but the effects on hepatic lipid metabolism and HCC development is unknown. The aim of this study was to evaluate the role of SPARC in HCC development in the context of NAFLD. Methods Primary hepatocyte cultures from knockout (SPARC−/−) or wild‐type (SPARC+/+) mice, and HepG2 cells were used to assess the effects of free fatty acids on lipid accumulation, expression of lipogenic genes and de novo triglyceride (TG) synthesis. A NAFLD‐HCC model was stabilized on SPARC−/− or SPARC+/+ mice. Correlations among SPARC, lipid metabolism‐related gene expression patterns and clinical prognosis were studied using HCC gene expression dataset. Results SPARC−/− mice increases hepatic lipid deposits over time. Hepatocytes from SPARC−/− mice or inhibition of SPARC by an antisense adenovirus in HepG2 cells resulted in increased TG deposit, expression of lipid‐related genes and nuclear translocation of SREBP1c. Human HCC database analysis revealed that SPARC negatively correlated with genes involved in lipid metabolism, and with poor survival. In NAFLD‐HCC murine model, the absence of SPARC accelerates HCC development. RNA‐seq study revealed that pathways related to lipid metabolism, cellular detoxification and proliferation were upregulated in SPARC−/− tumour‐bearing mice. Conclusions The absence of SPARC is associated with an altered hepatic lipid metabolism, and an accelerated NAFLD‐related HCC development.

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Sparc, an EPS-induced gene, modulates the extracellular matrix and mitochondrial function via ILK/AMPK pathways in C2C12 cells

Cited by 32 publications

References 83 publications

Exercise Training of Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Mice Suggests That Exercise-Induced Muscle Phenotype Changes Are SPARC-Dependent

Exercise Training of Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Mice Suggests That Exercise-Induced Muscle Phenotype Changes Are SPARC-Dependent

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

SPARC inhibition accelerates NAFLD‐associated hepatocellular carcinoma development by dysregulating hepatic lipid metabolism

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