Acylation stimulating protein and triacylglycerol synthesis: potential drug targets?
Triacylglycerol storage in adipose tissue is mediated by a host of transporters, enzymes and binding proteins. Additionally, several hormones (both autocrine and endocrine) are known to interact with cell surface receptors and modulate triacylglycerol synthesis (such as acylation stimulating protein, ASP). The many proteins involved contribute to the robustness of the system and, in most cases, deletion of a single gene is not deleterious and adipose tissue is preserved. On the other hand, this does not mean that gene disruption is not without effect, and in fact often results in a leaner, and presumably "healthier" mouse. These insights provide valuable indications for potential drug tools to delay and/or reverse obesity. In this review we examine the potential of ASP as a candidate target. ASP deficiency in mice decreases adipose tissue mass, increases insulin sensitivity and energy expenditure even in obese ob/ob mice, suggesting that partial interference of ASP action could be advantageous. ASP interacts with a specific cell surface receptor present in adipose tissue and certain structural components, such as the tightly folded core region, are implicated in activity. We propose that interference of the ASP-receptor interaction using an antagonist offers future prospect for an anti-obesity target.
Cianflone
K
K
McGill Unit for the Prevention of Cardiovascular Disease, McGill University Health Centre, Montreal, Quebec, Canada. katherine.cianflone@mcgill.ca
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001798:Blood Proteins / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D015926:Complement C3a / Q000031:analogs & derivatives*; D004734:Energy Metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis*
D001798:Blood Proteins; D007328:Insulin; D011956:Receptors, Cell Surface; D014280:Triglycerides; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a