Acylation stimulating protein (ASP) is a potent stimulator of triglyceride synthesis in adipocytes. In the present study, we have examined the effect of an ASP functional knockout (ASP(-/-)) on lipid metabolism in male mice. In both young (14 weeks) and older (26 weeks) mice there were marked delays in postprandial triglyceride clearance (80% increase at 14 weeks and 120% increase at 26 weeks versus wild type (+/+)). Postprandial nonesterified fatty acids were also increased in ASP(-/-) mice versus ASP(+/+) mice by 37% (low fat 10% Kcal) and by 73% (high fat 40% Kcal) diets, although there were no differences in fasting lipid levels. The ASP(-/-) mice had moderately increased energy intake (16% ± 2%p < 0.0001) and reduced feed efficiency (33% increase in calories/g of body weight gained on low fat diet) versus wild type. The ASP(-/-) mice also had modest changes in insulin/glucose metabolism (30% to 40% decrease in insulin·glucose product), implying increased insulin sensitivity. As well, there were decreases in leptin (29% shift in leptin to body weight ratio) and up to a 26% decrease in specific adipose tissue depots versus the wild type mice on both low fat and high fat diets. These results demonstrate that ASP plays an important role in adipose tissue metabolism and fat partitioning.
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