A 7-day high-PUFA diet reduces angiopoietin-like protein 3 and 8 responses and postprandial triglyceride levels in healthy females but not males: a randomized control trial

Abstract

Background: Polyunsaturated fatty acids (PUFAs) have beneficial effects on hypertriglyceridemia although their effect on angiopoietin-like proteins (ANGPTLs), specifically ANGPTL3, ANGPTL4 and ANGPTL8 is unknown.

Objective: To determine whether a high-PUFA diet improves postprandial triglyceride (TG) levels through reducing ANGPTL responses following high saturated fat (SFA) meals.

Methods: Twenty-six adults were randomized into a PUFA diet (n = 16) or a control diet group (n = 10). Participants completed a pre-diet visit (v1) where they were given two SFA-rich, high-fat meals. Blood draws were taken at fasting and every 2 h postprandially for a total of 8 h. After v1, participants completed a 7d diet of the same macronutrient proportions (50% carbohydrate, 35% fat, 15% protein) but with different fatty acid (FA) compositions (PUFA = 21% of total energy from PUFAs vs. Control = 7% of total energy from PUFA). All participants then completed the post-diet visit (v2) identical to v1.

Results: In the PUFA group, females, but not males, reduced TG concentrations (Area under the curve (AUC): 141.2 ± 18.7 vs. 80.7 ± 6.5 mg/dL/h, p = 0.01, for v1 vs. v2, respectively). Fasting and postprandial AUC levels of ANGPTL3 and 8, but not ANGPTL4, also decreased from v1 to v2 in PUFA females, but not males. No changes from v1 to v2 were seen in either sex in the control group.

Conclusions: A PUFA-rich diet improves TG levels in response to high-SFA meals with reductions in ANGPTL3 and ANGPTL8. PUFAs may be more protective against hypertriglyceridemia in females, compared to males since no diet effect was observed in males.

Trial registration: NCT02246933.

Keywords: ANGPTL3; ANGPTL4; ANGPTL8; Angiopoietin-like proteins; High fat; Polyunsaturated fatty acid; Saturated fatty acid; Triglyceride.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

© The Author(s). 2019.

Figures

Fig. 1

Plasma TG response to SFA-rich meals before and after the PUFA diet. Changes in plasma TG are presented in PUFA-diet female (a) (n = 8) and male (b) (n = 8) subjects, and control diet female (c) (n = 5) and male (D) (n = 5) subjects before (dashed line) and after (solid line) the diets. In PUFA-diet females only, plasma TG concentrations were significantly lower at 2, 4, and 6 h after the 7-day diet. These differences were not significant in PUFA males or either sexes in the control group; * indicates a significant decrease compared to pre-diet levels in females (p < 0.05)

Fig. 2

Plasma TG Area Under the Curve (AUC). Changes from fasting through 8 h post meals were assessed using AUC in females and males on PUFA-rich and control diets. The 8-h AUC indicated that the female PUFA-diet group reduced total TG response whereas the other 3 groups did not; * indicates a significant decrease compared to pre-diet levels in females (p < 0.05)

Fig. 3

Plasma ANGPTL3 response to SFA-rich meals before and after the PUFA diet. Changes in plasma ANGPTL3 are presented in PUFA-diet female (a) (n = 8) and male (b) (n = 8) subjects, and control diet female (c) (n = 5) and male (d) (n = 5) subjects before (dashed line) and after (solid line) the diets. In PUFA-diet females only, fasting ANGPTL3 values decreased from pre- to post-diet visit (p < 0.01), but not in PUFA males. There was no significant change seen from pre- to post-diet visit in either sexes in the control group; * indicates a significant decrease compared to pre-diet levels in females (p < 0.05)

Fig. 4

Postprandial ANGPTL3 Area Under the Curve (AUC). Changes from fasting through 8 h post meals were assessed using AUC in females and males on PUFA-rich and control diets. The 8-h AUC indicated that the female PUFA-diet group reduced total ANGPTL3 response whereas the other 3 groups did not; * indicates a significant decrease compared to pre-diet levels in females (p < 0.05)

Fig. 5

Plasma ANGPTL8 response to SFA-rich meals before and after the PUFA diet. Changes in plasma ANGPTL8 are presented in PUFA-diet female (a) (n = 8) and male (b) (n = 8) subjects, and control diet female (c) (n = 5) and male (d) (n = 5) subjects before (dashed line) and after (solid line) the diets. In PUFA-diet females only, fasting ANGPTL8 values decreased from pre- to post-diet visit (p < 0.05), but not in PUFA males. There was no significant change seen from pre- to post-diet visit in either sexes in the control group; * indicates a significant decrease compared to pre-diet levels in females (p < 0.05)

Fig. 6

Postprandial ANGPTL8 Area Under the Curve (AUC). Changes from fasting through 8 h post meals were assessed using AUC in females and males on PUFA-rich and control diets. The 8-h AUC indicated that the female PUFA-diet group reduced total ANGPTL8 response whereas the other 3 groups did not; * indicates a significant decrease compared to pre-diet levels in females (p < 0.05)

Fig. 7

Plasma ANGPTL4 response to SFA-rich meals before and after the PUFA diet. Changes in plasma ANGPTL4 are presented in PUFA-diet female (a) (n = 8) and male (b) (n = 8) subjects, and control diet female (c) (n = 5) and male (d) (n = 5) subjects before (dashed line) and after (solid line) the diets. There were no significant changes in ANGPTL4 from pre- to post-diet visit in either sexes or in either diet group

Fig. 8

Postprandial ANGPTL4 Area Under the Curve (AUC). Changes from fasting through 8 h post meals were assessed using AUC in females and males on PUFA-rich and control diets. There were no differences in 8-h AUC between diets among any of the four groups