Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin

被引:127
作者
Van Hermelen, V
Reynisdottir, S
Cianflone, K
Degerman, E
Hoffstedt, J
Nilsell, K
Sniderman, A
Arner, P
机构
[1] Huddinge Univ Hosp, MK Div, Ctr Metab & Endocrinol, Karolinska Inst,Dept Med, S-14186 Huddinge, Sweden
[2] Huddinge Univ Hosp, Karolinska Inst, Res Ctr, Dept Surg, S-14186 Huddinge, Sweden
[3] McGill Univ, Royal Victoria Hosp, Mike Rosenbloom Lab Cardiovasc Res, Montreal, PQ H3A 1A1, Canada
[4] Lund Univ, Dept Cell & Mol Biol, Sect Mol Signalling, S-22100 Lund, Sweden
关键词
D O I
10.1074/jbc.274.26.18243
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effects of acylation-stimulating protein (ASP) and insulin on free fatty acid (FFA) release from isolated human fat cells and the signal transduction pathways to induce these effects were studied. ASP and insulin inhibited basal and norepinephrine-induced FFA release by stimulating fractional FFA re-esterification (both to the same extent) and by inhibiting FFA produced during lipolysis (ASP to a lesser extent than insulin). Protein kinase C inhibition influenced none of the effects of ASP or insulin. Phosphatidylinositol S-kinase inhibition counteracted the effects of insulin but not of ASP. Phosphodiesterase 3 (PDE3) activity was stimulated by ASP and insulin, whereas PDE4 activity was slightly increased by ASP only. Selective PDES inhibition reversed the effects of both ASP and insulin on fractional FFA re-esterification and lipolysis. Selective PDE4 inhibition slightly counteracted the ASP but not the effect of insulin on fractional FFA re-esterification and did not prevent the action of ASP or insulin on lipolysis. Thus, ASP and insulin play a major role in regulating FFA release from fat cells as follows: insulin by stimulating fractional FFA re-esterification and inhibiting lipolysis and ASP mainly by stimulating fractional FFA re-esterification. For both ASP and insulin these effects on FFA release are mediated by PDES, and for ASP PDE4 might also be involved. The signaling pathway preceding PDE is not known for ASP but involves phosphatidylinositol 3-kinase for insulin.
引用
收藏
页码:18243 / 18251
页数:9
相关论文
共 53 条
[1]  
ARNER P, 1991, INT J OBESITY, V15, P327
[2]   MONO-CYLGLYCEROLS AND DIACYLGLYCEROLS IN HUMAN ADIPOSE-TISSUE [J].
ARNER, P ;
OSTMAN, J .
BIOCHIMICA ET BIOPHYSICA ACTA, 1974, 369 (02) :209-221
[3]  
ARNER P, 1995, INT J OBESITY, V19, P435
[4]   THE ADIPSIN ACYLATION STIMULATING PROTEIN SYSTEM AND REGULATION OF INTRACELLULAR TRIGLYCERIDE SYNTHESIS [J].
BALDO, A ;
SNIDERMAN, AD ;
STLUCE, S ;
AVRAMOGLU, RK ;
MASLOWSKA, M ;
HOANG, B ;
MONGE, JC ;
BELL, A ;
MULAY, S ;
CIANFLONE, K .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (03) :1543-1547
[5]  
BALDO A, 1995, J LIPID RES, V36, P1415
[6]   EFFECTS OF INSULIN ON FATTY-ACID REESTERIFICATION IN HEALTHY-SUBJECTS [J].
BODEN, G ;
CHEN, XH ;
DESANTIS, RA ;
KENDRICK, Z .
DIABETES, 1993, 42 (11) :1588-1593
[7]   EFFECTS OF HORMONES ON THE RATE OF THE TRIACYLGLYCEROL FATTY-ACID SUBSTRATE CYCLE IN ADIPOCYTES AND EPIDIDYMAL FAT PADS [J].
BROOKS, B ;
ARCH, JRS ;
NEWSHOLME, EA .
FEBS LETTERS, 1982, 146 (02) :327-330
[8]   FAT-METABOLISM IN HUMAN OBESITY [J].
CAMPBELL, PJ ;
CARLSON, MG ;
NURJHAN, N .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (04) :E600-E605
[9]  
CAMPBELL PJ, 1992, AM J PHYSIOL, V263, pE1063
[10]   The acylation stimulating protein pathway: Clinical implications [J].
Cianflone, K .
CLINICAL BIOCHEMISTRY, 1997, 30 (04) :301-312