Palmitate-Induced Inflammation and Myotube Atrophy in C2C12 Cells Are Prevented by the Whey Bioactive Peptide, Glycomacropeptide.

Abstract

BACKGROUND:

Metabolic diseases are often associated with muscle atrophy and heightened inflammation. The whey bioactive compound, glycomacropeptide (GMP), has been shown to exhibit anti-inflammatory properties and therefore may have potential therapeutic efficacy in conditions of skeletal muscle inflammation and atrophy.

OBJECTIVES:

The purpose of this study was to determine the role of GMP in preventing lipotoxicity-induced myotube atrophy and inflammation.

METHODS:

C2C12 myoblasts were differentiated to determine the effect of GMP on atrophy and inflammation and to explore its mechanism of action in evaluating various anabolic and catabolic cellular signaling nodes. We also used a lipidomic analysis to evaluate muscle sphingolipid accumulation with the various treatments. Palmitate (0.75 mM) in the presence and absence of GMP (5 μg/mL) was used to induce myotube atrophy and inflammation and cells were collected over a time course of 6-24 h.

RESULTS:

After 24 h of treatment, GMP prevented the palmitate-induced decrease in the myotube area and myogenic index and the increase in the TLR4-mediated inflammatory genes tumor necrosis factor-α and interleukin 1β. Moreover, phosphorylation of Erk1/2, and gene expression of myostatin, and the E3 ubiquitin ligases, FBXO32, and MuRF1 were decreased with GMP treatment. GMP did not alter palmitate-induced ceramide or diacylglycerol accumulation, muscle insulin resistance, or protein synthesis.

CONCLUSIONS:

In summary, GMP prevented palmitate-induced inflammation and atrophy in C2C12 myotubes. The GMP protective mechanism of action in muscle cells during lipotoxic stress may be related to targeting catabolic signaling associated with cellular stress and proteolysis but not protein synthesis.

• Authors: Naomi Mmp de Hart, Jonathan J Petrocelli, Rebekah J Nicholson, Elena M Yee, Patrick J Ferrara, Eric D Bastian, Loren S Ward, Brent L Petersen, Scott A Summers, Micah J Drummond
• Journal: The Journal of nutrition (J Nutr) Vol. 153 Issue 10 Pg. 2915-2928 (10 2023) ISSN: 1541-6100 [Electronic] United States
• PMID: 37652286 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.

Chemical References

• caseinomacropeptide
• Palmitates
• Peptide Fragments

Topics

• Humans
• Whey (metabolism)
• Palmitates (toxicity, metabolism)
• Muscle Fibers, Skeletal (metabolism)
• Muscle, Skeletal
• Muscular Atrophy (chemically induced, prevention & control)
• Peptide Fragments
• Inflammation (metabolism)