Gax suppresses chemerin/CMKLR1‐induced preadipocyte biofunctions through the inhibition of Akt/mTOR and ERK signaling pathways

Jiang, Yuxin; Liu, Ping; Jiao, Wenlin; Meng, Juan; Jiao, Feng

doi:10.1002/jcp.25918

Cited by 26 publications

(19 citation statements)

References 40 publications

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“…To explore the mechanism of chemerin promoting osteogenic differentiation, we detected the downstream molecules of chemerin signaling (Figure S4a, b; Inci et al, 2016; Jiang et al, 2018). We found Akt signaling decreased in Rarres2 −/− mice bone (Figure 6a, b) and increased in TG mice bone (Figure 6c, d).…”

Section: Resultsmentioning

confidence: 99%

Chemerin located in bone marrow promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β‐catenin axis in mice

Zhang

Huang

et al. 2021

Journal Cellular Physiology

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Chemerin, a secreted protein mainly produced by adipocytes and hepatocytes, plays a variety of roles in endocrine or paracrine signaling. As reported in human epidemiology, chemerin was correlated with osteoporosis. And the previous in vitro study found that chemerin knockdown promoted osteogenesis and inhibited adipogenesis. However, the function of chemerin in bone metabolism and the underlying mechanism remains unclear. In this study, we uncovered the in vivo function of chemerin in bone homeostasis. We discovered that in obese mice, chemerin was increased in serum, while decreased in the bone marrow; and the chemerin expression in bone tissue was positively correlated with osteogenic genes. To further investigate the function of chemerin in bone metabolism, we generated chemerin deficiency and overexpression mice. We found bone mass and osteogenesis were decreased in chemerin deficiency mice, while were increased in chemerin overexpression mice. Furthermore, we observed that the chemerin expression increased during osteogenic differentiation of MSCs. Besides, we verified that chemerin promoted osteogenic differentiation in C3H10T1/2 cells and BMSCs through Akt/Gsk3β/β‐catenin axis. Treatment with Akt inhibitor (MK2206) abolished the promoting effect of chemerin on osteogenic differentiation and active β‐catenin. Together, our results suggest chemerin in bone marrow, not in serum, promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β‐catenin axis. Chemerin may serve as a therapeutic strategy for osteoporosis.

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Section: Resultsmentioning

confidence: 99%

Chemerin located in bone marrow promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β‐catenin axis in mice

Zhang

Huang

et al. 2021

Journal Cellular Physiology

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“…Note that Sal B lifted p‐ERK to activate the MEK‐ERK pathway and increase TAZ expression. The MEK‐ERK signalling pathway has been intensively investigated in regulating cells differentiation . Jaiswal et al have suggested that the commitment of human MSCs into osteogenic or adipogenic lineages was governed by activation or inhibition of ERK1/2, respectively .…”

Section: Discussionmentioning

confidence: 99%

Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis through MEK‐ERK pathway

Wang

et al. 2019

J Cellular Molecular Medi

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Salvianolic acid B (Sal B), a major bioactive component of Chinese herb, was identified as a mediator for bone metabolism recently. The aim of this study is to investigate the underlying mechanisms by which Sal B regulates osteogenesis and adipogenesis. We used MC3T3‐E1 and 3T3‐L1 as the study model to explore the changes of cell differentiation induced by Sal B. The results indicated that Sal B at different concentrations had no obvious toxicity effects on cell proliferation during differentiation. Furthermore, Sal B facilitated osteogenesis but inhibited adipogenesis by increasing the expression of transcriptional co‐activator with PDZ‐binding motif (TAZ). Accordingly, TAZ knock‐down offset the effects of Sal B on cell differentiation into osteoblasts or adipocytes. Notably, the Sal B induced up‐expression of TAZ was blocked by U0126 (the MEK‐ERK inhibitor), rather than LY294002 (the PI3K‐Akt inhibitor). Moreover, Sal B increased the p‐ERK/ERK ratio to regulate the TAZ expression as well as the cell differentiation. In summary, this study suggests for the first time that Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis by activating MEK‐ERK signalling pathway, which provides evidence for Sal B to be used as a potential therapeutic agent for the management of bone diseases.

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“…2007 ). The activation of chemerin-CMKLR1 axis facilitates the proliferation and differentiation of preadipocytes by inducing the AKT-mTOR and ERK signalling cascade ( Jiang et al . 2018 ).…”

Section: The Role Of Chemerin In Energy Balance Regulation and Obesitmentioning

confidence: 99%

“…Concomitant with the enhancement of preadipocyte differentiation, chemerin overexpression upregulates VEGF that promotes vascular endothelial cell proliferation, differentiation and angiogenesis in the cultured cells. Moreover, the vascular intensity in the fat pad is increased by the overexpression of chemerin ( Jiang et al . 2018 ), suggesting that chemerin boosts angiogenic potential of fat tissues.…”

Section: The Role Of Chemerin In Energy Balance Regulation and Obesitmentioning

confidence: 99%

Chemerin: a multifaceted adipokine involved in metabolic disorders

Helfer

2018

Journal of Endocrinology

242

208

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Metabolic syndrome is a global public health problem and predisposes individuals to obesity, diabetes and cardiovascular disease. Although the underlying mechanisms remain to be elucidated, accumulating evidence has uncovered a critical role of adipokines. Chemerin, encoded by the gene Rarres2, is a newly discovered adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism. In humans, local and circulating levels of chemerin are positively correlated with BMI and obesity-related biomarkers. In this review, we discuss both peripheral and central roles of chemerin in regulating body metabolism. In general, chemerin is upregulated in obese and diabetic animals. Previous studies by gain or loss of function show an association of chemerin with adipogenesis, glucose homeostasis, food intake and body weight. In the brain, the hypothalamus integrates peripheral afferent signals including adipokines to regulate appetite and energy homeostasis. Chemerin increases food intake in seasonal animals by acting on hypothalamic stem cells, the tanycytes. In peripheral tissues, chemerin increases cell expansion, inflammation and angiogenesis in adipose tissue, collectively resulting in adiposity. While chemerin signalling enhances insulin secretion from pancreatic islets, contradictory results have been reported on how chemerin links to obesity and insulin resistance. Given the association of chemerin with obesity comorbidities in humans, advances in translational research targeting chemerin are expected to mitigate metabolic disorders. Together, the exciting findings gathered in the last decade clearly indicate a crucial multifaceted role for chemerin in the regulation of energy balance, making it a promising candidate for urgently needed pharmacological treatment strategies for obesity.

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Gax suppresses chemerin/CMKLR1‐induced preadipocyte biofunctions through the inhibition of Akt/mTOR and ERK signaling pathways

Cited by 26 publications

References 40 publications

Chemerin located in bone marrow promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β‐catenin axis in mice

Chemerin located in bone marrow promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β‐catenin axis in mice

Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis through MEK‐ERK pathway

Chemerin: a multifaceted adipokine involved in metabolic disorders

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