Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity

Abstract

Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis). Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching hypothesis that there is a central role for muscle damage with chronic exposure to an obesity-inducing diet. The inflammatory consequence of diet and muscle dysregulation can result in dysregulated tissue repair and an imbalance toward negative adaptation, resulting in regulatory failure and other musculoskeletal tissue damage. The commonalities support the conclusion that musculoskeletal pathology with MetS should be evaluated in a comprehensive and integrated manner to understand risk for other MSK-related conditions. Implications for conservative management strategies to regulate MetS are discussed, as are future research opportunities.

Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats

“…As an insulin‐sensitive tissue, muscle tissue is responsible for 80–90% of glucose uptake and utilization in the body, thus improvements in muscle metabolism are likely critical to rescuing metabolic health (30). Since we have previously observed disparate changes in muscle with the HFS diet that are speculated to be related to fiber type (31), we evaluated 2 muscles of different fiber type (MG, glycolytic; soleus, oxidative). Unexpectedly, OFS supplementation of a maternal HFS diet had a substantial impact on the expression of genes in both the soleus and the MG muscles.…”

Achilles tendinopathy – pathophysiology: state of the art

“…The pathogenesis is multifactorial and includes overload, related to the increased body mass index, but also systemic factors such as bioactive peptides (eg, chemerin, leptin, adiponectin). These bioactive peptides elicit a chronic and low-grade inflammation, which can give rise to metabolic syndrome 52. Obesity in AT is one factor that should be assessed and treated.…”

“…Advances in our understanding of the pathophysiological pathways of inflammation have provided further insight into its potential role in specific forms of tendon disease 52. Specific circumstances such as extreme mechanical stress on the Achilles tendon in combination with systemic inflammation may potentiate the development of tendinopathy 55…”

Nutritional status of Tajik children and women: Transition towards a double burden of malnutrition

“…Paradoxically, many parts of the world are currently exposed to an overweight and obesity epidemic, with over 39% of adults being overweight worldwide, caused by an energy imbalance between consumption and expenditure (WHO, 2018c). As a consequence, noncommunicable diseases like cardiovascular diseases, diabetes, musculoskeletal disorder, and some cancers are increasing (Collins et al, 2018;Igel, Saunders, & Fins, 2018;Steele et al, 2017). This fast increase in overweight and obesity along with a slow decrease or stagnancy in undernutrition (wasting, stunting, and micronutrient deficiencies) experienced in many low-and middle-income countries (Freire, Silva-Jaramillo, Ramirez-Luzuriaga, Belmont, & Waters, 2014;Haddad, Cameron, & Barnett, 2015;WHO, 2018a) leads to the socalled double burden of malnutrition (Kosaka & Umezaki, 2017) and United Nations Children's Fund [UNICEF], 2010;UNICEF, 2003).…”