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: R800053-JLR200v1 50/Supplement/S74    most recent 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nagle, C. A. Articles by Coleman, R. A. Search for Related Content PubMed PubMed Citation Articles by Nagle, C. A. Articles by Coleman, R. A. Related Collections Related Webpages Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, S74-S79, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Metabolism

Hepatic triacylglycerol accumulation and insulin resistance

Cynthia A. Nagle, Eric L. Klett and Rosalind A. Coleman¹

Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

This work was supported by National Institutes of Health Grants DK56598, DK59935, and DK56350.

Published, JLR Papers in Press, November 6, 2008.

¹ AGPAT8 and AGPAT6 are correctly termed GPAT3 and GPAT4, respectively.

² CGI-58, and endophilin both have AGPAT activity.

³ Several additional enzymes exhibit some DGAT activity, including MGAT2.

¹ To whom correspondence should be addressed. email: rcoleman{at}unc.edu

ABSTRACT

The association of hepatic steatosis with hepatic insulin resistance and type 2 diabetes has prompted investigators to elucidate the underlying mechanism. In this review we focus on pathways of lipid metabolism, and we review recent data, primarily from mouse models, that link lipid intermediates with insulin resistance. Most of the studies that implicate acyl-CoA, lysophosphatidic acid, phosphatidic acid, diacylglycerol, or ceramide rely on indirect associations. Convincing data to support the hypothesis that specific lipid intermediates initiate pathways that alter insulin signaling will require studies in which the concentration of each purported signaling molecule can be manipulated independently.

Supplementary key words Hepatic steatosis • diacylglycerol • phosphatidic acid • lysophosphatidic acid • ceramide

Abbreviations: ACC, acetyl-CoA carboxylase; ACSL, acyl-CoA synthetase; AGPAT, 1-acylglycerol-3-phosphate acyltransferase; ChREBP, carbohydrate-responsive element-binding protein; CPT, carnitine-palmitoyltransferase; DAG, diacylglycerol; DGAT, DAG acyltransferase; GPAT, glycerol-3-phosphate acyltransferase; HF, high fat; HF-SD, HF safflower oil diet; IR, insulin resistance; IRS, insulin receptor substrate; KO, knock out; LCAD, long chain acyl-CoA dehydrogenase; LPA, lysophosphatidic acid; LXR, liver-X-receptor; MCAD, medium chain acyl-CoA dehydrogenase; NAFLD, nonalcoholic fatty liver disease; DNL, de novo lipogenesis; PA, phosphatidic acid; PAP, phosphatidic acid phosphatase; PKC, protein kinase C; PPAR, peroxisome proliferator-activated receptor; TAG, triacylglycerol; SCAD, short-chain acyl-CoA dehydrogenase; SCD, stearoyl-CoA desaturase; SREBP, sterol regulatory element binding protein; TCA, tricarboxylic acid; WT, wild type; VLCAD, long chain acyl-CoA dehydrogenase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Webpages: