Story ideas from the Journal of Lipi...( Stories appearing in the Dec. 2007 J...)

Stories appearing in the Dec. 2007 Journal of Lipid Research (Vol. 48, No. 12)

• Genetic Variants Affect Diet-Associated Cholesterol Metabolism
• Crohns Disease Increases Progression of Atherosclerosis
• Breaking the Vicious Cycle of Bile Acid Disorders

Genetic Variants Affect Weight-Associated Cholesterol Metabolism

Researchers have found that variants in two metabolic genes alter how the body adjusts cholesterol metabolism in response to weight loss, a finding that may lead to screening tools to identify the optimal method of reducing cholesterol levels in specific individuals.

Dietary intake clearly contributes to elevated cholesterol levels. However, inherited factors such as mutations in proteins that regulate how much dietary cholesterol is absorbed, specifically ABCG5 and ABCG8, also influence the effect of diet on cholesterol trafficking. Several variants of ABCG5 and ABCG8 exist in the general population, each with different metabolic properties.

To study how these variants affect cholesterol metabolism in response to changes in weight loss from diet and exercise, Peter Jones and colleagues performed a before and after analysis of 35 women with elevated cholesterol who lost an average of 25 pounds over 20 weeks. They found two variants that were linked to significant changes in cholesterol metabolism. People with the 604E variant of ABCG5 experienced far larger decreases in cholesterol absorption and consequently had increased cholesterol synthesis after weight loss, while individuals with a 54Y variant of ABCG8 exhibited lower post-weight loss cholesterol synthesis.

The researchers believe these results can lead to better therapy for overweight individuals. Knowing which variants are present will increase the understanding of how weight loss will affect cholesterol metabolism, and the best combination of diet, exercise, and medicine can be prescribed.