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Angiogenesis

, Volume 16, Issue 2, pp 297–307 | Cite as

High-fat feeding induces angiogenesis in skeletal muscle and activates angiogenic pathways in capillaries

  • Mika Silvennoinen
  • Rita Rinnankoski-Tuikka
  • Mikael Vuento
  • Juha J. Hulmi
  • Sira Torvinen
  • Maarit Lehti
  • Riikka Kivelä
  • Heikki Kainulainen
Original Paper

Abstract

High-fat diet (HFD) increases fatty acid oxidation in skeletal muscles. We hypothesized that this leads to increased oxygen demand and thus to increased capillarization. We determined the effects of high-fat diet on capillarization and angiogenic factors in skeletal muscles of mice that were either active or sedentary. Fifty-eight C57BL/6 J mice were divided into four groups: low-fat diet sedentary (LFS), low-fat diet active (LFA), high-fat diet sedentary (HFS), and high-fat diet active (HFA). The mice in active groups were housed in cages with running wheels and the sedentary mice were housed in similar cages without running wheels. After 19 weeks HFS, LFA and HFA had higher capillary density and capillary-to-fiber-ratio in quadriceps femoris muscles than LFS. Capillarization was similar in HFS and HFA. To reveal possible mechanisms of HFD induced angiogenesis, we measured protein and mRNA levels of angiogenic factors VEGF-A, HIF-1α, PGC-1α and ERRα. VEGF-A protein levels were higher in muscles of HFS, LFA and HFA compared to LFS. However, no significant differences were observed between HFA and HFS. Protein levels of HIF-1α, PGC-1α, and ERRα were similar in all groups. However, the mRNA expression of HIF-1α and VEGF-A was up-regulated in capillaries but not in muscle fibers of HFS. The sedentary and active mice groups had similar mRNA expression levels of angiogenesis regulators studied. We conclude that high-fat feeding induces angiogenesis in skeletal muscle and up-regulates the gene expression of HIF-1α and VEGF-A in capillaries.

Keywords

High-fat diet Physical activity Exercise Capillarization 

Abbreviations

BSA

Bovine serum albumin

cDNA

Complementary DNA

CSA

Cross sectional area

DTT

Dithiothreitol

ECL

Enhanced chemiluminescence

EDTA

Ethylenediaminetetraacetic acid

ERRα

Estrogen-related receptor alpha

FFA

Free fatty acid

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

HFD

High-fat diet

HFA

High-fat active

HFS

High-fat sedentary

HIF-1α

Hypoxia-inducible factor 1, alpha subunit

HIF-1β

Hypoxia-inducible factor 1, beta subunit

HOMA-IR

Homeostatic model assessment of insulin resistance

LCM

Laser capture microdissection

LFD

Low-fat diet

LFA

Low-fat active

LFS

Low-fat sedentary

MQF

Musculus quadriceps femoris

PBS

Phosphate buffered saline

PCR

Polymerase chain reaction

PGC-1α

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PMSF

Phenylmethylsulfonyl fluoride

PVDF

Polyvinylidene difluoride

SDS

Sodium dodecyl sulfate

SDS-PAGE

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

TBS-T

Tris-buffered saline + Tween 20

Tris–HCl

Tris(hydroxymethyl)aminomethane-hydrogen chloride

VEGF-A

Vascular endothelial growth factor A

Notes

Acknowledgments

The authors would like to thank Aila Ollikainen and Lauri Stenroth for their skillful help in the laboratory. The study was financially supported by the Finnish Ministry of Education and Culture (50/627/2010) and the Academy of Finland (125209). Support from the National Doctoral Programme of Musculoskeletal Disorders and Biomaterials (TBDP) is also acknowledged.

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Mika Silvennoinen
    • 1
    • 2
  • Rita Rinnankoski-Tuikka
    • 1
    • 2
  • Mikael Vuento
    • 3
  • Juha J. Hulmi
    • 1
  • Sira Torvinen
    • 1
  • Maarit Lehti
    • 2
  • Riikka Kivelä
    • 1
    • 2
    • 4
  • Heikki Kainulainen
    • 1
    • 2
  1. 1.Department of Biology of Physical Activity, Neuromuscular Research CenterUniversity of JyväskyläJyväskyläFinland
  2. 2.LIKES Research CenterJyväskyläFinland
  3. 3.School of MedicineUniversity of TampereTampereFinland
  4. 4.Molecular Cancer Biology Program, Biomedicum HelsinkiUniversity of HelsinkiHelsinkiFinland

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