Acylation-stimulating protein/C5L2-neutralizing antibodies alter triglyceride metabolism in vitro and in vivo
| Autor: | HuiLing Lu, Wei Cui, Mathieu Laplante, Sabina Paglialunga, Katherine Cianflone, Yves Deshaies, David Kalant, Christian Roy |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Peptide Hormones CHO Cells Carbohydrate metabolism AMP-Activated Protein Kinases Fatty Acids Nonesterified Protein Serine-Threonine Kinases Antibodies Cell Line chemistry.chemical_compound Acylation stimulating protein Eating Mice Cricetulus AMP-activated protein kinase In vivo Multienzyme Complexes Physiology (medical) Internal medicine 3T3-L1 Cells Cricetinae medicine Adipocytes Animals Receptor Receptor Anaphylatoxin C5a Triglycerides biology Triglyceride Body Weight Glucose transporter Metabolism Lipid Metabolism Dietary Fats Mice Inbred C57BL Lipoprotein Lipase Endocrinology Glucose chemistry Biochemistry biology.protein Complement C3a Receptors Chemokine |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 293(6) |
| ISSN: | 0193-1849 |
| Popis: | Acylation-stimulating protein (ASP), a lipogenic hormone, stimulates triglyceride (TG) synthesis and glucose transport upon activation of C5L2, a G protein-coupled receptor. ASP-deficient mice have reduced adipose tissue mass due to increased energy expenditure despite increased food intake. The objective of this study was to evaluate the blocking of ASP-C5L2 interaction via neutralizing antibodies (anti-ASP and anti-C5L2-L1 against C5L2 extracellular loop 1). In vitro, anti-ASP and anti-C5L2-L1 blocked ASP binding to C5L2 and efficiently inhibited ASP stimulation of TG synthesis and glucose transport. In vivo, neither anti-ASP nor anti-C5L2-L1 altered body weight, adipose tissue mass, food intake, or hormone levels (insulin, leptin, and adiponectin), but they did induce a significant delay in TG clearance [ P < 0.0001, 2-way repeated-measures (RM) ANOVA] and NEFA clearance ( P < 0.0001, 2-way RM ANOVA) after a fat load. After treatment with either anti-ASP or anti-C5L2-L1 antibody there was no change in adipose tissue AMPK activity, but neutralizing antibodies decreased perirenal TG mass (−38.4% anti-ASP, −18.8% anti-C5L2, P < 0.01–0.001) and perirenal LPL activity (−75.6% anti-ASP, −72.5% anti-C5L2, P < 0.05). In liver, anti-C5L2-L1 decreased TG mass (−42.8%, P < 0.05), whereas anti-ASP increased AMPK activity (+34.6%, P < 0.001). In the muscle, anti-C5L2-L1 significantly increased TG mass (+128.0%, P < 0.05), LPL activity (+226.1%, P < 0.001), and AMPK activity (+71.1%, P < 0.01). In addition, anti-ASP increased LPL activity (+164.4, P < 0.05) and AMPK activity (+53.9%, P < 0.05) in muscle. ASP/C5L2-neutralizing antibodies effectively block ASP-C5L2 interaction, altering lipid distribution and energy utilization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|