Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults

Abstract

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: Ն25Ͻ40 kg/m 2 ) nondiabetic men and women aged 21 to 69 years completed 12 weeks of reduced energy intake (nϭ26; 15 male) or attention control (nϭ14; 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% (6.0Ϯ0.7% versus 7.9Ϯ0.7%⌬; Pϭ0.01; nϭ17). Peak forearm blood flow during intrabrachial artery infusion of acetylcholine was increased by 26% (16.8Ϯ1.4 versus 21.1Ϯ1.9 mL/100 mL per minute; PϽ0.05; nϭ15); this was inversely related to the reduction in the abdominal visceral:subcutaneous fat ratio (rϭϪ0.46; PϽ0.05) 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 Ͼ50 years of age were similar to or greater than those Ͻ50 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. Key Words: endothelium Ⅲ obesity Ⅲ intra-abdominal fat Ⅲ nitric oxide Ⅲ energy intake Ⅲ adipokines Ⅲ aging O besity is associated with increased risk of cardiovascular diseases (CVDs), believed attributable in part to vascular endothelial dysfunction, as indicated by impaired endothelium-dependent dilation (EDD). 1,2 Thus, interventions that improve EDD in overweight and obese adults may have important clinical implications for the prevention of CVD.As reviewed recently, 3 surgical treatment, short-term verylow calorie diets, and multicomponent lifestyle interventions that include aerobic exercise and weight loss generally lead to improvements in EDD, particularly in overweight/obese adults with comorbidities. However, presently there is no evidence that moderate energy intake restriction-based weight loss alone improves EDD in otherwise healthy overweight/obese adults, 3 and no randomized trial with a nonweight loss control has been conducted on this question. This is important in that many overweight or obese adults who have not yet developed other clinical disorders are not candidates for gastric-bypass surgery, cannot sustain diets involving severe caloric restriction, and/or will not exercise regularly.If energy intake restriction...

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

“…In obese non-diabetic subjects, improvement in brachial artery FMD following a 6-week low-fat weight loss diet, but not a high-fat weight loss diet, was associated with decreased visceral fat mass and an improved adipokine profile, specifically increased adiponectin and decreased leptin and resistin [89]. Improvement in resistance artery endothelial function following weight loss was mediated by increased NO bioavailability and associated with reductions in abdominal visceral fat [86]. In patients with CAD, greater weight reduction following exercise training was associated with a greater increase in FMD, suggesting a dose response effect [87].…”

“…In type 2 diabetic patients, a reduction in insulin resistance and fat mass following prolonged aerobic exercise resulted in improvements in lipoprotein metabolism [84]. Dietary restriction, weight loss, and increased physical activity have been shown to improve conduit and resistance artery ED in overweight and obese non-diabetic subjects with and without CAD [85][86][87][88]. In obese, but otherwise healthy subjects, brachial artery FMD improved with a 6-week lowfat diet but was blunted with a low-carbohydrate diet despite similar degrees of weight loss, suggesting that greater vascular benefit is conferred by a low-fat diet [85].…”

Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK–eNOS Pathway

“…A lot of evidences suggest endothelial dysfunction, an early pivotal event in the development, progression and manifestation of macroangiopathy, 1,2 is closely correlated with obesity 3,4 and plays a critical role in the development and onset of cardiovascular disease. 5 Numerous mechanisms have been proposed to explain this pathological alteration, 6,7,8 such as alteration of signaling mechanisms, alterations of nitric oxide synthase (NOS) expression and activity, and increased destruction of nitric oxide (NO) by superoxide, but the cross-talk between adipose tissue and endothelial dysfunction is still not quite clear.…”

Weight Loss and Vascular Function

“…4,5 Thus, it is reasonable to hypothesize that weight loss should be associated with an improvement in endothelial function and, thereby, a decrease in cardiovascular events. In the current issue of Hypertension, Pierce et al 6 report the results of testing the first part of this hypothesis. They describe the effect of weight loss on vascular function as measured by flow-mediated dilation in the forearm and changes in forearm blood flow in response to intraarterial infusions of acetylcholine, an endotheliumdependent vasodilator, as well as sodium nitroprusside, an endothelium-independent vasodilator.…”