Effects of fat-to-sugar ratio in excess dietary energy on lipid abnormalities: a 7-month prospective feeding study in adult cynomolgus monkeys

Abstract

Background: Excess energy intake contributes to metabolic disorders. However, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. Here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys.

Methods: Four groups of adult cynomolgus monkeys were fed regular chow plus emulsion with combinations of high sugar (HS) or low sugar (HS) and low fat (LF) or high fat (HF) for 7 months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and blood glucose were measured for all the four groups of animals during the experiment.

Results: Plasma levels of TC and LDL-C gradually increased in all 4 diets groups, with the highest increase found in the LSHF group compared to the other three groups (P = 0.0018 and P = 0.0005 respectively). HF induced increased fasting glucose (P = 0.0077) and HS induced higher TG (P = 0.0227) respectively. Intriguingly, HSHF led to dramatically smaller magnitude of increase in LDL-C and TC levels compared to LSHF, while such difference was absent between the LSLF and LSHF groups. Our findings thus indicate interactive effects of HS and HF on TC and LDL-C. In addition, HF exhibited stronger effects on lipid abnormalities than HS.

Conclusions: In the current study, our prospective feeding experiment in adult cynomolgus monkeys revealed effects of different fat-to-sugar ratios on diet-induced metabolic abnormalities. Furthermore, our findings suggest that not only excess dietary energy but also the balance of dietary fat-to-sugar ratio matters in diet-induced lipid abnormalities.

Keywords: Cynomolgus monkey; Fasting glucose; High-fat diet; High-sugar diet; Lipid abnormality.

Fig. 1

Mean changes in body weight, fasting glucose and lipid profiles among four groups with different ratio of excess fat and sugar throughout the 7-month intervention. The monkeys in the four groups were fed regular chow plus emulsion with different ratio of excess fat and sugar. Results are shown for body weight (a), fasting glucose (b), total cholesterol (TC) c), triglyceride (TG) (d), HDL-C (e), LDL-C (f). Data are based on mixed-model analysis of variance. The P value at the upper or lower left indicates the test of whether the change between baseline and intervention period (mean of every two months) differed significantly between cynomolgus monkeys assigned to four groups. The P values for the comparison between the LSLF group and the HSLF group are 0.733 for total cholesterol and 0.934 for LDL-C cholesterol. The P values for the comparison between the LSLF group and the LSHF group are 0.0001 for TC and 0.0001 for LDL. The P values for the comparison between the HS/LF group and the HSHF group are 0.898 for TC and 0.885 for LDL. The P values for the comparison between the LS/HF group and the HSHF group are 0.0001 for total cholesterol and 0.0001 for LDL-C cholesterol. *p < 0.05

Fig. 2

Forest plots showing excess sugar×fat interaction model estimates by five time points. ES stand for adjusted mean differences after analysis of linear mixed effects models adjusting body weight by time. Panel (a) shows mean differences of TC between HS and LS combined with HF or LF, Panel (b) shows mean differences of TC between HF and LF combined with HS or LS, Panel (c) shows mean differences of LDL-C between HS and LS combined with HF or LF, Panel (d) shows mean differences of LDL-C between HF and LF combined with HS or LS