Journal Article

Aging- and obesity-related peri-muscular adipose tissue accelerates muscle atrophy

Oike, Yuichi, Xie, Peiyu, Zhu, Shunshun, Miyata, Keishi, Zhao, Jiabin, Terada, Kazutoyo, Torigoe, Daisuke, Tian, Zhe, Sato, Michio, Horiguchi, Haruki, Kadomatsu, Tsuyoshi, Sugizaki, Taichi

2019

Overview

Sarcopenia due to loss of skeletal muscle mass and strength leads to physical inactivity and decreased quality of life. The number of individuals with sarcopenia is rapidly increasing as the number of older people increases worldwide, making this condition a medical and social problem. Some patients with sarcopenia exhibit accumulation of peri-muscular adipose tissue (PMAT) as ectopic fat deposition surrounding atrophied muscle. However, an association of PMAT with muscle atrophy has not been demonstrated. Here, we show that PMAT is associated with muscle atrophy in aged mice and that atrophy severity increases in parallel with cumulative doses of PMAT. We observed severe muscle atrophy in two different obese model mice harboring significant PMAT relative to respective control non-obese mice. We also report that denervation-induced muscle atrophy was accelerated in non-obese young mice transplanted around skeletal muscle with obese adipose tissue relative to controls transplanted with non-obese adipose tissue. Notably, transplantation of obese adipose tissue into peri-muscular regions increased nuclear translocation of FoxO transcription factors and upregulated expression FoxO targets associated with proteolysis (Atrogin1 and MuRF1) and cellular senescence (p19 and p21) in muscle. Conversely, in obese mice, PMAT removal attenuated denervation-induced muscle atrophy and suppressed upregulation of genes related to proteolysis and cellular senescence in muscle. We conclude that PMAT accumulation accelerates age- and obesity-induced muscle atrophy by increasing proteolysis and cellular senescence in muscle.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Accumulation / Adipose tissue / Adipose Tissue - metabolism / Adipose Tissue - pathology / Age / Aging / Aging (Biology) / Aging - genetics / Aging - metabolism / Aging - pathology / Animals / Atrophy / Biology and Life Sciences / Body fat / Cellular Senescence - genetics / Complications and side effects / Denervation / Development and progression / Disease / Disease Models, Animal / DNA binding proteins / Forkhead Box Protein O1 - genetics / Forkhead protein / Genes / Health aspects / Homeostasis / Humans / Immunology / Inflammation / Laboratory animals / Medicine and Health Sciences / Metabolism / Mice / Mice, Obese / Muscle Proteins - genetics / Muscle, Skeletal - metabolism / Muscle, Skeletal - pathology / Muscles / Muscular atrophy / Muscular Atrophy - genetics / Muscular Atrophy - metabolism / Muscular Atrophy - pathology / Musculoskeletal system / Nuclear transport / Obesity / Obesity - genetics / Obesity - metabolism / Obesity - pathology / Older people / Physiological aspects / Proteolysis / Quality of Life / Sarcopenia / Sarcopenia - genetics / Sarcopenia - metabolism / Sarcopenia - pathology / Senescence / Skeletal muscle / SKP Cullin F-Box Protein Ligases - genetics / Social conditions / Surgery / Transcription factors / Translocation / Transplantation / Transplants & implants / Tripartite Motif Proteins - genetics / Ubiquitin-Protein Ligases - genetics