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Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals.
Diabetes 2010; 59(6):1407-15D

Abstract

OBJECTIVE

To determine whether the obesity-related decrement in fatty acid oxidation (FAO) in primary human skeletal muscle cells (HSkMC) is linked with lower mitochondrial content and whether this deficit could be corrected via overexpression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha).

RESEARCH DESIGN AND METHODS

FAO was studied in HSkMC from lean (BMI 22.4 +/- 0.9 kg/m(2); N = 12) and extremely obese (45.3 +/- 1.4 kg/m(2); N = 9) subjects. Recombinant adenovirus was used to increase HSkMC PGC-1alpha expression (3.5- and 8.0-fold), followed by assessment of mitochondrial content (mtDNA and cytochrome C oxidase IV [COXIV]), complete ((14)CO(2) production from labeled oleate), and incomplete (acid soluble metabolites [ASM]) FAO, and glycerolipid synthesis.

RESULTS

Obesity was associated with a 30% decrease (P < 0.05) in complete FAO, which was accompanied by higher relative rates of incomplete FAO ([(14)C]ASM production/(14)CO(2)), increased partitioning of fatty acid toward storage, and lower (P < 0.05) mtDNA (-27%), COXIV (-35%), and mitochondrial transcription factor (mtTFA) (-43%) protein levels. PGC-1alpha overexpression increased (P < 0.05) FAO, mtDNA, COXIV, mtTFA, and fatty acid incorporation into triacylglycerol in both lean and obese groups. Perturbations in FAO, triacylglycerol synthesis, mtDNA, COXIV, and mtTFA in obese compared with lean HSkMC persisted despite PGC-1alpha overexpression. When adjusted for mtDNA and COXIV content, FAO was equivalent between lean and obese groups.

CONCLUSION

Reduced mitochondrial content is related to impaired FAO in HSkMC derived from obese individuals. Increasing PGC-1alpha protein levels did not correct the obesity-related absolute reduction in FAO or mtDNA content, implicating mechanisms other than PGC-1alpha abundance.

Authors+Show Affiliations

Department of Exercise and Sport Science, East Carolina University, Greenville, North Carolina, USA. consittl@ecu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

20200320

Citation

Consitt, Leslie A., et al. "Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha Overexpression Increases Lipid Oxidation in Myocytes From Extremely Obese Individuals." Diabetes, vol. 59, no. 6, 2010, pp. 1407-15.
Consitt LA, Bell JA, Koves TR, et al. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals. Diabetes. 2010;59(6):1407-15.
Consitt, L. A., Bell, J. A., Koves, T. R., Muoio, D. M., Hulver, M. W., Haynie, K. R., ... Houmard, J. A. (2010). Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals. Diabetes, 59(6), pp. 1407-15. doi:10.2337/db09-1704.
Consitt LA, et al. Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha Overexpression Increases Lipid Oxidation in Myocytes From Extremely Obese Individuals. Diabetes. 2010;59(6):1407-15. PubMed PMID: 20200320.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals. AU - Consitt,Leslie A, AU - Bell,Jill A, AU - Koves,Timothy R, AU - Muoio,Deborah M, AU - Hulver,Matthew W, AU - Haynie,Kimberly R, AU - Dohm,G Lynis, AU - Houmard,Joseph A, Y1 - 2010/03/03/ PY - 2010/3/5/entrez PY - 2010/3/5/pubmed PY - 2010/8/11/medline SP - 1407 EP - 15 JF - Diabetes JO - Diabetes VL - 59 IS - 6 N2 - OBJECTIVE: To determine whether the obesity-related decrement in fatty acid oxidation (FAO) in primary human skeletal muscle cells (HSkMC) is linked with lower mitochondrial content and whether this deficit could be corrected via overexpression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha). RESEARCH DESIGN AND METHODS: FAO was studied in HSkMC from lean (BMI 22.4 +/- 0.9 kg/m(2); N = 12) and extremely obese (45.3 +/- 1.4 kg/m(2); N = 9) subjects. Recombinant adenovirus was used to increase HSkMC PGC-1alpha expression (3.5- and 8.0-fold), followed by assessment of mitochondrial content (mtDNA and cytochrome C oxidase IV [COXIV]), complete ((14)CO(2) production from labeled oleate), and incomplete (acid soluble metabolites [ASM]) FAO, and glycerolipid synthesis. RESULTS: Obesity was associated with a 30% decrease (P < 0.05) in complete FAO, which was accompanied by higher relative rates of incomplete FAO ([(14)C]ASM production/(14)CO(2)), increased partitioning of fatty acid toward storage, and lower (P < 0.05) mtDNA (-27%), COXIV (-35%), and mitochondrial transcription factor (mtTFA) (-43%) protein levels. PGC-1alpha overexpression increased (P < 0.05) FAO, mtDNA, COXIV, mtTFA, and fatty acid incorporation into triacylglycerol in both lean and obese groups. Perturbations in FAO, triacylglycerol synthesis, mtDNA, COXIV, and mtTFA in obese compared with lean HSkMC persisted despite PGC-1alpha overexpression. When adjusted for mtDNA and COXIV content, FAO was equivalent between lean and obese groups. CONCLUSION: Reduced mitochondrial content is related to impaired FAO in HSkMC derived from obese individuals. Increasing PGC-1alpha protein levels did not correct the obesity-related absolute reduction in FAO or mtDNA content, implicating mechanisms other than PGC-1alpha abundance. SN - 1939-327X UR - https://www.unboundmedicine.com/medline/citation/20200320/Peroxisome_proliferator_activated_receptor_gamma_coactivator_1alpha_overexpression_increases_lipid_oxidation_in_myocytes_from_extremely_obese_individuals_ L2 - http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=20200320 DB - PRIME DP - Unbound Medicine ER -