AKC Seminar: The role of PGC-1α in the regulation of skeletal muscle cell plasticity in health and disease

August Krogh Club Seminar

Associate Professor of Pharmacology Christoph Handschin, PhD

Biozentrum, Focal Area Growth and Development University of Basel, Switzerland.


Skeletal muscle has an enormous capacity to adapt to external stimuli such as physical activity, nutrient supply, temperature and oxygen levels by altering signaling pathways, metabolic properties, myofibrillar function and protein synthesis and degradation rates. The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a regulatory nexus of endurance training in muscle. Every major signaling pathway activated in a contracting muscle fiber converges on this transcriptional coactivator at some point; in turn, PGC-1α controls the biological programs that are necessary to evoke an endurance trained phenotype in skeletal muscle. We are both interested in studying how upstream signaling is integrated and coordinated to activate PGC-1α as well as deconvoluting the transcriptional networks by which PGC-1α regulates distinct biological functions in this tissue. For example, we investigate the crosstalk between muscle fibers and the motor neuron to study how morphological and functional properties of the neuromuscular junction (NMJ) are determined in a PGC-1α-dependent manner.

Furthermore, we are interested in the metabolic remodeling and selective energy substrate usage in inactive and trained muscle, respectively. Intriguingly, many of the pathologies that are linked to an aberrant substrate usage have been associated with a persistent, sterile inflammation, most prominently type 2 diabetes. In white adipose tissue, a close link between metabolic regulation and macrophage infiltration and activation has been proposed. We therefore studied whether such a link also exists in skeletal muscle since we have previously shown that muscle-specific loss-of-function animal models for PGC-1α, which exhibit a phenotype that is remarkably similar to pathological inactivity, suffer from elevated tissue as well as systemic inflammation. Our findings suggest that the PGC-1s negatively modulate the transcriptional activity of the nuclear factor κB (NFκB) in muscle cells. Together, our results imply that the PGC-1 coactivators are the molecular mediators of the mutual regulation of metabolism and inflammation in skeletal muscle.


23 October 2013

14:00-15:00: Seminar and discussion
15:00-15:30: Post seminar servings and socializing


Auditorium 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen


Participation is free, but please register here.

For PhD students

PhD students participating in August Krogh seminars receive 0,2 ECTS per seminar


Christian Frøsig, CFrosig@ifi.ku.dk, mobile +45 2875 1617

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