Targeting Molecular Mechanisms of Obesity- and Type 2 Diabetes Mellitus-Induced Skeletal Muscle Atrophy with Nerve Growth Factor.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Diabetes Mellitus, Experimental*/metabolism ; Diabetes Mellitus, Experimental*/pathology ; Diabetes Mellitus, Experimental*/complications ; Diabetes Mellitus, Type 2*/metabolism ; Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/pathology ; Muscle, Skeletal*/metabolism ; Muscle, Skeletal*/pathology ; Muscle, Skeletal*/drug effects ; Muscular Atrophy*/metabolism ; Muscular Atrophy*/etiology ; Muscular Atrophy*/pathology ; Nerve Growth Factor*/metabolism ; Obesity*/metabolism ; Obesity*/complications ; Obesity*/pathology; Animals ; Male ; Mice ; Autophagy/drug effects ; Diet, Western ; Mice, Inbred C57BL ; Myostatin/metabolism

Skeletal muscle plays a critical role in metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). Muscle atrophy, characterized by a decrease in muscle mass and function, occurs due to an imbalance between the rates of muscle protein synthesis and degradation. This study aimed to investigate the molecular mechanisms that lead to muscle atrophy in obese and T2DM mouse models. Additionally, the effect of nerve growth factor (NGF) on the protein synthesis and degradation pathways was examined. Male mice were divided into three groups: a control group that was fed a standard chow diet, and two experimental groups that were fed a Western diet. After 8 weeks, the diabetic group was injected with streptozotocin to induce T2DM. Each group was then further divided into NGF-treated or non-treated control group. In the gastrocnemius muscles of the Western diet group, increased expressions of myostatin, autophagy markers, and ubiquitin ligases were observed. Skeletal muscle tissue morphology indicated signs of muscle atrophy in both obese and diabetic mice. The NGF-treated group showed a prominent decrease in the protein levels of myostatin and autophagy markers. Furthermore, the NGF-treated group showed an increased Cyclin D1 level. Western diet-induced obesity and T2DM may be linked to muscle atrophy through upregulation of myostatin and subsequent increase in the ubiquitin and autophagy systems. Moreover, NGF treatment may improve muscle protein synthesis and cell cycling.

Biophys Rev. 2021 Mar 4;13(2):203-219. (PMID: 33927785)
Oncogene. 2007 May 14;26(22):3227-39. (PMID: 17496918)
Arch Endocrinol Metab. 2015 Apr;59(2):148-53. (PMID: 25993678)
Am J Physiol Endocrinol Metab. 2008 May;294(5):E918-27. (PMID: 18334608)
Cells. 2020 Oct 02;9(10):. (PMID: 33023189)
Oxid Med Cell Longev. 2015;2015:684965. (PMID: 26448817)
Biochem Biophys Res Commun. 2019 Jun 25;514(2):407-414. (PMID: 31056256)
Neth J Med. 2013 May;71(4):174-87. (PMID: 23723111)
Mol Biol Cell. 2008 Jun;19(6):2566-78. (PMID: 18367547)
J Endocrinol. 2003 Mar;176(3):425-37. (PMID: 12630927)
Methods Enzymol. 2009;452:199-213. (PMID: 19200884)
Am J Clin Nutr. 2006 Sep;84(3):475-82. (PMID: 16960159)
Nat Commun. 2021 Jan 12;12(1):330. (PMID: 33436614)
Endocrinology. 2003 Dec;144(12):5615-22. (PMID: 14500580)
Chem Biol Interact. 2016 Jan 25;244:49-63. (PMID: 26656244)
Am J Physiol. 1999 Aug;277(2 Pt 2):R601-6. (PMID: 10444569)
Front Cell Dev Biol. 2018 Oct 02;6:128. (PMID: 30333975)
FASEB J. 2001 Aug;15(10):1807-9. (PMID: 11481237)
J Alzheimers Dis. 1998 Mar;1(1):35-44. (PMID: 12214010)
J Musculoskelet Neuronal Interact. 2003 Mar;3(1):8-16. (PMID: 15758361)
J Physiol. 2009 Feb 1;587(3):669-77. (PMID: 19047209)
Am J Physiol Cell Physiol. 2016 Sep 1;311(3):C392-403. (PMID: 27510905)
J Biol Chem. 2000 Dec 22;275(51):40235-43. (PMID: 10976104)
Gene Ther. 2008 Feb;15(3):155-60. (PMID: 18033313)
J Bone Metab. 2020 Aug;27(3):151-165. (PMID: 32911580)
Cell. 2016 Mar 24;165(1):248-248.e1. (PMID: 27015313)
Biochem Biophys Res Commun. 2011 Dec 2;415(4):632-6. (PMID: 22079631)
Nat Commun. 2015 Apr 10;6:6670. (PMID: 25858807)
Lancet. 2017 Jun 3;389(10085):2239-2251. (PMID: 28190580)
Compr Physiol. 2020 Jul 8;10(3):785-809. (PMID: 32940941)
Am J Physiol Endocrinol Metab. 2014 Sep 15;307(6):E469-84. (PMID: 25096180)
Exerc Immunol Rev. 2016;22:94-109. (PMID: 26859514)
J Huazhong Univ Sci Technolog Med Sci. 2012 Aug;32(4):534-539. (PMID: 22886966)
J Neurosci. 2000 Apr 1;20(7):2589-601. (PMID: 10729339)
Exp Cell Res. 2003 Jun 10;286(2):263-75. (PMID: 12749855)
BMC Res Notes. 2012 Sep 20;5:513. (PMID: 22994964)
J Cachexia Sarcopenia Muscle. 2011 Sep;2(3):143-151. (PMID: 21966641)
Mol Vis. 2012;18:758-64. (PMID: 22509106)
Cells. 2021 Aug 13;10(8):. (PMID: 34440852)
J Cell Biochem. 2010 Nov 1;111(4):1059-73. (PMID: 20677217)
Oncogene. 1999 Mar 25;18(12):2055-68. (PMID: 10321730)
Int J Dev Neurosci. 2000 Dec;18(8):869-85. (PMID: 11154856)
Muscle Nerve. 2003 Mar;27(3):370-3. (PMID: 12635125)
Dev Biol. 2005 Jul 1;283(1):58-69. (PMID: 15975431)
Neurosci Lett. 2011 Jul 1;498(1):31-6. (PMID: 21549807)

Keywords: diabetes; muscle atrophy; nerve growth factor; obesity; western diet

Date Created: 20240427 Date Completed: 20240427 Latest Revision: 20240520

20240520

PMC11050157

10.3390/ijms25084307

38673892