help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on October 4, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1024
A more recent version of this article appeared on December 1, 2005
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
90/12/6650    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bogacka, I.
Right arrow Articles by Smith, S. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bogacka, I.
Right arrow Articles by Smith, S. R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*GLYCERIN

Submitted on May 9, 2005
Accepted on September 23, 2005

Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro

Iwona Bogacka*, Barbara Ukropcova, Michele McNeil, Jeffrey M. Gimble, and Steven R. Smith*

Department of Molecular Endocrinology, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA; Department of Animal Physiology, Faculty of Biology, University of Warmia and Mazury in Olsztyn, Olsztyn-Kortowo, Poland

* To whom correspondence should be addressed. E-mail: iwonab{at}uwm.edu.pl or SmithSR{at}pbrc.edu.

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 liposection samples were differentiated in vitro. On the 10th day of differentiation 4 µM of forskolin, 1 µM of PPAR{gamma} (pioglitazone, rosiglitazone, GW 929) or 10 µM of PPAR{alpha} (WY-14,643) agonists 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 a direct energy-dissipating.

Results: The treatment of adipocytes with forskolin increased mitochondrial copy number and the expression of genes involved in mitochondrial biogenesis (peroxisome proliferators-activated receptor {gamma} coactivator 1 {alpha}, PGC-1{alpha} and transcriptional factor A, TFA) and fatty acid oxidation (peroxisome proliferators-activated receptor {alpha}; PPAR{alpha} and medium-chain acyl-CoA dehydrogenase; MCAD). The end (CO2) and intermediate products (14C-acid soluble products, ASPs) of FAO were also increased after forskolin treatment.

PPAR{gamma} and PPAR{alpha} agonists increased mitochondrial copy number, UCP-1, MCAD and CPT-1 (carnitine palmitoylotransferase 1), but did not change PPAR{alpha}, PGC-1{alpha}, TFA 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 PPAR{gamma} 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.
Key words: peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1{alpha}) • thiazolidinediones • forskolin • fatty acid oxidation • medium-chain acyl-CoA dehydrogenase (MCAD) • peroxisome proliferator-activated receptor alpha (PPAR{alpha})




This article has been cited by other articles:


Home page
 EndocrinologyHome page
S. Crowe, S. M. Turpin, F. Ke, B. E. Kemp, and M. J. Watt
Metabolic Remodeling in Adipocytes Promotes Ciliary Neurotrophic Factor-Mediated Fat Loss in Obesity
Endocrinology, May 1, 2008; 149(5): 2546 - 2556.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
E. E. Kershaw, M. Schupp, H.-P. Guan, N. P. Gardner, M. A. Lazar, and J. S. Flier
PPAR{gamma} regulates adipose triglyceride lipase in adipocytes in vitro and in vivo
Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1736 - E1745.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. Mazzucotelli, N. Viguerie, C. Tiraby, J.-S. Annicotte, A. Mairal, E. Klimcakova, E. Lepin, P. Delmar, S. Dejean, G. Tavernier, et al.
The Transcriptional Coactivator Peroxisome Proliferator Activated Receptor (PPAR){gamma} Coactivator-1{alpha} and the Nuclear Receptor PPAR{alpha} Control the Expression of Glycerol Kinase and Metabolism Genes Independently of PPAR{gamma} Activation in Human White Adipocytes
Diabetes, October 1, 2007; 56(10): 2467 - 2475.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
M. Wortham, M. Czerwinski, L. He, A. Parkinson, and Y.-J. Y. Wan
Expression of Constitutive Androstane Receptor, Hepatic Nuclear Factor 4{alpha}, and P450 Oxidoreductase Genes Determines Interindividual Variability in Basal Expression and Activity of a Broad Scope of Xenobiotic Metabolism Genes in the Human Liver
Drug Metab. Dispos., September 1, 2007; 35(9): 1700 - 1710.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. X. Rong, Y. Qiu, M. K. Hansen, L. Zhu, V. Zhang, M. Xie, Y. Okamoto, M. D. Mattie, H. Higashiyama, S. Asano, et al.
Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet-Fed Mice and Improved by Rosiglitazone
Diabetes, July 1, 2007; 56(7): 1751 - 1760.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
I. Bogacka, T. W. Gettys, L. de Jonge, T. Nguyen, J. M. Smith, H. Xie, F. Greenway, and S. R. Smith
The Effect of {beta}-Adrenergic and Peroxisome Proliferator-Activated Receptor-{gamma} Stimulation on Target Genes Related to Lipid Metabolism in Human Subcutaneous Adipose Tissue
Diabetes Care, May 1, 2007; 30(5): 1179 - 1186.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
P. D. Taylor and L. Poston
Developmental programming of obesity in mammals
Exp Physiol, March 1, 2007; 92(2): 287 - 298.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. A. Lomax, F. Sadiq, G. Karamanlidis, A. Karamitri, P. Trayhurn, and D. G. Hazlerigg
Ontogenic Loss of Brown Adipose Tissue Sensitivity to {beta}-Adrenergic Stimulation in the Ovine
Endocrinology, January 1, 2007; 148(1): 461 - 468.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
N. E. Wolins, B. K. Quaynor, J. R. Skinner, A. Tzekov, M. A. Croce, M. C. Gropler, V. Varma, A. Yao-Borengasser, N. Rasouli, P. A. Kern, et al.
OXPAT/PAT-1 Is a PPAR-Induced Lipid Droplet Protein That Promotes Fatty Acid Utilization
Diabetes, December 1, 2006; 55(12): 3418 - 3428.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2005 by The Endocrine Society