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PMID: 16790840 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity.

Journal of lipid research ·Vol. 47 ·No. 9 ·2006-09-00 ·Pages 2028-41

Wang Y, Botolin D, Xu J, Christian B, Mitchell E, Jayaprakasam B, Nair MG, Nair M, Peters JM, Peters JM, Busik JV, Busik J, Olson LK, Jump DB

Abstract

Fatty acid elongases and desaturases play an important role in hepatic and whole body lipid composition. We examined the role that key transcription factors played in the control of hepatic elongase and desaturase expression. Studies with peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice establish that PPARalpha was required for WY14643-mediated induction of fatty acid elongase-5 (Elovl-5), Elovl-6, and all three desaturases [Delta(5) desaturase (Delta(5)D), Delta(6)D, and Delta(9)D]. Increased nuclear sterol-regulatory element binding protein-1 (SREBP-1) correlated with enhanced expression of Elovl-6, Delta(5)D, Delta(6)D, and Delta(9)D. Only Delta(9)D was also regulated independently by liver X receptor (LXR) agonist. Glucose induction of l-type pyruvate kinase, Delta(9)D, and Elovl-6 expression required the carbohydrate-regulatory element binding protein/MAX-like factor X (ChREBP/MLX) heterodimer. Suppression of Elovl-6 and Delta(9)D expression in livers of streptozotocin-induced diabetic rats and high fat-fed glucose-intolerant mice correlated with low levels of nuclear SREBP-1. In leptin-deficient obese mice (Lep(ob/ob)), increased SREBP-1 and MLX nuclear content correlated with the induction of Elovl-5, Elovl-6, and Delta(9)D expression and the massive accumulation of monounsaturated fatty acids (18:1,n-7 and 18:1,n-9) in neutral lipids. Diabetes- and obesity-induced changes in hepatic lipid composition correlated with changes in elongase and desaturase expression. In conclusion, these studies establish a role for PPARalpha, LXR, SREBP-1, ChREBP, and MLX in the control of hepatic fatty acid elongase and desaturase expression and lipid composition.

MeSH Terms
Acetyltransferases/genetics,metabolism Adult Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics,metabolism Diabetes Mellitus/genetics,metabolism,pathology Fatty Acid Desaturases/genetics,metabolism Fatty Acid Elongases Female Glucose/pharmacology Humans Hydrocarbons, Fluorinated Insulin/pharmacology Leptin/deficiency,genetics Liver/cytology,drug effects,metabolism Male Mice Mice, Inbred C57BL Mice, Obese Middle Aged Obesity/chemically induced,genetics,metabolism PPAR alpha/antagonists & inhibitors,metabolism Pyrimidines/pharmacology Rats Rats, Sprague-Dawley Sterol Regulatory Element Binding Protein 1/genetics,metabolism Sulfonamides/pharmacology
Chemicals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ELOVL5 protein, human ELOVL6 protein, human Elovl6 protein, mouse Hydrocarbons, Fluorinated Insulin Leptin Mlxipl protein, rat PPAR alpha Pyrimidines Sterol Regulatory Element Binding Protein 1 Sulfonamides TO-901317 pirinixic acid Fatty Acid Desaturases Acetyltransferases Fatty Acid Elongases Glucose
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Wang Yun
Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
Botolin Daniela
Xu Jinghua
Christian Barbara
Mitchell Ernestine
Jayaprakasam Bolleddula
Nair Muraleedharan G
Nair Muraleedharan
Peters Jeffrey M
Peters Jeffery M
Busik Julia V
Busik Julia
Olson L Karl
Jump Donald B
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Article Info
Journal
Journal of lipid research
Abbr.
J Lipid Res
ISSN
0022-2275
DOI
10.1194/jlr.M600177-JLR200
Published
2006-09-00
Epub
2006-00-21
Pages
2028-41
Language
English
Region
United States
NLM ID
0376606
PMCID
PMC2764365
Subset
IM
Grants
NIDDK NIH HHS · R01 DK043220 · United States
NIDDK NIH HHS · R01 DK043220-14 · United States
NIDDK NIH HHS · DK-43220 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1194/jlr.M600177-JLR200 PMC Full Text View journal details
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