Dietary restriction slightly affects glucose homeostasis and delays plasma cholesterol removal in rabbits with dietary lipid lowering

Dietary restriction (DR) has been reported to have beneficial effects on atherosclerotic progression as well as lipid and glucose metabolism, but little is known about whether these effects can be enhanced or weakened by dietary lipid lowering. Here, after 12 weeks of high-cholesterol diet feeding, hypercholesterolemic rabbits were fed with either a standard chow diet ad libitum (AL) or a standard chow diet with DR for 16 weeks of dietary lipid lowering. We found that the DR group exhibited a loss of body weight, smaller internal organs, and reduced fat mass, while the AL group accumulated more subcutaneous fat than the baseline group. DR treatment slightly worsened glucose tolerance but enhanced insulin sensitivity, and a slight effect of DR on insulin secretion was also observed. After dietary cholesterol withdrawal, rabbits showed persistent lowering of total cholesterol and triglycerides in plasma. However, the DR group had significantly higher plasma total cholesterol than the AL group at most time points during weeks 7 to 16 of lipid lowering. Although both the AL and DR groups developed more severe atherosclerosis than the baseline group, DR did not improve atherosclerotic progression or the accumulation of macrophages and smooth muscle cells. We conclude that DR affected glucose and lipid metabolism but did not ameliorate atherosclerosis in rabbits when associated with lipid lowering by dietary cholesterol withdrawal.