Document Detail

Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro.
MedLine Citation:
PMID:  16204368     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Mitochondrial biogenesis is a complex process, and several factors and signaling pathways regulate this process in muscle or brown adipocytes. The aim of the study was to explore pathways affecting mitochondrial biogenesis and fatty acid oxidation (FAO) in human white adipocytes. METHODS: Human preadipocytes obtained from liposuction samples were differentiated in vitro. On the 10th day of differentiation, 4 microM forskolin and 1 microM peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist (pioglitazone, rosiglitazone, or GW 929) or 10 microM PPARalpha agonist (WY-14,643) were added to the media for 96 h. Quantitative real-time PCR was used to determine gene expression/mitochondrial copy number and 14C-labeled palmitate to measure direct energy dissipation. RESULTS: The treatment of adipocytes with forskolin increased mitochondrial copy number and the expression of genes involved in mitochondrial biogenesis (PPARgamma coactivator 1alpha and transcriptional factor A) and fatty acid oxidation (PPARalpha and medium-chain acyl-coenzyme A dehydrogenase). The end (CO2) and intermediate products (14C-labeled acid-soluble products) of FAO were also increased after forskolin treatment. PPARgamma and PPARalpha agonists increased mitochondrial copy number, uncoupling protein 1, medium-chain acyl-coenzyme A dehydrogenase, and carnitine palmitoyltransferase 1, but did not change PPARalpha, PPARgamma coactivator 1alpha, or transcriptional factor A mRNA levels. FAO was higher after rosiglitazone, GW 929, and WY-14,643 but not after pioglitazone treatment. CONCLUSIONS: Pharmacological activation of the cAMP or PPARgamma pathway pushes the white adipocyte down the oxidative continuum. The direct energy-dissipating effects could be significant tools to treat obesity and to improve insulin resistance in type 2 diabetic patients by reduction of fat accumulation in adipocytes or by reprogramming fatty acid metabolism.
Iwona Bogacka; Barbara Ukropcova; Michele McNeil; Jeffrey M Gimble; Steven R Smith
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-04
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  90     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-06     Completed Date:  2006-01-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6650-6     Citation Subset:  AIM; IM    
Pennington Biomedical Research Center, Department of Molecular Endocrinology, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA.
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MeSH Terms
Adipocytes / drug effects,  physiology*,  ultrastructure*
Cells, Cultured
DNA, Mitochondrial
Fatty Acids / metabolism
Forskolin / pharmacology
Gene Dosage / drug effects
Gene Expression
Glycerol / metabolism
Mitochondria / drug effects,  physiology*,  ultrastructure*
Osmolar Concentration
PPAR alpha / agonists
PPAR gamma / agonists,  antagonists & inhibitors
Reg. No./Substance:
0/DNA, Mitochondrial; 0/Fatty Acids; 0/PPAR alpha; 0/PPAR gamma; 56-81-5/Glycerol; 66428-89-5/Forskolin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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