HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/C1518    most recent 00368.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Suh, H. N. Articles by Han, H. J. Search for Related Content PubMed PubMed Citation Articles by Suh, H. N. Articles by Han, H. J.

RECEPTORS AND SIGNAL TRANSDUCTION

Linoleic acid stimulates gluconeogenesis via Ca²⁺/PLC, cPLA₂, and PPAR pathways through GPR40 in primary cultured chicken hepatocytes

¹Department of Veterinary Physiology, Biotherapy Human Resources Center (BK21), College of Veterinary Medicine, Chonnam National University, Gwangju, Korea; ²Department of Obstetrics and Gynecology, Chosun University Medical School, Gwangju, Korea; and ³Department of Veterinary Physiology, College of Veterinary Medicine, Seoul National University, Seoul, Korea

Submitted 15 July 2008 ; accepted in final form 1 October 2008

Fatty acids serve vital functions as sources of energy, building materials for cellular structures, and modulators of physiological responses. Therefore, this study examined the effect of linoleic acid on glucose production and its related signal pathways in primary cultured chicken hepatocytes. Linoleic acid (double-unsaturated, long chain) increased glucose production in a dose (10^–4 M)- and time (8 h)-dependent manner. Both oleic acid (monounsaturated, long chain) and palmitic acid (saturated, long chain) also increased glucose production, whereas caproic acid (saturated, short chain) failed to increase glucose production. Linoleic acid increased G protein-coupled receptor 40 (GPR40; also known as free fatty acid receptor-1) protein expression and glucose production that was blocked by GPR40-specific small interfering RNA. Linoleic acid increased intracellular calcium concentration, which was blocked by EGTA (extracellular calcium chelator)/BAPTA-AM (intracellular calcium chelator), U-73122 (phospholipase C inhibitor), nifedipine, or methoxyverapamil (L-type calcium channel blockers). Linoleic acid increased cytosolic phospholipase A₂ (cPLA₂) phosphorylation and the release of [³H]-labeled arachidonic acid. Moreover, linoleic acid increased the level of cyclooxygenase-2 (COX-2) protein expression, which stimulated the synthesis of prostaglandin E₂ (PGE₂). The increase in PGE₂ production subsequently stimulated peroxisome proliferator-activated receptor (PPAR) expression, and MK-886 (PPAR- antagonist) and GW-9662 (PPAR- antagonist) inhibited glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. In addition, linoleic acid-induced glucose production was blocked by inhibition of extracellular and intracellular calcium, cPLA₂, COX-2, or PPAR pathways. In conclusion, linoleic acid promoted glucose production via Ca²⁺/PLC, cPLA₂/COX-2, and PPAR pathways through GPR40 in primary cultured chicken hepatocytes.

phospholipase C; cytosolic phospholipase A₂ phospholipase A; cyclooxygenase-2; peroxisome proliferator-activated receptors; G protein-coupled receptor 40; free fatty acid; glucose; liver

This article has been cited by other articles:

				T. Alquier, M.-L. Peyot, M. G. Latour, M. Kebede, C. M. Sorensen, S. Gesta, C. Ronald Kahn, R. D. Smith, T. L. Jetton, T. O. Metz, et al. Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets Diabetes, November 1, 2009; 58(11): 2607 - 2615. [Abstract] [Full Text] [PDF]