Mice lacking two related fatty acid binding proteins (FABPs), aP2 and mal1, exhibited striking changes in their lipid profiles and strong resistance to diet-induced obesity, insulin resistance, type 2 diabetes, and fatty liver disease, report Gkhan Hotamisligil and his colleagues at the Harvard School of Public Health. Earlier studies examining each of the proteins in isolation had missed their systemic effects because the two FABPs tend to compensate for one another, he explained.
Mice deficient for both proteins gained less weight than normal mice when fed a high-fat diet due to an increase in energy expenditure and resulting 25 percent reduction in total body fat, they found. Mice lacking the FABPs also exhibited significant shifts in the distribution of fatty acids in fat, muscle, and liver.
Mutant animals on the high-fat diet had significantly lower blood glucose and insulin levels than normal mice on the same diet. Rising blood glucose and insulin concentrations in overweight animals are an indicator of obesity-induced insulin resistance and type 2 diabetes. Examination of livers from the mutant mice also revealed a striking reduction in the infiltration of fat, in comparison to the livers of normal mice.
The cascade of cellular effects the researchers observed in fat cells, as well as cells of the muscle and liver, point to a sophisticated network of regulatory factors--including some yet to be identified--that
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