ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P527

Regulation of acylation stimulating protein by insulin in overweight and obese postmenopausal women: a MONET study

David H St-Pierre1,4, Katherine Cianflone2,4, Jessica Smith2,4, Huiling Lu2,4, Lise Coderre1,4, Antony D Karelis3,4, Pascal Imbeault1,4, Jean-Marc Lavoie1,4 & Rémi Rabasa-Lhoret1,4

1Université de montréal, Montréal, Québec, Canada; 2Université Laval, Québec, Canada; 3Université du Québec à Montréal, Montréal, Québec, Canada; 4University of Ottawa, Ottawa, Ontario, Canada.

Objective: Acylation Simulating Protein (ASP) has been shown to regulate lipid clearance and glucose uptake in adipose tissue. In vitro studies demonstrate that insulin stimulates ASP secretion from adipocytes. Individuals with obesity and/or metabolic disturbances (insulin resistance and type 2 diabetes) have increased plasma ASP, suggesting ASP resistance. Therefore, the present study evaluates whether ASP levels are influenced by the metabolic profile of overweight and obese postmenopausal women during a euglycemic/hyperinsulinemic clamp (EHC).

Materials and methods: The study population consisted of 76 overweight and obese sedentary postmenopausal women. We evaluated insulin sensitivity using the EHC, ASP levels, body composition (fat mass and visceral adipose tissue area), blood lipid profile, liver enzymes, maximal aerobic capacity (VO2peak), resting metabolic rate and total energy expenditure using doubly labeled water.

Results: We observed wide inter-individual variations of ASP levels during the EHC. Therefore, subjects were divided into two groups based on a >20% change in ASP levels. Negative ASP Responders (NAR; n=24) showed, at least, a −20% decrease in ASP levels while Positive ASP Responders (PAR; n=42) displayed hormonal fluctuations superior to +20%. Ten subjects had an ASP change of less then 20% and were excluded from the analysis. PAR women displayed a worse metabolic profile then NAR women: higher BMI, visceral adipose tissue, fasting insulin levels, lean body mass, and alanine aminotransferase (ALT), a marker of impaired liver function. After adjustment for BMI, only ALT remained significantly different while lean body mass (P=0.08) and visceral adipose tissue (P=0.07) remained marginally higher. In PAR and NAR subjects, fasting ASP levels correlated positively with albumin and VO2peak and this association remained significant after adjustments for the effect of BMI. In addition, the % maximal change in ASP levels during the EHC was positively associated with aspartic acid aminotransferase (AST) and ALT.

Conclusion: Overall these results suggest that an elevated ASP response during the EHC is associated with metabolic disturbances in overweight and obese postmenopausal women.