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A6407 - Differential Effects of High Fat Diet and Intermittent Hypoxia on C57BL/6N and C57BL/6J Mouse Strains
Author Block: M. Ge, S. Yeung, J. C. Mak, M. S. Ip; Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
Background: Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with obesity. Mouse inbred line C57BL/6N (6N) and C57BL/6J (6J) are widely used for OSA research purpose. We aimed to investigate whether the genetic differences of the two strains of mice have any potential impact upon high fat diet-induced obesity and IH in the mouse model.
Methods: We used four-week old male mice of 6N and 6J strain. Equal numbers (n = 8) of mice were randomized to standard diet (SD) group or high fat (HF) diet (LabDiet; St. Louis, MO, USA) group. At the age of 13-week, mice were subjected to intermittent normoxia (IN) or IH (cycles of 10% O2 for 60 seconds followed by another 60 seconds of 21% O2, 30 hypoxic events per hour, 8 hours per day; BioSpherix, USA) for one week. Blood samples, subcutaneous and epididymal adipose tissues were collected at the time after sacrifice. Serum lipids and adipose tissue inflammatory marker interleukin (IL)-6 were measured.
Results: All mice fed with HF diet exhibited obesity. 6N mice had more fat mass percentage to body weight in comparison to 6J mice in HF group but not affected by IH exposure, while IH significantly reversed the HF diet-induced elevation of fat mass in 6J mice. Furthermore, obese 6J mice showed a trend of reduction in body weight after IH exposure. IH had no impacts on elevated levels of serum lipids including LDL, HDL and total cholesterol in both HF groups of 6N and 6J mice, but significant reduction was observed in lean 6J mice after subjecting to IH. In addition, levels of serum free fatty acid (FFA) were also elevated in HF group of both strains without any IH impact. However, IH exposure significantly caused elevation of serum FFA level and IL-6 levels in subcutaneous and visceral adipose tissues of lean 6J but not lean 6N mice.
Conclusion: Our current data reveal that the genetic difference between 6N and 6J mice has direct impact on IH. The effect of HF diet may be more obvious in 6N mice while the 6J mice may be more sensitive to IH. Therefore, the impact of background substrain needs to be considered for designing the experimental IH-exposed mouse model.