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CLINICAL RESEARCH: ENDOTHELIAL FUNCTION AND VISCERAL FAT

Modest Visceral Fat Gain Causes Endothelial Dysfunction in Healthy Humans

Abel Romero-Corral, MD, MS^_*, Fatima H. Sert-Kuniyoshi, PhD^_*, Justo Sierra-Johnson, MD, PhD, Marek Orban, MD^_*, Apoor Gami, MD^_*, Diane Davison, RN^_*, Prachi Singh, PhD^_*, Snigdha Pusalavidyasagar, MD^_*, Christine Huyber^_*, Susanne Votruba, PhD, Francisco Lopez-Jimenez, MD, MSc^_*, Michael D. Jensen, MD and Virend K. Somers, MD, PhD^_*,_*

^_* Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota
Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota
Department of Medicine, Atherosclerosis Research Unit, Karolinska Institutet, Stockholm, Sweden

Manuscript received December 16, 2009; revised manuscript received February 22, 2010, accepted March 9, 2010.

^_* Reprint requests and correspondence: Dr. Virend K. Somers, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905 (Email: somers.virend{at}mayo.edu).

Objectives: The aim of this study was to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans.

Background: Endothelial dysfunction has been identified as an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown.

Methods: A randomized controlled study was conducted to assess the effects of fat gain on endothelial function. Forty-three normal-weight healthy volunteers were recruited (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n = 35) or to maintain weight (n = 8). Endothelial function (brachial artery flow-mediated dilation [FMD]) was measured at baseline, after fat gain (8 weeks), and after weight loss (16 weeks) for fat gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition was measured by dual-energy X-ray absorptiometry and abdominal computed tomographic scans.

Results: After an average weight gain of 4.1 kg, fat gainers significantly increased their total, visceral, and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight maintainers. FMD decreased in fat gainers (9.1 ± 3% vs. 7.8 ± 3.2%, p = 0.003) but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho = –0.42, p = 0.004), but not with subcutaneous fat gain (rho = –0.22, p = 0.15).

Conclusions: In normal-weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. (Fat Gain and Cardiovascular Disease Mechanisms; NCT00589498)

Key Words: weight gain • endothelial function • visceral fat

Abbreviations and Acronyms   BMI = body mass index   CRP = C-reactive protein   FMD = flow-mediated dilation

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