Objective: To investigate the effect of high-fat diet (HFD) on respiratory function and its mitochondrial mechanism in mice. Methods: Twenty 4-week-old healthy male C57BL/6 mice were divided by simple random grouping into two groups, 10 mice for each group. Mice were raised with normal diet (
NFD) and HFD for 16 weeks, respectively, and weighed once every two weeks. At the end of the intervention, respiratory parameters were measured by whole-body plethysomography, serum and diaphragm tissue
lipid species were measured, diaphragm tissue was stained to observe diaphragmmatic morphology, muscle fiber phenotype and mitochondrial ultrastructure. Real-time fluorescence quantitative PCR and immunoblotting were used to detect
myosin heavy chain(MHC) and mitochondrial dynamics-related genes and
protein expression. Results: The baseline
body weights of
NFD and HFD mice were (19.17±0.59) and (19.12±0.64) g, respectively, with no statistically significant differences (P=0.857). After 16 weeks of feeding, the
body weight of mice in the HFD group was (41.28±2.21) g, which was higher than
NFD group [(27.14±0.53) g, P<0.001]. The peak inspiratory flow rate, tidal volume and minute ventilation of mice in the HFD group were (5.72±0.64) ml/s, (0.23±0.04) ml and (97.49±21.68) ml, respectively, which were lower than
NFD group [(7.70±1.52) ml/s, (0.31±0.07) ml and (129.99±28.87) ml, respectively, all P values<0.05]. Penh value was 1.16±0.07, which was higher than
NFD group (0.98±0.09, P<0.001). The diaphragmatic
triglyceride content of mice in the HFD group was (20.43±6.36) mmol/mg, which was higher than
NFD group [(11.62±1.78) mmol/mg] (P=0.003), and lipid droplets were deposited in the diaphragm fibers. The percentage of MHC-Ⅰ muscle fibers in the diaphragm of mice in the HFD group was 13.33%±2.95%, which was lower than
NFD group (19.20%±1.23%, P=0.034). The mitochondria of the diaphragm in the
NFD group were arranged in rows with clear structures, while in the HFD group showed swelling, cristae breakage and vacuoles. The relative expression level of mitochondrial fusion
protein 2 in the diaphragm of the HFD group was 0.61±0.16, which was lower than
NFD group (1.28±0.03, P<0.001); the relative expression of mitochondrial
dynamin-related
protein 1 were 1.18±0.06 and 0.91±0.11, respectively, both higher than
NFD group (0.61±0.07 and 0.60±0.04, respectively, P<0.001). Conclusion: HFD impairs respiratory function in mice by the mechanism associated with the MHC-Ⅰ muscle fibers decrease and the mitochondrial dynamics imbalance of diaphragm.