Previously, we have shown that intervention by the addition of the citrus flavonoid naringenin to a chow diet enhances the reversal of diet-induced metabolic dysregulation, obesity, and atherosclerosis. However, the metabolic effects of naringenin in the absence of obesity and metabolic dysregulation are unknown. In the present study, we assessed the effect of naringenin supplementation to a chow diet on plasma lipids, adiposity, respiratory exchange ratio (RER), ambulatory activity and tissue lipolysis. For 8 weeks,
Ldlr
-/-
mice were fed an isoflavone-free chow diet supplemented with or without 3% naringenin. Over 8 weeks, there was no difference in caloric intake between the two groups. Naringenin supplementation reduced plasma VLDL-cholesterol (C) (-46%;
P
<0.05), VLDL-triglycerides (-43%;
P
<0.05), and LDL-C (-27%;
P
<0.05) compared to mice consuming chow alone. Chow-fed mice maintained body weight, whereas mice fed chow with naringenin were ~1.4 g lighter (
P
<0.05) with significantly reduced adiposity (-48%;
P
<0.05). Histological analysis of epididymal white adipose tissue showed naringenin supplementation reduced adipocyte size and number. Between 6 and 8 weeks of diet, mice were assessed in metabolic cages. Naringenin supplementation had no effect on food intake, ambulatory activity or energy expenditure during both the light and dark cycles. Consistently, naringenin-treated mice had significantly lower RER compared to mice fed chow alone (0.97 vs 0.99;
P
<0.05). This difference was driven by a significant suppression in RER during the light cycle (0.96 vs 1.00;
P
<0.05), but not the dark cycle (0.97 vs 0.98
N.S
), suggesting an enhanced starvation response. Triglyceride lipolysis was highest in white adipose tissue, followed by liver and muscle. Naringenin supplementation to chow increased the lipolytic rate in adipose, but not in muscle or liver, suggesting reduced adiposity was related to increased expression of ATGL or HSL. In conclusion, compared to chow alone, naringenin supplementation reduced plasma lipids and decreased body weight
via
increased adipose tissue lipolysis and suppressed RER, with no change in energy expenditure.
CD47 differentially regulates white and brown fat function