Western Diet-Induced Obesity Does Not Cause Diaphragm Muscle Abnormalities

Abstract

PURPOSE: Obese individuals demonstrate ventilatory abnormalities at rest and during exercise, which may reflect inspiratory (diaphragm) muscle weakness. Several studies have shown diaphragm abnormalities in genetically obese animal models. However, the effects of an obesogenic diet on the diaphragm are not well defined. The purpose of this study was to determine if a Western diet (high-saturated fat, high-sugar: HFHS) causes diaphragm muscle pathology, perhaps related to oxidative stress. METHODS: Adult male Wistar rats were randomly allocated to one of two ad libitum diets for 24 weeks: healthy control (n=8) or HFHS diet (n=8). Diaphragm muscle then underwent i) in vitro contractile function assessment, ii) histology and immunohistochemistry for determination of fibrosis and fiber cross-sectional area (CSA) and iii) analysis of mitochondrial reactive oxygen species (ROS) emission. Data are mean ± SE. RESULTS: We previously reported that HFHS diet did not impair diaphragm maximal specific force or peak power. Alongside this maintenance of contractile function, HFHS-fed rats did not differ in diaphragm muscle interstitial fibrosis (in %: lean 3.4±0.8, HFHS 2.7±1.7), type I fiber CSA (in μm2: lean 1954±121, HFHS 2174±103), type IIa fiber CSA (in μm2: lean 2062±329, HFHS 2412±155), or type IIb/x fiber CSA (in μm2: lean 4165±1232, HFHS 4523±526). Additionally, no shifts in fiber type occurred. Interestingly, HFHS diaphragm demonstrated a trend toward a lower succinate-induced increase in ROS emission (in pmol/min: lean 1.313 ± 0.2, HFHS 0.73 ± 0.2, p = 0.09). Analyses of glutathione and antioxidant enzymes are ongoing. CONCLUSION: A high-saturated fat, high-sugar diet did not induce diaphragm muscle dysfunction or morphological changes. These results, combined with our previous findings of normal contractile function, suggest that intrinsic diaphragm muscle abnormalities do not contribute to breathing difficulties in obesity.