Negative Impact of Caloric Restriction on Atherosclerosis in Young ApoE/LDLr ^-/- Mice

Caloric restriction (CR) has proven to be the most effective dietary intervention for reducing cardiovascular disease (CVD) associated with obesity. Depending on the age of the mice the effect of caloric restriction was diverse. Therefore, the effect of CR on the development of atherosclerosis in young and adult ApoE/LDLr^-/- mice was evaluated.

Eight-week-old and 20-week-old male mice received a control diet. Young mice were fed for eight weeks, whereas adult mice for 5 weeks. To assess whether individual housing influenced the tested parameters, control animals were housed in colony cages (AL) or individually (stressAL; sAL) and fed ad libitum. Individually housed caloric restriction (CR) mice received a 30% less diet compared to AL group.

The body weight of CR mice was significantly lower compared to the AL and sAL groups. TCh and LDL levels were significantly increased in young CR mice. No differences in adult animals were observed. TAG levels significantly decreased in both young and adult CR mice. CR induced atherosclerosis in young mice. The FMO3 gene was upregulated in young animals. Microbiota composition changed. At the genus level, compared to the control, CR group exhibited a higher relative abundance of the Enterococcus, Clostridium_sensu_stricto_1 , Rikenella and a lower relative abundance of the CAG_352 (P< 0.05) genera.

Caloric restriction exacerbated atherosclerosis in young ApoE/LDLr^-/- mice.