the effects of acylation stimulating protein supplementation vs antibody neutralization on energy expenditure in wildtype mice酰化的影响刺激补充蛋白质和抗体中和在野生型小鼠能量消耗.pdf

Paglialunga et al. BMC Physiology 2010, 10:4 /1472-6793/10/4 R E S E A R C H A R T I C L E Open Access Research article The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice 1,2 1 1 1,3 1 Sabina Paglialunga , Alexandre Fisette , Mercedes Munkonda , Ying Gao , Denis Richard and Katherine Cianflone*1,2 Abstract Background: Acylation stimulating protein (ASP) is an adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes. Previous studies have shown that ASP-deficient C3 knockout mice are hyperphagic yet lean, as they display increased oxygen consumption and fatty acid oxidation compared to wildtype mice. In the present study, antibodies against ASP (Anti-ASP) and human recombinant ASP (rASP) were tested in vitro and in vivo. Continuous administration for 4 weeks via osmotic mini-pump of Anti-ASP or rASP was evaluated in wildtype mice on a high-fat diet (HFD) to examine their effects on body weight, food intake and energy expenditure. Results: In mature murine adipocytes, rASP significantly stimulated fatty acid uptake (+243% vs PBS, P 0.05) while Anti-ASP neutralized the rASP response. Mice treated with Anti-ASP showed elevated energy expenditure (P 0.0001), increased skeletal muscle glucose oxidation (+141%, P 0.001), reduced liver glycogen (-34%, P 0.05) and glucose-6- phosphate content (-64%, P = 0.08) compared to control mice. There was no change in body weight, food intake, fasting insulin, adiponectin, CRP or TG levels compared to controls. Interestingly, HFD mice treated with rASP showed the opposite phenotype with reduced energy expenditure (P 0.0001) and increased body