Molecular Mechanisms of Obesity-Induced Osteoporosis and Muscle Atrophy

Abstract

Obesity and osteoporosis are two alarming health disorders prominent among middle and old age populations, and the numbers of those affected by these two disorders are increasing. It is estimated that more than 600 million adults are obese and over 200 million people have osteoporosis worldwide. Interestingly, both of these abnormalities share some common features including a genetic predisposition, and a common origin: bone marrow mesenchymal stromal cells. Obesity is characterized by the expression of leptin, adiponectin, interleukin 6 (IL-6), interleukin 10 (IL-10), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), macrophage colony stimulating factor (M-CSF), growth hormone (GH), parathyroid hormone (PTH), angiotensin II (Ang II), 5-hydroxy-tryptamine (5-HT), Advance glycation end products (AGE), and myostatin, which exert their effects by modulating the signaling pathways within bone and muscle. Chemical messengers (e.g., TNF-α, IL-6, AGE, leptins) that are upregulated or downregulated as a result of obesity have been shown to act as negative regulators of osteoblasts, osteocytes and muscles, as well as positive regulators of osteoclasts. These additive effects of obesity ultimately increase the risk for osteoporosis and muscle atrophy. The aim of this review is to identify the potential cellular mechanisms through which obesity may facilitate osteoporosis, muscle atrophy and bone fractures.

Effects of protein supplementation combined with resistance exercise on body composition and physical function in older adults: a systematic review and meta-analysis

“…3 Mean of the study sample. 4 Two sex-specific comparisons for men and women in the trial conducted by Leenders et al (25) were independently used in the meta-analysis.…”

“…Moreover, among the 17 RCTs, 8 had a sex-specific design for male participants (18,20,25,30,31,33,34,37), with an overall BMI Values are presented as means 6 SDs. 4 Value was estimated or calculated using statistical formulas with the data reported by the authors. 5 Significant within-group difference for control compared with baseline.…”

“…Obese elderly people face high risks of age-related muscle wasting, such as sarcopenia (2), or disease-related muscle loss such as that which occurs in people with diabetes (3). In addition, low-grade chronic and systemic inflammation induced by the expansion of adipose tissue in obese adults may potentially affect muscle protein synthesis (MPS) and induce muscle atrophy (4). Accordingly, sarcopenic obesity-a phenotype recently identified in the obese elderly population-is caused by the underlying additive effect of sarcopenia and obesity and is identified by the coexistence of diminished muscle mass and increased fat mass (FM).…”

SOX6 rs7117858 polymorphism is associated with osteoporosis and obesity‐related phenotypes

“…Thus, genetic markers associated with bone mass also have been linked with obesity phenotypes, supporting shared genetic component for both conditions [11][12][13][14] . Nevertheless, the exact molecular mechanisms shared between these two syndromes are still unclear 16 . Nevertheless, the exact molecular mechanisms shared between these two syndromes are still unclear 16 .…”

“…The genetic correlation between obesity and osteoporosis were also evidenced in a genome-wide bivariate analysis (GWAS) that found some quantitative trait loci shared by FM and BMD 15 . Nevertheless, the exact molecular mechanisms shared between these two syndromes are still unclear 16 .…”