Modest Gain In Visceral Fat Causes Dysfunction Of Blood Vessel Lining In Lean, Healthy Humans

Significance of the Study

The study is the first randomized, blinded, controlled trial to assess the effects of weight gain -- and subsequent weight loss -- on endothelial function. Endothelial cells line the blood vessels. When not functioning correctly, they impede blood flow, which can predispose a person to heart attack or stroke. Determining how modest weight gain affects the condition was important due to the growing number of overweight adults worldwide.

"The effects of obesity on heart health receives a lot of attention, but less scrutiny has been given to the impact on the endothelium of modest weight gain in otherwise healthy people," says Virend Somers, M.D., Ph.D., Mayo Clinic cardiologist and senior author. "In fact, many adults accept this kind of weight gain -- 9 or 10 pounds -- as just part of aging. The assumption has generally been that a modest rise in body fat was more an issue of going up a clothing size, not a health issue. This study suggests otherwise, providing evidence that may help change our cultural attitude to the implications of modest weight gain as we age -- and perhaps strengthen the argument for diet and exercise to control weight as a means of protecting against cardiovascular disease."

The study's first author, Abel Romero Corral, M.D., of Mayo Clinic, says, "There are three parts to the take-home message here: One is that in healthy people, modest weight gain results in impaired endothelial function -- even in the absence of changes in blood pressure. The second is the encouraging news: endothelial function recovers after weight loss. The third point is that it is visceral fat -- the abdominal fat that surrounds internal organs -- rather than fat deposited as subcutaneous fat, just under the skin, that predicts endothelial dysfunction."

About the Study

The researchers recruited 43 lean, healthy volunteers from the community who each had a body mass index -- a statistical measure of the relationship of height to weight -- of between 18.5 and 24.9 kilograms of weight/meter2 of height. The average age was 29, and 42 percent were women. None took medications or smoked. After a weight maintenance period supervised by an experienced dietitian, volunteers randomly were assigned to either gain weight (4 kilograms [kg], or about 9 pounds) or maintain weight. The "fat-gainers" consisted of 35 people. The "weight-maintainer" group totaled eight.

Researchers used ultrasound to measure endothelial function of the large vessel in the upper arm called the brachial artery, under several flow conditions, always at the same time in the early morning. Low flow indicated vessel dysfunction. For the fat-gainers, endothelial function was measured at the start of the study, after fat gain at eight weeks and after weight loss at 16 weeks. For the weight maintainers, endothelial function was measured at the start of the study and at follow-up eight weeks later. To measure body fat percent, the researchers used advanced body composition analysis techniques, including abdominal CT scans.

Results

At the conclusion of the study:

• The fat-gainer group put on an average of 4 kg of fat and significantly increased their visceral and subcutaneous fat.
• In the weight-maintainer group, the two kinds of flow measurements taken in the brachial artery of the upper arm to assess endothelial dysfunction remained unchanged.
• In fat-gainers, brachial artery flow measurements decreased with the addition of weight. But once subjects shed the gained weight their flow levels improved, and returned to levels measured at the beginning of the study.
• Visceral fat gain -- but not subcutaneous fat gain -- was significantly correlated with the decreased flow conditions in the brachial artery.

The Mayo Clinic team presented the findings at the American Heart Association's Scientific Sessions 2007.

Other members of the Mayo Clinic research team included: Justo Sierra Johnson, M.D.; Marek Orban, M.D.; Apoor Gami, M.D.; Fatima Sert Kuniyoshi; Snigdha Pusalavidyasagar, M.B.B.S.; Diane Davison; Christine Huyber; Susanne Votruba; and Michael Jensen, M.D. This study was supported by a grant from the National Institutes of Health.