Comparative analysis of high-fat diet and intermittent hypoxia impacts on C57BL/6N and C57BL/6J mouse strains

Abstract

Background: Obstructive sleep apnoea, featured with intermittent hypoxia (IH), is highly associated with obesity. Mouse inbred line C57BL/6N and C57BL/6J are both widely used for research. We performed a comparison of the two mouse strains to identify the different functional impacts of high-fat-diet-induced obesity and IH. Methods: Male 4-week-old mice of C57BL/6N and C57BL/6J strains were used. Half were fed with standard diet and the other half were fed with high-fat diet (LabDiet; St Louis [MO], USA) to induce obesity. At the age of 13 weeks, mice of both strains were subjected to intermittent normoxia or IH (cycles of 10% O2 for 60 seconds followed by 21% O2 for another 60 seconds, 30 hypoxic events per hour; BioSpherix, USA) 8 hours per day. After 1 week of exposure, mice were sacrificed (n=4 in each group). Blood samples, subcutaneous and epididymal adipose tissues were collected. enzyme-linked immunosorbent assay was applied for the measurement of serum lipid and adipose tissue inflammatory markers. Results: All mice fed with high-fat diet exhibited obesity. C57BL/6J mice showed slight decrease of body weight gain after IH exposure in the obese group. Serum lipid levels increased the obese group of both strains. IH led to significant reduction of low- and high-density lipoprotein and total cholesterol levels in lean C57BL/6J mice only. In subcutaneous and visceral adipose tissue, IH led to significant elevation of IL-6 level in C57BL/6J mice only. Conclusion: The genetic difference between the C57BL/6N and C57BL/6J mice affects the interaction between metabolism and IH. The effect of high-fat diet may be more obvious in C57BL/6N mice, whereas the C57BL/6J mice may be more sensitive to IH. Therefore, the impact of background substrain should be considered before designing the experimental model.