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


CONCLUSIONS
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.
Paglialunga
Sabina
S
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, G1V 4G5, Canada.
Fisette
Alexandre
A
Munkonda
Mercedes
M
Gao
Ying
Y
Richard
Denis
D
Cianflone
Katherine
K
D041721:3T3-L1 Cells; D000215:Acylation / Q000502:physiology; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002153:Calorimetry, Indirect; D003176:Complement C3; D004041:Dietary Fats / Q000493:pharmacokinetics; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000493:pharmacokinetics; D006728:Hormones / Q000097:blood; D006801:Humans; D007260:Infusion Pumps; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000494:pharmacology
D057134:Antibodies, Neutralizing; D001786:Blood Glucose; C545610:C3 protein, mouse; D003176:Complement C3; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins