Effect and mechanism of muscle injury on liver lipid metabolism in Duchenne muscular dystrophy mice

ZHANG Ziling; LU Qian; XU Dengqiu; YU Qinwei; JIANG Zhenzhou

doi:10.11665/j.issn.1000-5048.20210612

Journal of China Pharmaceutical University > 2021 > 52(6): 735-741. > DOI: 10.11665/j.issn.1000-5048.20210612

ZHANG Ziling, LU Qian, XU Dengqiu, YU Qinwei, JIANG Zhenzhou. Effect and mechanism of muscle injury on liver lipid metabolism in Duchenne muscular dystrophy mice[J]. Journal of China Pharmaceutical University, 2021, 52(6): 735-741. DOI: 10.11665/j.issn.1000-5048.20210612

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Effect and mechanism of muscle injury on liver lipid metabolism in Duchenne muscular dystrophy mice

1.
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009
2.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009
3.
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81773827), the Scholar of the 14th batch of "Six Talents Peak" High-Level Talent Selection (No.SWYY-094), the "Double First-Class" University Project (No.CPU2018GY33), and the Postgraduate Research Practice Innovation Program of Jiangsu Province (No.KYCX19_0763)

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Received Date: May 17, 2021
Revised Date: October 27, 2021

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Abstract

Abstract

Duchene muscular dystrophy (DMD) is a serious progressive muscular dystrophy.Reports in recent years about abnormal lipid in DMD patients have increased, yet little attention has been paid to liver lipid.This study aimed to explore the effect of dystrophin gene defect on liver lipid synthesis.7-week-old mdx male mice were used as DMD model.The conditions of liver function, liver lipid accumulation and liver lipid synthesis were determined through liver tissue morphological examination, blood biochemical examination, and detection of hepatic gene and protein expression.The results showed that lipid droplets in liver of mdx mice increased significantly.The contents of total cholesterol and triglyceride in liver, aspartate aminotransferase and alanine aminotransferase in serum increased.The gene and protein expression of hepatic lipid synthesis-related enzymes such as fatty acid synthase, acetyl CoA carboxylase, and sterol regulatory element binding protein 1-c were up-regulated.These results showed accumulation of liver lipid in 7-week-old mdx male mice.
- Duchene muscular dystrophy,
- skeletal muscle injury,
- liver lipid accumulation,
- lipid synthesis

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[1]	. Liver Int，2021，41（4）：683-691.
[2]	Fan LY，Sweet DR，Prosdocimo DA，et al. Muscle Krüppel-like factor 15 regulates lipid flux and systemic metabolic homeostasis［J］. J Clin Invest，2021，131（4）：e139496.
[3]	Moon JS，Yoon JS，Won KC，et al. The role of skeletal muscle in development of nonalcoholic fatty liver disease［J］. Diabetes Metab J，2013，37（4）：278-285.
[4]	Srikanthan P，Hevener AL，Karlamangla AS. Sarcopenia exacerbates obesity-associated insulin resistance and dysglycemia：findings from the National Health and Nutrition Examination Survey III［J］. PLoS One，2010，5（5）：e10805.
[5]	Huang JS，Glauber M，Qiu ZH，et al. The influence of skeletal muscle on the regulation of liver：body mass and liver regeneration［J］. Am J Pathol，2012，180（2）：575-582.
[6]	Van Der Windt DJ，Sud V，Zhang HJ，et al. The effects of physical exercise on fatty liver disease［J］. Gene Expr，2018，18（2）：89-101.
[7]	Takahashi H，Kotani K，Tanaka K，et al. Therapeutic approaches to nonalcoholic fatty liver disease：exercise intervention and related mechanisms［J］. Front Endocrinol （Lausanne），2018，9：588-604.
[8]	Duan D，Goemans N，Takeda S，et al. Duchenne muscular dystrophy［J］. Nat Rev Dis Primers，2021，7（1）：13-32.
[9]	Cirak S，Feng L，Anthony K，et al. Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy［J］. Mol Ther，2012，20（2）：462-467.
[10]	Nathwani RA，Pais S，Reynolds TB，et al. Serum alanine aminotransferase in skeletal muscle diseases［J］. Hepatology，2005，41（2）：380-382.
[11]	White Z，Hakim CH，Theret M，et al. High prevalence of plasma lipid abnormalities in human and canine Duchenne and Becker muscular dystrophies depicts a new type of primary genetic dyslipidemia［J］. J Clin Lipidol，2020，14（4）：459-469.
[12]	Jeon BN，Kim YS，Choi WI，et al. Kr-pok increases FASN expression by modulating the DNA binding of SREBP-1c and Sp1 at the proximal promoter［J］. J Lipid Res，2012，53（4）：755-766.
[13]	Wakil SJ，Abu-Elheiga LA. Fatty acid metabolism：target for metabolic syndrome［J］. J Lipid Res，2009，50 SupplS：138-143.
[14]	Mei Lk，Wei QQ，Zhang HB，et al. Research progress in acetyl-CoA carboxylase inhibitors［J］ J China Pharm Univ（中国药科大学学报），2019，50（3）：253-264.
[15]	Abu-Elheiga L，Almarza-Ortega DB，Baldini A，et al. Human acetyl-CoA carboxylase 2. Molecular cloning，characterization，chromosomal mapping，and evidence for two isoforms［J］. J Biol Chem，1997，272（16）：10669-10677.
[16]	Chen GX，Liang GS，Ou J，et al. Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver［J］. Proc Natl Acad Sci U S A，2004，101（31）：11245-11250.
[17]	Schomaker S，Potter D，Warner R，et al. Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments［J］. PLoS One，2020，15（5）：e0229753.
[18]	Wagner KR. The elusive promise of myostatin inhibition for muscular dystrophy［J］. Curr Opin Neurol，2020，33（5）：621-628.
[19]	Dasarathy S. Cause and management of muscle wasting in chronic liver disease［J］. Curr Opin Gastroenterol，2016，32（3）：159-165.
[20]	Garcia PS，Cabbabe A，Kambadur R，et al. Brief-reports：elevated myostatin levels in patients with liver disease：a potential contributor to skeletal muscle wasting［J］. Anesth Analg，2010，111（3）：707-709.
[21]	Hanai T，Shiraki M，Ohnishi S，et al. Rapid skeletal muscle wasting predicts worse survival in patients with liver cirrhosis［J］. Hepatol Res，2016，46（8）：743-751.

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