(Dys)regulation of Protein Metabolism in Skeletal Muscle of Humans With Obesity

Abstract

Studies investigating the proteome of skeletal muscle present clear evidence that protein metabolism is altered in muscle of humans with obesity. Moreover, muscle quality (i.e., strength per unit of muscle mass) appears lower in humans with obesity. However, relevant evidence to date describing the protein turnover, a process that determines content and quality of protein, in muscle of humans with obesity is quite inconsistent. This is due, at least in part, to heterogeneity in protein turnover in skeletal muscle of humans with obesity. Although not always evident at the mixed-muscle protein level, the rate of synthesis is generally lower in myofibrillar and mitochondrial proteins in muscle of humans with obesity. Moreover, alterations in the synthesis of protein in muscle of humans with obesity are manifested more readily under conditions that stimulate protein synthesis in muscle, including the fed state, increased plasma amino acid availability to muscle, and exercise. Current evidence supports various biological mechanisms explaining impairments in protein synthesis in muscle of humans with obesity, but this evidence is rather limited and needs to be reproduced under more defined experimental conditions. Expanding our current knowledge with direct measurements of protein breakdown in muscle, and more importantly of protein turnover on a protein by protein basis, will enhance our understanding of how obesity modifies the proteome (content and quality) in muscle of humans with obesity.

Energy metabolism in skeletal muscle cells from donors with different body mass index

“…Not much research has been done to understand the effect of obesity on amino acid uptake, protein synthesis, and turnover in human skeletal muscle cells. Recent research suggests that protein synthesis could be altered in skeletal muscle in individuals with obesity ( Beals et al, 2019 ; Freitas and Katsanos, 2022 ). However, there is a large heterogeneity when it comes to protein metabolism in skeletal muscle from subjects with obesity.…”

Investigating effects of sodium beta‐hydroxybutyrate on metabolism in placebo‐controlled, bilaterally infused human leg with focus on skeletal muscle protein dynamics

“…There is evidence that tissue blood flow and BHB uptake depends on the local metabolic rate in, for example, the central nervous system and exercising vs nonexercising muscle (Mikkelsen et al, 2015 ); these effects probably involve NO‐induced vasodilation (Avogaro et al, 1999 ) and prostaglandin I2 release (Avogaro et al, 1996 ). Reduced blood flow may be involved in the development of sarcopenia in elderly (Zempo et al, 2017 ) or obese people (Freitas & Katsanos, 2022 ) and increased muscle blood flow has in the postexercise recovery phase been shown to increase protein synthesis (Biolo et al, 1995 ). However, blood flow‐restricted resistance exercise has also been shown to augment protein synthesis (Sieljacks et al, 2019 ).…”

People with obesity exhibit losses in muscle proteostasis that are partly improved by exercise training

“…The pathogenesis of obesity and type II diabetes is underpinned by defects in metabolic homeostasis, including hyperinsulinemia and insulin resistance [1]. However, there is uncertainty regarding the effects of obesity and insulin resistance on protein metabolism in human muscle [2]. Gains in muscle mass can coincide with the elevation in fat mass associated with obesity, but people with obesity are also more susceptible to age-related muscle loss (i.e., sarcopenic obesity).…”