Inflammation associated weight cycling contributes to an obesogenic memory phenotype in adipose tissue

Abstract

Energy expenditure through physical activity and dieting promotes weight loss. However, sustaining a healthy weight can be challenging and often a pattern known as weight cycling emerges. We evaluated the inflammatory status of mice undergoing weight cycling. Male C57BL/6 mice were randomized into four groups (n=10/group): low fat diet (LFD) for 32 weeks (LFD), high fat diet (HFD) for 32 weeks (HFD), LFD for 28 weeks then changed to HFD for 4 weeks (LFD->H), HFD for 21 weeks then changed to LFD for 7 weeks and then changed to HFD for 4 weeks (HFD->L->H). LFD->H and HFD->L->H mice did not significantly differ in body weight, body fat weight, or body fat percentage, but were significantly higher than LFD mice while remaining lower than HFD mice (p<0.05). In addition, HFD->L->H mice had smaller adipocytes of the epididymal fat pad compared to HFD and LFD->H mice which both had larger adipocytes (p<0.05) compared to LFD. TNFα and IFNγ were higher (p<0.05) in the epididymal fat pad of HFD->L->H mice compared to LFD and LFD->H mice. This was consistent with more M1-type macrophages (p<0.05) and cytotoxic T-cells (p<0.05) as indicated by ITGAX and CD8a gene expression, respectively. However, MCP1 was significantly lower (p<0.05) in HFD->L->H mice compared to LFD->H. Liver histopathological and protein analysis revealed HFD->L->H mice had greater NASH and NAS (p<0.05) scores, increased total STAT3 and NF-kB (p<0.05) compared to LFD controls. Taken together, weight cycling can lead to aberrations in the storage of triglycerides when challenged with an increased caloric intake. This is further supported by an increase in adipose tissue inflammation in weight cycling mice which is likely contributing to the observed obesogenic memory phenotype.