Weight loss alone improves conduit and resistance artery endothelial function in young and older overweight/obese adults

Abstract

Obesity is associated with vascular endothelial dysfunction, as indicated by impaired endothelium-dependent dilation. Presently there is no direct evidence that energy intake-restricted weight loss alone improves conduit or resistance artery endothelium-dependent dilation, the mechanisms involved, or whether improvements differ with patient age. A total of 40 overweight or obese (body mass index: >or=25<40 kg/m(2)) nondiabetic men and women aged 21 to 69 years completed 12 weeks of reduced energy intake (n=26; 15 male) or attention control (n=14; 9 male) and 4 weeks of weight maintenance (randomized trial). Energy intake restriction reduced estimated total energy intake (33%), body weight (10.5%), total and abdominal body fat, plasma leptin, oxidized low-density lipoprotein, and improved several metabolic risk factors. Brachial artery flow-mediated dilation was increased by 30% (6.0+/-0.7% versus 7.9+/-0.7%Delta; P=0.01; n=17). Peak forearm blood flow during intrabrachial artery infusion of acetylcholine was increased by 26% (16.8+/-1.4 versus 21.1+/-1.9 mL/100 mL per minute; P<0.05; n=15); this was inversely related to the reduction in the abdominal visceral:subcutaneous fat ratio (r=-0.46; P<0.05) and was abolished by inhibition of NO synthesis with N(G)-monomethyl-L-arginine. Improvements in endothelium-dependent dilation were not related to age: mean increases in subjects >50 years of age were similar to or greater than those <50 years of age. Energy intake-restricted weight loss alone is an effective intervention for improving peripheral conduit and resistance artery endothelial function in young and older overweight/obese adults. The improvements in resistance artery function are mediated by an increase in NO bioavailability and are related to reductions in abdominal visceral fat.

Figure 1

Endothelium-dependent dilation (brachial artery flow mediated dilation, FMD; percentage change [Δ%], absolute change [Δ mm]) (top) at baseline and after treatment (16 weeks) in the weight loss (n=17) and attention control (n=11) groups and endothelium-independent dilation (brachial artery dilation in response to sublingual nitroglycerin, NTG) (bottom) at baseline and after 16 weeks of treatment in the weight loss (n=11) or attention control (n=7) groups. Values are mean ± SE. *P<0.05 vs. baseline; †P<0.05 group (weight loss, attention control) × time (baseline, 16 weeks) interaction.

Figure 2

Relation between changes (Δ) in brachial artery flow-mediated dilation (FMD) and plasma norepinephrine concentrations in response to weight loss (n=16).

Figure 3

Endothelium-dependent dilation (during control acetylcholine and inhibition of nitric oxide synthesis with N^g-monomethyl L-arginine [L-NMMA]) and endothelium-independent dilation (forearm blood flow responses to intra-brachial artery infusion of acetylcholine and sodium nitroprusside, respectively) at baseline and after weight loss (16 weeks; n=15). Values are mean ± SE. *P<0.05 vs. baseline; †P<0.05 dose × time interaction; FAV=forearm volume.

Figure 4

Relation between changes (Δ) in peak forearm blood flow (FBF) to acetylcholine and the abdominal visceral fat:abdominal subcutaneous fat (AVF/ASF) ratio in response to weight loss (n=15). FAV=forearm volume.