Mitochondrial energy deficiency leads to hyperproliferation of skeletal muscle mitochondria and enhanced insulin sensitivity
Abstract
Mitochondrial dysfunction is associated with type II diabetes and metabolic syndrome, but whether it is cause or consequence is debated. By showing that increased mitochondrial respiration can impart glucose tolerance, insulin sensitivity, and resistance to high fat diet (HFD) toxicity, we provide evidence that mitochondria contributes to the etiology of metabolic disease. Inactivation of adenine nucleotide translocator isoform 1 (ANT1) results in proliferation of partially uncoupled muscle mitochondrial respiration, creating a sink for excess calories. Although ANT1-deficient muscle induces expression of Fg f21 , FGF21 level is not elevated in blood, and FGF21 and UCP1 mRNAs are not increased in liver or brown adipose tissue (BAT). If increased mitochondrial respiration prevents HFD toxicity, then decreased mitochondrial respiration may contribute to metabolic disease.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 21, 2017
- Source ID
- 10.1073/pnas.1700997114
Entities
People
- Carlos Dos Santos
- Deborah G Murdock
- Douglas C Wallace
- Gilles Gouspillou
- Jeremy Leipzig
- Martin Picard
- Meagan J. McManus
- Olga Derbeneva
- Russell T. Hepple
- Ryan M. Morrow
- Sébastien Barbat-artigas
Organizations
- Children's Hospital of Philadelphia
- McGill University
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- United States Department of Defense
- University of Pennsylvania
- Université de Montréal
- Université du Québec à Montréal