Maternal high-fat diet impacts endothelial function in nonhuman primate offspring

Abstract

Objective: The link between maternal under-nutrition and cardiovascular disease (CVD) in the offspring later in life is well recognized, but the impact of maternal over-nutrition on the offspring's cardiovascular function and subsequent risk for CVD later in life remains unclear. Here, we investigated the impact of maternal exposure to a high-fat/calorie diet (HFD) during pregnancy and early postnatal period on endothelial function of the offspring in a nonhuman primate model.

Methods: Offspring, naturally born to either a control (CTR) diet (14% fat calories) or a HFD (36% fat calories) consumption dam, were breast-fed until weaning at about 8 months of age. After weaning, the offspring were either maintained on the same diet (CTR/CTR, HFD/HFD), or underwent a diet switch (CTR/HFD, HFD/CTR). Blood samples and arterial tissues were collected at necropsy when the animals were about 13 months of age.

Results: HFD/HFD juveniles displayed an increased plasma insulin level and glucose-stimulated insulin secretion in comparison with CTR/CTR. In abdominal aorta, but not the renal artery, acetylcholine-induced vasorelaxation was decreased remarkably for HFD/HFD juveniles compared with CTR/CTR. HFD/HFD animals also showed a thicker intima wall and an abnormal vascular-morphology, concurrent with elevated expression levels of several markers related to vascular inflammation and fibrinolytic function. Diet-switching animals (HFD/CTR and CTR/HFD) displayed modest damage on the abdominal vessel.

Conclusion: Our data indicate that maternal HFD exposure impairs offspring's endothelial function. Both early programming events and postweaning diet contribute to the abnormalities that could be reversed partially by diet intervention.

Figure 1

ACh-induced endothelium-dependent vasorelaxation response in abdominal aorta tissue. (a) Cumulative concentration-relaxation (%) curves for ACh (−10 to −5.5 LogM) in abdominal aorta rings against U₄₆₆₁₉ (9,11-dideoxy-11α, 9α-epoxy-methanoprostaglandin F_2α). (b) Corresponding EC₅₀ value for each curve. (c) Correlative relationship between EC₅₀ and IAUC for juveniles born to HFD consumption dams. (d) Contracting forces against U₄₆₆₁₉. Values were expressed as mean±s.e., n=6–10. ^**P<0.01 vs C/C, ^ΔP<0.05 and ^ΔΔP<0.01 vs H/H.

Figure 2

Intima thickness of the abdominal aorta tissue. (a) Mean intima thickness value of abdominal aorta tissue for various groups of juvenile offspring. (b) Immunohistochemistry pictures immunostained with endothelial marker CD₃₁, typical showing the intima thickness for abdominal aorta taken from C/C and H/H animals. Arrows indicate areas of intima thickening, and the top boxes indicate areas of enlarged pictures. Values were expressed as mean±s.e., n=3–5. ^*P<0.05 and ^**P<0.01 vs C/C.

Figure 3

Morphological assessment of the abdominal aorta tissue. H&E staining pictures typically showing the different morphological manifestation for the abdominal aorta rings taken from animals from C/C and H/H. Top boxes indicate areas of enlarged pictures below.

Figure 4

Expression of proinflammatory factors in abdominal aorta tissue. (a) Relative expression levels of VEGF, TNFα and ICAM-1, in abdominal aorta tissue of Juvenile offspring. (b) Relative expression levels of IL-6, VCAM-1 and MCP-1 in abdominal aorta tissue of Juvenile offspring. Values were expressed as mean±s.e., n=6–17. ^*P<0.05 and ^**P<0.01 vs C/C.

Figure 5

Expression of fibrinolytic factors in abdominal aorta tissue. (a) Relative expression level of PAI-1 and (b) the ratio between t-PA and PAI-1 in abdominal aorta tissue of juvenile offspring. Values were expressed as mean±s.e., n=6–17. ^*P<0.05, ^**P<0.01 vs C/C and ^ΔP<0.05, ^ΔΔP<0.01 vs H/H.