期刊论文详细信息
Lipids in Health and Disease
Saturated fatty acid palmitate-induced insulin resistance is accompanied with myotube loss and the impaired expression of health benefit myokine genes in C2C12 myotubes
Hengyi Xiao1  Zhe Wang1  Xiaojuan Han1  Xu Wang1  Jie Zhang1  Chunfen Mo1  Dandan Wei1  Ming Yang1 
[1] Department of Geriatrics, Regenerative Medicine Research Center, Laboratory of Stem cell biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Keyuan 4-1, Gaopeng Street, High-tech Zone, Chengdu 610041, China
关键词: Insulin resistance;    Myokine;    Myotube loss;    Palmitate;   
Others  :  1160021
DOI  :  10.1186/1476-511X-12-104
 received in 2013-05-01, accepted in 2013-07-02,  发布年份 2013
PDF
【 摘 要 】

Background

Excessive circular fatty acid, particlarly saturated fatty acid, can result in insulin resistance in skeletal muscle, but other adverse effects of fatty acid accumulation in myocytes remain unclear.

Methods

Differentiated C2C12 myotubes were used. The effects of palmitate on cell viability, glucose uptake, gene expression and myotube loss were evaluated by MTT assay, 2NBDG uptake, qRT-PCR, Western Blot and crystal staining-based myotube counting, respectively. In some expreiments, oleate was administrated, or the inhibitors of signaling pathways were applied.

Results

Palmitate-induced cellular insulin resistance was clarified by the reduced Akt phosphorylation, glucose uptake and Glut4 expression. Palmitate-caused myotube loss was clearly observed under microscope and proved by myotube counting and expression analysis of myotube marker genes. Moreover, palmitate-induced transcriptional suppression of three health benefit myokine genes (FNDC5, CTRP15 and FGF21) was found, and the different involvement of p38 and PI3K in the transcription of these genes was noticed.

Conclusions

Palmitate-induced insulin resistance accompanys myotube loss and the impaired expression of FNDC5, CTRP15 and FGF21genes in C2C12 myotubes. These results provide novel evidence indicating the negative role of high concentration of palmitate in myotubes.

【 授权许可】

   
2013 Yang et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150410092200571.pdf 1316KB PDF download
Figure 6. 105KB Image download
Figure 5. 65KB Image download
Figure 4. 149KB Image download
Figure 3. 150KB Image download
Figure 2. 112KB Image download
Figure 1. 63KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】
  • [1]DeFronzo RA, Ferrannini E: Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14(3):173-94.
  • [2]Jove M, et al.: Palmitate-induced interleukin 6 production is mediated by protein kinase C and nuclear-factor kappaB activation and leads to glucose transporter 4 down-regulation in skeletal muscle cells. Endocrinology 2005, 146(7):3087-95.
  • [3]Boden G: Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 1997, 46(1):3-10.
  • [4]Roden M, et al.: Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 1996, 97(12):2859-65.
  • [5]Dimopoulos N, et al.: Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells. Biochem J 2006, 399(3):473-81.
  • [6]Holland WL, et al.: Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 2007, 5(3):167-79.
  • [7]Dey D, et al.: Involvement of novel PKC isoforms in FFA induced defects in insulin signaling. Mol Cell Endocrinol 2006, 246(1–2):60-4.
  • [8]Yu C, et al.: Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002, 277(52):50230-6.
  • [9]Deng YT, et al.: Suppression of free fatty acid-induced insulin resistance by phytopolyphenols in C2C12 mouse skeletal muscle cells. J Agric Food Chem 2012, 60(4):1059-66.
  • [10]Long YC, Zierath JR: AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest 2006, 116(7):1776-83.
  • [11]Brown DM, Parr T, Brameld JM: Myosin heavy chain mRNA isoforms are expressed in two distinct cohorts during C2C12 myogenesis. J Muscle Res Cell Motil 2012, 32(6):383-90.
  • [12]Vescovo G, et al.: Skeletal muscle myosin heavy chain expression in rats with monocrotaline-induced cardiac hypertrophy and failure. Relation to blood flow and degree of muscle atrophy. Cardiovasc Res 1998, 39(1):233-41.
  • [13]Randall WB, et al.: Docosahexaenoic acid protects muscle cells from palmitate-induced atrophy. ISRN Obesity; 2012.
  • [14]Fanzani A, et al.: Molecular and cellular mechanisms of skeletal muscle atrophy: an update. J Cachexia Sarcopenia Muscle 2012, 3(3):163-79.
  • [15]Goldbach-Mansky R: Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1. Clin Exp Immunol 2012, 167(3):391-404.
  • [16]Zhang L, et al.: Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. FASEB J 2011, 25(5):1653-63.
  • [17]Pedersen BK: The diseasome of physical inactivity–and the role of myokines in muscle–fat cross talk. J Physiol 2009, 587(Pt 23):5559-68.
  • [18]Seldin MM, et al.: Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 2012, 287(15):11968-80.
  • [19]Bostrom P, et al.: A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012, 481(7382):463-8.
  • [20]Kim KH, et al.: Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine. Nat Med 2013, 19(1):83-92.
  • [21]Cheng Q, et al.: Visfatin inhibits apoptosis of pancreatic beta-cell line, MIN6, via the mitogen-activated protein kinase/phosphoinositide 3-kinase pathway. J Mol Endocrinol 2011, 47(1):13-21.
  • [22]Jove M, et al.: Palmitate induces tumor necrosis factor-alpha expression in C2C12 skeletal muscle cells by a mechanism involving protein kinase C and nuclear factor-kappaB activation. Endocrinology 2006, 147(1):552-61.
  • [23]Li N, et al.: D-galactose induces necroptotic cell death in neuroblastoma cell lines. J Cell Biochem 2011, 112(12):3834-44.
  • [24]Zhou Q, et al.: Evidence for adipose-muscle cross talk: opposing regulation of muscle proteolysis by adiponectin and Fatty acids. Endocrinology 2007, 148(12):5696-705.
  • [25]Chavez JA, Summers SA: Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes. Arch Biochem Biophys 2003, 419(2):101-9.
  • [26]Wang X, et al.: Insulin resistance accelerates muscle protein degradation: activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology 2006, 147(9):4160-8.
  • [27]Gaster M, Rustan AC, Beck-Nielsen H: Differential utilization of saturated palmitate and unsaturated oleate: evidence from cultured myotubes. Diabetes 2005, 54(3):648-56.
  • [28]Lilienbaum A: Relationship between the proteasomal system and autophagy. Int J Biochem Mol Biol 2013, 4(1):1-26.
  • [29]Sadiq F, et al.: Amino acids and insulin act additively to regulate components of the ubiquitin-proteasome pathway in C2C12myotubes. BMC Mol Biol 2007, 8:23. BioMed Central Full Text
  • [30]Sheng X, et al.: Different degree in proteasome malfunction has various effects on root growth possibly through preventing cell division and promoting autophagic vacuolization. PLoS One 2012, 7(9):e45673.
  • [31]Kadotani A, et al.: Different impacts of saturated and unsaturated free fatty acids on COX-2 expression in C(2)C(12) myotubes. Am J Physiol Endocrinol Metab 2009, 297(6):E1291-303.
  文献评价指标  
  下载次数:490次 浏览次数:80次