Skip to main content

High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.

Publication ,  Journal Article
Lehti, M; Donelan, E; Abplanalp, W; Al-Massadi, O; Habegger, KM; Weber, J; Ress, C; Mansfeld, J; Somvanshi, S; Trivedi, C; Keuper, M ...
Published in: Circulation
November 26, 2013

BACKGROUND: Abnormal glucose metabolism is a central feature of disorders with increased rates of cardiovascular disease. Low levels of high-density lipoprotein (HDL) are a key predictor for cardiovascular disease. We used genetic mouse models with increased HDL levels (apolipoprotein A-I transgenic [apoA-I tg]) and reduced HDL levels (apoA-I-deficient [apoA-I ko]) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle. METHODS AND RESULTS: ApoA-I ko mice exhibited fasting hyperglycemia and impaired glucose tolerance test compared with wild-type mice. Mitochondria isolated from gastrocnemius muscle of apoA-I ko mice displayed markedly blunted ATP synthesis. Endurance capacity during exercise exhaustion test was impaired in apoA-I ko mice. HDL directly enhanced glucose oxidation by increasing glycolysis and mitochondrial respiration rate in C2C12 muscle cells. ApoA-I tg mice exhibited lower fasting glucose levels, improved glucose tolerance test, increased lactate levels, reduced fat mass, associated with protection against age-induced decline of endurance capacity compared with wild-type mice. Circulating levels of fibroblast growth factor 21, a novel biomarker for mitochondrial respiratory chain deficiencies and inhibitor of white adipose lipolysis, were significantly reduced in apoA-I tg mice. Consistent with an increase in glucose utilization of skeletal muscle, genetically increased HDL and apoA-I levels in mice prevented high-fat diet-induced impairment of glucose homeostasis. CONCLUSIONS: In view of impaired mitochondrial function and decreased HDL levels in type 2 diabetes mellitus, our findings indicate that HDL-raising therapies may preserve muscle mitochondrial function and address key aspects of type 2 diabetes mellitus beyond cardiovascular disease.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

November 26, 2013

Volume

128

Issue

22

Start / End Page

2364 / 2371

Location

United States

Related Subject Headings

  • Physical Endurance
  • Muscle, Skeletal
  • Mitochondria, Muscle
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipoproteins, HDL
  • Hyperglycemia
  • Homeostasis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lehti, M., Donelan, E., Abplanalp, W., Al-Massadi, O., Habegger, K. M., Weber, J., … Hofmann, S. M. (2013). High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice. Circulation, 128(22), 2364–2371. https://doi.org/10.1161/CIRCULATIONAHA.113.001551
Lehti, Maarit, Elizabeth Donelan, William Abplanalp, Omar Al-Massadi, Kirk M. Habegger, Jon Weber, Chandler Ress, et al. “High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.Circulation 128, no. 22 (November 26, 2013): 2364–71. https://doi.org/10.1161/CIRCULATIONAHA.113.001551.
Lehti M, Donelan E, Abplanalp W, Al-Massadi O, Habegger KM, Weber J, et al. High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice. Circulation. 2013 Nov 26;128(22):2364–71.
Lehti, Maarit, et al. “High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.Circulation, vol. 128, no. 22, Nov. 2013, pp. 2364–71. Pubmed, doi:10.1161/CIRCULATIONAHA.113.001551.
Lehti M, Donelan E, Abplanalp W, Al-Massadi O, Habegger KM, Weber J, Ress C, Mansfeld J, Somvanshi S, Trivedi C, Keuper M, Ograjsek T, Striese C, Cucuruz S, Pfluger PT, Krishna R, Gordon SM, Silva RAGD, Luquet S, Castel J, Martinez S, D’Alessio D, Davidson WS, Hofmann SM. High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice. Circulation. 2013 Nov 26;128(22):2364–2371.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

November 26, 2013

Volume

128

Issue

22

Start / End Page

2364 / 2371

Location

United States

Related Subject Headings

  • Physical Endurance
  • Muscle, Skeletal
  • Mitochondria, Muscle
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipoproteins, HDL
  • Hyperglycemia
  • Homeostasis