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Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator‐activated receptor‐γ coactivator‐1α and ‐1β in cultured myotubes
Author(s) -
Espinoza Daniel O.,
Boros Laszlo G.,
Crunkhorn Sarah,
Gami Hiral,
Patti Mary-Elizabeth
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-133728
Subject(s) - lipid metabolism , peroxisome , peroxisome proliferator activated receptor , coactivator , medicine , endocrinology , beta oxidation , chemistry , myogenesis , receptor , fatty acid , biology , metabolism , biochemistry , skeletal muscle , gene , transcription factor
The peroxisome proliferator‐activated receptor γ 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‐1α and PGC‐1β in C2C12 myotubes using adenoviral vectors. Both PGC‐1α and ‐1β 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‐1α and‐1β 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‐1α ( 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‐1α/β ( 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‐1α or ‐1β 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‐γ coactivator‐1α and ‐1β in cultured myotubes. FASEB J. 24, 1003–1014 (2010). www.fasebj.org