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

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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.

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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

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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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Author notes

  1. Riikka Kivelä

    Present address: Molecular Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland

Authors and Affiliations

  1. Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, P.O. Box 35, 40014, Jyväskylä, Finland

    Mika Silvennoinen, Rita Rinnankoski-Tuikka, Juha J. Hulmi, Sira Torvinen, Riikka Kivelä & Heikki Kainulainen

  2. LIKES Research Center, Jyväskylä, Finland

    Mika Silvennoinen, Rita Rinnankoski-Tuikka, Maarit Lehti, Riikka Kivelä & Heikki Kainulainen

  3. School of Medicine, University of Tampere, Tampere, Finland

    Mikael Vuento

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Correspondence to Heikki Kainulainen.

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Mika Silvennoinen, Rita Rinnankoski-Tuikka contributed equally to this work.

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Silvennoinen, M., Rinnankoski-Tuikka, R., Vuento, M. et al. High-fat feeding induces angiogenesis in skeletal muscle and activates angiogenic pathways in capillaries. Angiogenesis 16, 297–307 (2013). https://doi.org/10.1007/s10456-012-9315-8

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