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Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubes.
FASEB J 2010; 24(4):1003-14FJ

Abstract

The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family is a key regulator of mitochondrial function, and reduced mRNA expression may contribute to muscle lipid accumulation in obesity and type 2 diabetes. To characterize the effects of PGC-1 on lipid metabolism, we overexpressed PGC-1alpha and PGC-1beta in C2C12 myotubes using adenoviral vectors. Both PGC-1alpha and -1beta increased palmitate oxidation [31% (P<0.01) and 26% (P<0.05), respectively] despite reductions in cellular uptake [by 6% (P<0.05) and 21% (P<0.001)]. Moreover, PGC-1alpha and -1beta increased mRNA expression of genes regulating both lipid oxidation (e.g., CPT1b and ACADL/M) and synthesis (FAS, CS, ACC1/2, and DGAT1). To determine the net effect, we assessed lipid composition in PGC-1-expressing cells. Total lipid content decreased by 42% in palmitate-loaded serum-starved cells overexpressing PGC-1alpha (P<0.05). In contrast, in serum-replete cells, total lipid content was not significantly altered, but fatty acids C14:0, C16:0, C18:0, and C18:1 were increased 2- to 4-fold for PGC-1alpha/beta (P<0.05). Stable isotope-based dynamic metabolic profiling in serum-replete cells labeled with (13)C substrates revealed both increased de novo fatty acid synthesis from glucose and increased fatty acid synthesis by chain elongation with either PGC-1alpha or -1beta expression. These results indicate that PGC-1 can promote both lipid oxidation and synthesis, with net balance determined by the nutrient/hormonal environment.-Espinoza, D. O., Boros, L. G., Crunkhorn, S., Gami, H., Patti, M.-E. Dual Modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubes.

Authors+Show Affiliations

Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19906680

Citation

Espinoza, Daniel O., et al. "Dual Modulation of Both Lipid Oxidation and Synthesis By Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha and -1beta in Cultured Myotubes." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 24, no. 4, 2010, pp. 1003-14.
Espinoza DO, Boros LG, Crunkhorn S, et al. Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubes. FASEB J. 2010;24(4):1003-14.
Espinoza, D. O., Boros, L. G., Crunkhorn, S., Gami, H., & Patti, M. E. (2010). Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubes. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 24(4), pp. 1003-14. doi:10.1096/fj.09-133728.
Espinoza DO, et al. Dual Modulation of Both Lipid Oxidation and Synthesis By Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha and -1beta in Cultured Myotubes. FASEB J. 2010;24(4):1003-14. PubMed PMID: 19906680.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubes. AU - Espinoza,Daniel O, AU - Boros,Laszlo G, AU - Crunkhorn,Sarah, AU - Gami,Hiral, AU - Patti,Mary-Elizabeth, Y1 - 2009/11/11/ PY - 2009/11/13/entrez PY - 2009/11/13/pubmed PY - 2010/4/29/medline SP - 1003 EP - 14 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 24 IS - 4 N2 - The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family is a key regulator of mitochondrial function, and reduced mRNA expression may contribute to muscle lipid accumulation in obesity and type 2 diabetes. To characterize the effects of PGC-1 on lipid metabolism, we overexpressed PGC-1alpha and PGC-1beta in C2C12 myotubes using adenoviral vectors. Both PGC-1alpha and -1beta increased palmitate oxidation [31% (P<0.01) and 26% (P<0.05), respectively] despite reductions in cellular uptake [by 6% (P<0.05) and 21% (P<0.001)]. Moreover, PGC-1alpha and -1beta increased mRNA expression of genes regulating both lipid oxidation (e.g., CPT1b and ACADL/M) and synthesis (FAS, CS, ACC1/2, and DGAT1). To determine the net effect, we assessed lipid composition in PGC-1-expressing cells. Total lipid content decreased by 42% in palmitate-loaded serum-starved cells overexpressing PGC-1alpha (P<0.05). In contrast, in serum-replete cells, total lipid content was not significantly altered, but fatty acids C14:0, C16:0, C18:0, and C18:1 were increased 2- to 4-fold for PGC-1alpha/beta (P<0.05). Stable isotope-based dynamic metabolic profiling in serum-replete cells labeled with (13)C substrates revealed both increased de novo fatty acid synthesis from glucose and increased fatty acid synthesis by chain elongation with either PGC-1alpha or -1beta expression. These results indicate that PGC-1 can promote both lipid oxidation and synthesis, with net balance determined by the nutrient/hormonal environment.-Espinoza, D. O., Boros, L. G., Crunkhorn, S., Gami, H., Patti, M.-E. Dual Modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubes. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/19906680/Dual_modulation_of_both_lipid_oxidation_and_synthesis_by_peroxisome_proliferator_activated_receptor_gamma_coactivator_1alpha_and__1beta_in_cultured_myotubes_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.09-133728?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -