Low-Fat Diet Designed for Weight Loss But Not Weight Maintenance Improves Nitric Oxide-Dependent Arteriolar Vasodilation in Obese Adults

Abstract

Obesity is associated with microvascular dysfunction. While low-fat diet improves cardiovascular risk, its contributions on microvascular function, independent of weight loss, is unknown. We tested the hypothesis that nitric oxide (NO)-dependent vasodilation in microvessels is improved by low-fat diets designed for weight loss (LFWL) compared to low-fat weight maintenance (LFWM) diet. Obese adults were randomly assigned to either a LFWL diet (n = 11) or LFWM diet (n = 10) for six weeks. Microvessels were obtained from gluteal subcutaneous fat biopsies before and after the intervention for vascular reactivity measurements to acetylcholine (Ach) and flow, with and without L-NAME or indomethacin. Vascular and serum NO and C-reactive protein (CRP) were also measured. LFWL diet increased flow-induced (FID) and ACh-induced dilation (AChID); an effect that was inhibited by L-NAME. Conversely, LFWM diet did not affect FID or AChID. Indomethacin improved FID and AChID in the baseline and this effect was minimized in response to both diets. Serum NO or CRP did not change in response to either diet. In conclusion, LFWL diet improves microvascular reactivity compared to LFWM diet and increased vascular NO contribution to the improved microvascular dilation. These data suggest that weight reduction on low fat diet is critical for microvascular health.

Keywords: acetylcholine; cardiovascular; flow-induced dilation; hypocaloric; isocaloric; low-fat diet; microvasculature; nitric oxide; obesity; weight loss.

Figure 1

Study flow chart.

Figure 2

Percent vasodilation in isolated adipose tissue arterioles at 0 (pre) and 6 weeks (post) from WL or WM diet. FID measurements corresponding to increasing intraluminal pressure gradients of 10–100 cmH₂O (A and B). AchID measurements corresponding to increasing concentrations of Ach (10⁻⁹ to 10⁻⁴ M) (C and D). All measurements are presented as means ± SE. * (p < 0.05) for comparing the pre- vs. post-intervention states.

Figure 3

Effects of LNAME on arteriolar FID and AchID at the pre- and post-WL-intervention states. FID measurements corresponding to increasing intraluminal pressure gradients of 10–100 cmH₂O in the presence or absence of LNAME (10⁻⁴ M) (A and B). AchID measurements corresponding to increasing concentrations of Ach (10⁻⁹ to 10⁻⁴ M) in the presence and absence of LNAME (10⁻⁴ M) (C and D). All measurements are presented as means ± SE. * (p < 0.05) for comparing baseline and LNAME in (A,B) and the pre- vs. post-intervention states in (C,D).

Figure 4

Percent vasodilation and absolute changes in arteriolar FID in response to indomethacin and LNAME at the pre- and post-WL-intervention states. FID measurements corresponding to increasing intraluminal pressure gradients of 10–100 cmH₂O in the presence and absence of indomethacin (10⁻⁵ M) (A and B). Absolute changes in FID were measured in response to LNAME (10⁻⁴ M) or indomethacin (10⁻⁵ M) incubation for 30 min (C and D). All measurements are presented as means ± SE. * (p < 0.05) for comparing baseline and indomethacin in (A,B) and the pre- vs. post-intervention states in (C,D).

Figure 5

Effects of LNAME on arteriolar FID and AchID at the pre- and post-WM-intervention states. FID measurements corresponding to increasing intraluminal pressure gradients of 10–100 cm H₂O in the presence or absence of LNAME (10⁻⁴ M) (A and B). AchID measurements corresponding to increasing concentrations of Ach (10⁻⁹ to 10⁻⁴ M) in the presence and absence of LNAME (10⁻⁴ M) (C and D). All measurements are presented as means ± SE. * (p < 0.05) for comparing baseline with LNAME.

Figure 6

Percent vasodilation and absolute changes in arteriolar FID in response to indomethacin and LNAME at the pre- and post-WM-intervention states. FID measurements corresponding to increasing intraluminal pressure gradients of 10–100 cmH₂O in the presence and absence of indomethacin (10⁻⁵ M) (A and B). Absolute changes in FID were measured in response to LNAME (10⁻⁴ M) or indomethacin (10⁻⁵ M) incubation for 30 min (C and D). All measurements are presented as means ± SE. * (p < 0.05) for comparing baseline and indomethacin in (A,B) and the pre- vs. post-intervention states in (C,D).

Figure 7

NO production in isolated adipose tissue arterioles. (A) Representative fluorescence microscopy images of NO generation conditions and after LNAME incubation (10⁻⁴ M) for 30 min. (B) NO fluorescent signals were measured and expressed in arbitrary units using NIH Image J software. (C) Absolute changes in arteriolar NO fluorescence after LNAME (10⁻⁴ M) incubation in post-WL and post-WM groups relative to pre-diet NO measurements. All measures are represented as means ± SE. * (p < 0.05) for comparing baseline with LNAME in (B) and the pre- vs. post-intervention states in (C).

Figure 8

Serum NO (nitrate/nitrite) (A) and CRP levels (B) at the pre- and post- WL and WM intervention states. All measures represent the means ± SE.