Myonectin inhibits adipogenesis in 3T3-L1 preadipocytes by regulating p38 MAPK pathway
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In current times, obesity is a major health problem closely associated with metabolic disease such as diabetes, dyslipidemia, and cardiovascular disease. The direct cause of obesity is known as an abnormal increase in fat cell size and the adipocyte pool. Hyperplasia, the increase in number of adipocytes, results from adipogenesis in which preadipocytes differentiate into mature adipocytes. Adipogenesis is regulated by local and systemic cues that alter transduction pathways and subsequent control of adipogenic transcription factors. Therefore, the regulation of adipogenesis is an important target for preventing obesity. Myonectin, a member of the CTRP family, is a type of myokine released by skeletal muscle cells. Although several studies have shown that myonectin is associated with lipid metabolism, the role of myonectin during adipogenesis is not known. Here, we demonstrate the role of myonectin during adipocyte differentiation of 3T3-L1 cells. We found that myonectin inhibits the adipogenesis of 3T3-L1 preadipocytes with a reduction in the expression of adipogenic transcription factors such as C/EBPα, β and PPARγ. Furthermore, we show that myonectin has an inhibitory effect on adipogenesis through the regulation of the p38 MAPK pathway and CHOP. These findings suggest that myonectin may be a novel therapeutic target for the prevention of obesity.
Abstract
In current times, obesity is a major health problem closely associated with metabolic disease such as diabetes, dyslipidemia, and cardiovascular disease. The direct cause of obesity is known as an abnormal increase in fat cell size and the adipocyte pool. Hyperplasia, the increase in number of adipocytes, results from adipogenesis in which preadipocytes differentiate into mature adipocytes. Adipogenesis is regulated by local and systemic cues that alter transduction pathways and subsequent control of adipogenic transcription factors. Therefore, the regulation of adipogenesis is an important target for preventing obesity. Myonectin, a member of the CTRP family, is a type of myokine released by skeletal muscle cells. Although several studies have shown that myonectin is associated with lipid metabolism, the role of myonectin during adipogenesis is not known. Here, we demonstrate the role of myonectin during adipocyte differentiation of 3T3-L1 cells. We found that myonectin inhibits the adipogenesis of 3T3-L1 preadipocytes with a reduction in the expression of adipogenic transcription factors such as C/EBPα, β and PPARγ. Furthermore, we show that myonectin has an inhibitory effect on adipogenesis through the regulation of the p38 MAPK pathway and CHOP. These findings suggest that myonectin may be a novel therapeutic target for the prevention of obesity.
참고문헌 (41)
- Spiegelman BM, "Obesity and the regulation of energy balance", Cell, 104, pp.531~543 (2001)
- Arner P, "Fat cell turnover in humans", Biochem Biophys Res Commun, 396, pp.101~104 (2010)
- Seldin MM, "Myonectin(CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis", J Biol Chem, 287, pp.11968~11980 (2012)
- Mi Q, "Circulating C1q", TNFrelated protein isoform 15 is a marker for the presence of metabolic syndrome, 2019, pp.35, e3085~
- Farmer SR, "Transcriptional control of adipocyte formation", Cell Metab, 4, pp.263~273 (2006)
- Chang E, "Natural products and obesity : a focus on the regulation of mitotic clonal expansion during Adipogenesis", Molecules, 24, pp.1157~ (2019)
- Rosen ED, "Adipocyte differentiation from the inside out", Nat Rev Mol Cell Biol, 7, pp.885~896 (2006)
- Koh YK, "Lipin1 is a key factor for the maturation and maintenance of adipocytes in the regulatory network with CCAAT", enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma 2, 2008, pp.283, 34896~34906
- Takeuchi K, "Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis", Am J Physiol Endocrinol Metab, 296, pp.E1195~E1209 (2009)
- Jones JR, "Deletion of PPAR gamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance", Proc Natl Acad Sci U S A, 102, pp.6207~6212 (2005)
- Tang QQ, "Sequential gene promoter interactions of C", EBPbeta, C, Biochem Biophys Res Commun, pp.2004, 319[DOI]
- Darlington GJ, "C", EBP alpha : a critical regulator of genes governing integrative metabolic processes, 1995, pp.5, 565~570
- Koerner A, "Adipocytokines : leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come", Best Pract Res Clin Endocrinol Metab, 19, pp.525~546 (2005)
- Kim H, "(-)-Epigallocatechin gallate suppresses adipocyte differentiation through the MEK", ERK and PI3K, Cell Biol Int, pp.2012, 36[DOI]
- Hardie DG, "AMP-activated protein kinase : an energy sensor that regulates all aspects of cell function", Genes Dev, 25, pp.1895~1908 (2011)
- Huang B, "Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferatoractivated receptor-gamma(PPARgamma)and AMP-activated protein kinase(AMPK)pathways", J Agric Food Chem, 59, pp.3666~3673 (2011)
- Nakae J, "The forkhead transcription factor Foxo1 regulates adipocyte differentiation", Dev Cell, 4, pp.119~129 (2003)
- Chen YY, "Methyl cinnamate inhibits adipocyte differentiation via activation of the CaMKK2-AMPK pathway in 3T3-L1 preadipocytes", J Agric Food Chem, 60, pp.955~963 (2012)
- Bennett CN, "Regulation of Wnt signaling during adipogenesis", J Biol Chem, 277, pp.30998~31004 (2002)
- Kim WK, "Myostatin inhibits brown adipocyte differentiation via regulation of Smad3-mediated beta-catenin stabilization", Int J Biochem Cell Biol, 44, pp.327~334 (2012)
- Bost F, "The role of MAPKs in adipocyte differentiation and obesity", Biochimie, 87, pp.51~56 (2005)
- Pearson G, "Mitogenactivated protein(MAP)kinase pathways : regulation and physiological functions", Endocr Rev, 22, pp.153~183 (2001)
- Johnson GL, "Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases", Science, 298, pp.1911~1912 (2002)
- Hu J, "ERK1 and ERK2activate CCAAAT", enhancer-binding protein-beta-dependent gene transcription in response to interferon-gamma, 2001, ~
- Zick Y, "Insulin resistance : a phosphorylation-based uncoupling of insulin signaling", Trends Cell Biol, 11, pp.437~441 (2001)
- Hirosumi J, "A central role for JNK in obesity and insulin resistance", Nature, 420, pp.333~336 (2002)
- Engelman JA, "Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis", J Biol Chem, 273, pp.32111~32120 (1998)
- Hata K, "Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis", Mol Biol Cell, 14, pp.545~555 (2003)
- Engelman JA, "Constitutively active mitogen-activated protein kinase kinase 6(MKK6)or salicylate induces spontaneous 3T3-L1 adipogenesis", J Biol Chem, 274, pp.35630~35638 (1999)
- Ho IC, "A potential role for the nuclear factor of activated T cells family of transcriptional regulatory proteins in adipogenesis", Proc Natl Acad Sci U S A, 95, pp.15537~15541 (1998)
- Patel NG, "Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation", Diabetes, 52, pp.43~50 (2003)
- Aouadi M, "Inhibition of p38MAPK increases adipogenesis from embryonic to adult stages", Diabetes, 55, pp.281~289 (2006)
- Yang TT, "Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases", Mol Cell Biol, 22, pp.3892~3904 (2002)
- Tamura K, "Requirement for p38alpha in erythropoietin expression : a role for stress kinases in erythropoiesis", Cell, 102, pp.221~231 (2000)
- Wang XZ, "Stress-induced phosphorylation and activation of the transcription factor CHOP(GADD 153)by p38 MAP Kinase", Science, 272, pp.1347~1349 (1996)
- Batchvarova N, "Inhibition of adipogenesis by the stress-induced protein CHOP(Gadd153)", EMBO J, 14, pp.4654~4661 (1995)
- Kim WK, "Effects of leptin on lipid metabolism and gene expression of differentiationassociated growth factors and transcription factors during differentiation and maturation of 3T3-L1 preadipocytes", Endocr J, 55, pp.827~837 (2008)
- Kim WK, "Regulation of adipogenic differentiation by LAR tyrosine phosphatase in human mesenchymal stem cells and 3T3-L1 preadipocytes", J Cell Sci, 122, pp.4160~4167 (2009)
- Kim EY, "Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity", J Lipid Res, 53, pp.1864~1876 (2012)
- Monir Hossain, "Sinapic acid induces the expression of thermogenic signature genes and lipolysis through activation of PKA", CREB signaling in brown adipocytes, 2020, pp.53(3), 142~147[DOI]
- Mai Thi Nguyen, "MiR-183-5p induced by saturated fatty acids regulates the myogenic differentiation by directly targeting FHL1 in C2C12 myoblasts", BMB Reports, 53(11), pp.605~610 (2020), 생화학분자생물학회[DOI]