Abstract
A strong relationship exists between increased inflammatory cytokines and muscle insulin resistance in obesity. This study focused on identifying a relationship between metabolic propensity and myostatin expression in muscle and spleen cells in response to high-fat diet intake. Using a comparative approach, we analyzed the effects of high-fat diet intake on myostatin and follistatin expression, spleen cell composition, and potential cytokine expression in high-fat diet induced obesity (HFDIO) resistant (SWR/J) and susceptible (C57BL/6) mice models. Results demonstrated overall increased myostatin expression in muscle following high-fat diet intake in HFDIO-susceptible mice, while myostatin expression levels decreased initially in muscle from high-fat diet fed resistant mice. In HFDIO-resistant mice, myostatin expression decreased in spleen, while myostatin increased in spleen tissue from HFDIO-susceptible mice. Proinflammatory cytokine (IL-17, IL-1β, and IFNγ) potential increased in splenocytes from HFDIO-susceptible mice. In comparison, C57BL/6 mice fed a high-fat diet exhibited higher frequencies of CD4+/CD44hi and CD8+/CD44hi cells in the spleen compared to control fed mice. Together, these results suggest that susceptibility to high-fat diet induced obesity could be influenced by local myostatin activity in a tissue-specific manner and that splenocytes exhibit differential cytokine production in a strain-dependent manner. This study sets the stage for future investigations into the interactions between growth, inflammation, and metabolism.
Highlights
The pathophysiology of obesity and type 2 diabetes is complex and is associated with environmental and lifestyle risk factors that include a sedentary lifestyle and an overweight condition
SWR mice are resistant to high-fat diet induced obesity Over the 12-wk feeding trial, C57BL/6 mice fed the high-fat diet consistently gained weight, while the other treatment groups failed to exhibit significant weight gain (Fig. 1a)
Blood glucose levels were elevated 2.45-fold in C57BL/6 mice fed the high-fat diet compared to mice fed the control diet (236650 mg/dl compared to 96610 mg/dl)
Summary
The pathophysiology of obesity and type 2 diabetes is complex and is associated with environmental and lifestyle risk factors that include a sedentary lifestyle and an overweight condition. Transgenic mice expressing muscle-specific MSTN propeptide exhibit 20% faster growth and 44% more muscle mass than wild-type controls, but maintain normal adipose tissue [6]. The mechanisms regulating the interactions between the inflammatory response and muscle insulin sensitivity are still not fully elucidated. It has been known for some time that high-fat diets can generally compromise protective immune responses [16,17]. The intent of the current study was to evaluate the interactions between high-fat diet intake, MSTN expression, and spleen cell population dynamics in two strains of mice exhibiting differential responses to dietary intake. To the authors’ knowledge, this is the first report of differential MSTN expression in different strains of mice, as well as the first report of MSTN expression in spleen and leukocytes in mice
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