Enhanced transforming growth factor-beta signaling and fibrogenesis in ovine fetal skeletal muscle of obese dams at late gestation

Yan Huang; Xu Yan; Mei J Zhu; Richard J McCormick; Stephen P Ford; Peter W Nathanielsz; Min Du

doi:10.1152/ajpendo.00015.2010

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Enhanced transforming growth factor-beta signaling and fibrogenesis in ovine fetal skeletal muscle of obese dams at late gestation

Journal article

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Enhanced transforming growth factor-beta signaling and fibrogenesis in ovine fetal skeletal muscle of obese dams at late gestation

Yan Huang, Xu Yan, Mei J Zhu, Richard J McCormick, Stephen P Ford, Peter W Nathanielsz and Min Du

American journal of physiology: endocrinology and metabolism, Vol.298(6), pp.E1254-1260

06/2010

DOI: https://doi.org/10.1152/ajpendo.00015.2010

Handle:

https://hdl.handle.net/2376/109003

PMCID: PMC2886526

PMID: 20371734

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Abstract

Fibronectins - biosynthesis

Male

Tubulin - genetics

Muscle Fibers, Skeletal - metabolism

Procollagen-Proline Dioxygenase - biosynthesis

RNA, Messenger - biosynthesis

Collagen Type I - genetics

Electrophoretic Mobility Shift Assay

Smad7 Protein - genetics

Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - genetics

Tubulin - biosynthesis

RNA, Messenger - genetics

Linear Models

Protein-Lysine 6-Oxidase - biosynthesis

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Obesity - metabolism

Obesity - pathology

Collagen Type I - biosynthesis

Procollagen-Proline Dioxygenase - genetics

Muscle Fibers, Skeletal - pathology

Sheep - metabolism

Fibronectins - genetics

Protein-Lysine 6-Oxidase - genetics

Smad7 Protein - biosynthesis

Transforming Growth Factor beta - metabolism

Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - biosynthesis

Fetus

Signal Transduction

Pregnancy

Maternal obesity (MO) is increasing at an alarming rate. The objective of this study was to evaluate the effect of MO on fibrogenesis in fetal skeletal muscle during maturation in late gestation. Nonpregnant ewes were assigned to a control diet (Con; fed 100% of NRC nutrient recommendations, n = 6) or obesogenic diet (OB; fed 150% of NRC recommendations, n = 6) from 60 days before conception, and fetal semitendenosus (St) muscle was sampled at 135 days of gestation (term 148 days). Total concentration and area of collagen in cross-sections of muscle increased by 27.0 +/- 6.0 (P < 0.05) and 105.1 +/- 5.9% (P = 0.05) in OB compared with Con fetuses. The expression of precursor TGF-beta was 177.3 +/- 47.6% higher, and concentration of phospho-p38 74.7 +/- 23.6% was higher (P < 0.05) in OB than in CON fetal muscle. Increases of 327.9 +/- 168.0 (P < 0.05) and 188.9 +/- 82.1% (P < 0.05), respectively, were observed for mRNA expression of Smad7 and fibronectin in OB compared with Con muscles. In addition, enzymes involved in collagen synthesis, including lysyl oxidase, lysyl hydroxylase 2b, and prolyl 4-hydroxylase-alpha1, were increased by 350.2 +/- 90.0 (P < 0.05), 236.5 +/- 25.2 (P < 0.05), and 82.0 +/- 36.2% (P = 0.05), respectively, in OB muscle. In conclusion, MO-enhanced fibrogenesis in fetal muscle in late gestation was associated with upregulation of the TGF-beta/p38 signaling pathway. Enhanced fibrogenesis at such an early stage of development is expected to negatively affect the properties of offspring muscle because muscle fibrosis is a hallmark of aging.

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Title: Enhanced transforming growth factor-beta signaling and fibrogenesis in ovine fetal skeletal muscle of obese dams at late gestation
Creators: Yan Huang - Center for the Study of Fetal Programming, Department of Animal Science, University ofWyoming, Laramie, WY 82071, USA
Xu Yan
Mei J Zhu
Richard J McCormick
Stephen P Ford
Peter W Nathanielsz
Min Du
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.298(6), pp.E1254-1260
Academic Unit: Department of Animal Sciences
Publisher: United States
Grant note: P20RR016474 / NCRR NIH HHS P01 HD021350 / NICHD NIH HHS
Identifiers: 99900547187201842
Language: English
Resource Type: Journal article