Changing the dietary composition improves inflammation but not adipocyte thermogenesis in diet-induced obese mice

Pronounced weight loss was shown to improve adipocyte dysfunction and insulin sensitivity in obese subjects. While bariatric surgery is frequently accompanied by adverse side effects, weight loss due to caloric restriction is often followed by weight regain. Here we aimed to determine whether switching the diet from a metabolically harmful Western type diet to a balanced standard diet is sufficient to reverse adipocyte dysfunction in diet-induced obese mice. Male C57BL/6 mice were fed a Western diet for 10 weeks and afterwards switched to a standard diet for eight more weeks (WD/SD mice) or continued to be fed a Western diet (WD/WD mice) ad libitum. Mice fed SD for 18 weeks served as control group (SD/SD). Insulin sensitivity was similar in WD/SD and SD/SD mice despite increased body weight in WD/SD mice. Beiging markers Ucp-1, Cidea and Cox8b were drastically reduced in subcutaneous adipose tissue of WD/SD mice when compared with SD/SD mice. Also, in brown adipose tissue morphologic features and markers of thermogenesis were still altered in both WD/SD and WD/WD mice. However, adipocyte size, Hif1α and macrophage infiltration were significantly lower in both, brown and white adipose tissues of WD/SD compared to WD/WD mice and additionally, a shift toward anti-inflammatory M2 phenotype was found in WD/SD mice only. In conclusion our data suggest that switching the diet is sufficient to improve adipose tissue inflammation, while western diet negatively affects thermogenic capacity of brown adipose tissue, and inhibits beiging of white adipose tissue in the long-term.