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Mitochondrial biogenesis and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation by physical activity: intact adipocytokine signaling is required.
Diabetes 2011; 60(1):157-67D

Abstract

OBJECTIVE

Transcriptional peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays a key role in mitochondrial biogenesis and energy metabolism and is suggested to be involved in the exercise-induced increase in mitochondrial content. PGC-1α activity is regulated by posttranslational modifications, among them acetylation or phosphorylation. Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1α activity. RESEARCH DESIGN AND

METHODS

We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1α activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice.

RESULTS

Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice. It enhanced mitochondrial biogenesis in red gastrocnemius muscle, as indicated by increased mRNA expression of transcriptional regulators and primary mitochondrial transcripts, increased mtDNA content, and citrate synthase activity. Parallel to this, we observed AMPK activation, PGC-1α deacetylation, and SIRT1 induction in trained wild-type mice. Although none of these exercise-induced changes were detected in ob/ob mice, comparable effects on mitochondrial respiration were observed. A single exercise session resulted in comparable changes in wild-type mice. These changes remained detectable 6 h after the exercise session but had disappeared after 24 h. Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1α deacetylation.

CONCLUSIONS

Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1α deacetylation. Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1α-independent mechanisms without mtDNA replication.

Authors+Show Affiliations

Institute of Physiology, Justus Liebig University Giessen, Germany.No 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, Non-U.S. Gov't

Language

eng

PubMed ID

20929977

Citation

Li, Ling, et al. "Mitochondrial Biogenesis and Peroxisome Proliferator-activated Receptor-γ Coactivator-1α (PGC-1α) Deacetylation By Physical Activity: Intact Adipocytokine Signaling Is Required." Diabetes, vol. 60, no. 1, 2011, pp. 157-67.
Li L, Pan R, Li R, et al. Mitochondrial biogenesis and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation by physical activity: intact adipocytokine signaling is required. Diabetes. 2011;60(1):157-67.
Li, L., Pan, R., Li, R., Niemann, B., Aurich, A. C., Chen, Y., & Rohrbach, S. (2011). Mitochondrial biogenesis and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation by physical activity: intact adipocytokine signaling is required. Diabetes, 60(1), pp. 157-67. doi:10.2337/db10-0331.
Li L, et al. Mitochondrial Biogenesis and Peroxisome Proliferator-activated Receptor-γ Coactivator-1α (PGC-1α) Deacetylation By Physical Activity: Intact Adipocytokine Signaling Is Required. Diabetes. 2011;60(1):157-67. PubMed PMID: 20929977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial biogenesis and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation by physical activity: intact adipocytokine signaling is required. AU - Li,Ling, AU - Pan,Ruping, AU - Li,Rong, AU - Niemann,Bernd, AU - Aurich,Anne-Cathleen, AU - Chen,Ying, AU - Rohrbach,Susanne, Y1 - 2010/10/07/ PY - 2010/10/9/entrez PY - 2010/10/12/pubmed PY - 2011/2/26/medline SP - 157 EP - 67 JF - Diabetes JO - Diabetes VL - 60 IS - 1 N2 - OBJECTIVE Transcriptional peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays a key role in mitochondrial biogenesis and energy metabolism and is suggested to be involved in the exercise-induced increase in mitochondrial content. PGC-1α activity is regulated by posttranslational modifications, among them acetylation or phosphorylation. Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1α activity. RESEARCH DESIGN AND METHODS We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1α activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice. RESULTS Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice. It enhanced mitochondrial biogenesis in red gastrocnemius muscle, as indicated by increased mRNA expression of transcriptional regulators and primary mitochondrial transcripts, increased mtDNA content, and citrate synthase activity. Parallel to this, we observed AMPK activation, PGC-1α deacetylation, and SIRT1 induction in trained wild-type mice. Although none of these exercise-induced changes were detected in ob/ob mice, comparable effects on mitochondrial respiration were observed. A single exercise session resulted in comparable changes in wild-type mice. These changes remained detectable 6 h after the exercise session but had disappeared after 24 h. Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1α deacetylation. CONCLUSIONS Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1α deacetylation. Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1α-independent mechanisms without mtDNA replication. SN - 1939-327X UR - https://www.unboundmedicine.com/medline/citation/20929977/Mitochondrial_biogenesis_and_peroxisome_proliferator_activated_receptor_γ_coactivator_1α__PGC_1α__deacetylation_by_physical_activity:_intact_adipocytokine_signaling_is_required_ L2 - http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=20929977 DB - PRIME DP - Unbound Medicine ER -