The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice

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 weight (P < 0.05), cumulative food intake (P < 0.0001) and liver glycogen content (+59%, P < 0.05). Again, there was no change in circulating insulin, adiponectin, CRP or TG levels, however, plasma free fatty acids were reduced (-48%, P < 0.05).In vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake. In vivo, Anti-ASP treatment increased whole body energy utilization while rASP increased energy storage. Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.Acylation stimulating protein (ASP) is a circulating adipokine elevated in obesity, diabetes and cardiovascular disease [1] as well as other metabolic disorders with hyperlipidemia such as polycystic ovarian syndrome (PCOS) [2], hypothyroidism [3] and lipoprotein lipase (LPL) deficiency [4]. ASP influences fat storage by stimulating diacylglycerol acyltransferase (DGAT) activity, the rate limiting step in triglyceride (TG) synthesis [5], increasing glucose transporter GLUT4 translocation [6], indirectly stimulating LPL activity in adipose tissue [7], and inhibiting lipolysis [8]. These effects are mediated through the C5L2 receptor, a G protein-coupled receptor highly expressed in adipose tissue depots, skeletal muscle and liver [9,10].ASP (C3adesArg) is the cleavage product of complement C3 (reviewed in [1]);