NIH Research Matters
July 23, 2007
Blood Protein Warns of Hidden Belly Fat and Disease Risk
People with excess deep- belly fat are known to be at increased risk for cardiovascular disease and type 2 diabetes. Now scientists have found that this type of fat, compared to other types, produces higher levels of a protein that can be detected in the blood. The protein may serve as a simple indicator for deep visceral fat and disease risk.
In recent years scientists at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston have been exploring the unexpected complexity of the molecule retinol-binding protein (RBP4), once thought to have the sole purpose of ferrying vitamin A (retinol) through the bloodstream. The researchers, led by Dr. Barbara B. Kahn, showed that it appears to affect insulin resistance, a risk factor for diabetes, in mice. In people, RBP4 is elevated in obese or diabetic individuals with insulin resistance, and it drops with exercise training or other interventions known to reverse insulin resistance.
In the new study, reported in the July 2007 issue of the journal Cell Metabolism, the scientists set out to determine if blood levels of RBP4 were directly influenced by visceral fat, which surrounds abdominal organs and has been linked to disease risk. They measured blood levels of RBP4 in 130 obese and 66 lean people. Each participant underwent a computed tomography (CT) scan to assess relative amounts of visceral fat and subcutaneous fat, which lies just beneath the skin. The researchers also analyzed RBP4 gene expression in small samples of both visceral and subcutaneous fat from each person. The study was funded in part by NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
The scientists found that, overall, RBP4 gene expression was 5-fold higher in visceral than in subcutaneous fat. In obese people with a "visceral fat" pattern of obesity, RBP4 gene expression in visceral fat cells was 60-fold higher than in the lean group. By comparison, RBP4 expression increased just 12-fold in people with a "subcutaneous fat" pattern.
Blood levels of RBP4 measured up to 3 times higher in obese than in lean people. Those with higher blood levels of RBP4 had a corresponding increase in abdominal fat and a reduction in insulin sensitivity, regardless of their age, gender or body mass index (a ratio of weight to height).
Among several fat-secreted proteins now associated with insulin activity, blood concentration of RBP4 is thus far the strongest predictor of a person's visceral fat load and insulin resistance. With further study, RBP4 may serve as a convenient marker to identify patients at risk for type 2 diabetes and cardiovascular disease.—by Vicki Contie
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Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.
NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.