Dieckol-Attenuated High-Fat Diet Induced Muscle Atrophy by Modulating Muscular Deposition of Lipid Droplets.

Kyung-A Byun,Kuk Hui Son,Kyunghee Byun,Chul-Hyun Park,Seyeon Oh,Myeongjoo Son,Seung Eon Oh

doi:10.3390/nu13093160

Kyung-A Byun, Kuk Hui Son + Show 5 more

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https://doi.org/10.3390/nu13093160

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Abstract

An excessive fat diet induces intramuscular fat deposition that accumulates as a form of lipid droplet (LD) and leads to lipotoxicity, including muscle atrophy or decreasing muscle strength. Lipotoxicity depends on the number of LDs, subcellular distribution (intermyofibrillar, IMF, LDs or subsarcolemmal, SS), and fiber type-specific differences (type I or type II fiber) as well as the size of LD. Ecklonia cava extracts (ECE), which is known to increase peroxisome proliferator-activated receptor alpha (PPAR-α), which leads to decreasing expression level of perilipin2 (PLIN2). PLIN2 is involved in modulating the size of LDs. This study shows that ECE and dieckol could decrease PLIN2 expression and decrease the size and number of LDs in the muscle of high-fat diet (HF)-fed animals and lead to attenuating muscle atrophy. Expression level of PPAR-α was decreased, and PLIN2 was increased by HF. ECE and dieckol increased PPAR-α expression and decreased PLIN2. The diameter of LDs was increased in high-fat diet condition, and it was decreased by ECE or dieckol treatment. The number of LDs in type II fibers/total LDs was increased by HF and it was decreased by ECE or dieckol. The SS LDs were increased, and IMF LDs were decreased by HF. ECE or dieckol decreased SS LDs and increased IMF LDs. The ECE or dieckol attenuated the upregulation of muscle atrophy-related genes including Murf1, Atrogin-1, and p53 by HF. ECE or dieckol increased the cross-sectional area of the muscle fibers and grip strength, which were decreased by HF. In conclusion, ECE or dieckol decreased the size of LDs and modulated the contribution of LDs to less toxic ones by decreasing PLIN2 expression and thus attenuated muscle atrophy and strength, which were induced by HF.

Highlights

Intramyocellular lipid (IMCL), which refers to the accumulation of toxic lipids in the myocytes, arises from the increasing uptake of fatty acids (FA) and decreasing removal of FA by decreasing FA oxidation [1]
The expression level of CD36 in the muscle was significantly increased by high-fat diet (HF), and it was significantly decreased by the Ecklonia cava extracts (ECE) or dieckol treatment (Figure 1A,B and Figure S1A)
The expression level of p53 was significantly increased by HF, and it was significantly decreased by the ECE or dieckol treatment (Figure 3C)

Summary

Introduction

Intramyocellular lipid (IMCL), which refers to the accumulation of toxic lipids in the myocytes, arises from the increasing uptake of fatty acids (FA) and decreasing removal of FA by decreasing FA oxidation [1]. CD36, or FA translocase, participates in almost 70% of the total FA uptake [5]. The expression of CD36 is increased by high-lipid diet feeding and leads to increasing FA uptake in the skeletal muscle [6]. Fat accumulates as a form of lipid droplets (LDs) in the skeletal muscle. LD is a dynamic organelle formed from a phospholipid monolayer that encloses a core of lipids like triacylglycerols (TGs) [7]. Not all LDs in the muscle are related to lipotoxicity, since

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