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Obesity and aging affects skeletal muscle renin–angiotensin system and myosin heavy chain proportions in pre-diabetic Zucker rats

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Abstract

There is a gap in the knowledge regarding regulation of local renin–angiotensin system (RAS) in skeletal muscle during development of obesity and insulin resistance in vivo. This study evaluates the obesity- and age-related changes in the expression of local RAS components. Since RAS affects skeletal muscle remodelling, we also evaluated the muscle fibre type composition, defined by myosin heavy chain (MyHC) mRNAs and protein content. Gene expressions were determined by qPCR and/or Western blot analysis in musculus quadriceps of 3- and 8-month-old male obese Zucker rats and their lean controls. The enzymatic activity of aminopeptidase A (APA) was determined flourometrically. Activation of renin receptor (ReR)/promyelocytic leukaemia zinc finger (PLZF) negative feedback mechanism was observed in obesity. The expression of angiotensinogen and AT1 was downregulated by obesity, while neutral endopeptidase and AT2 expressions were upregulated in obese rats with aging. Skeletal muscle APA activity was decreased by obesity, which negatively correlated with the increased plasma APA activity and plasma cholesterol. The expression of angiotensin-converting enzyme (ACE) positively correlated with MyHC mRNAs characteristic for fast-twitch muscle fibres. The obesity- and age-related alterations in the expression of both classical and alternative RAS components suggest an onset of a new equilibrium between ACE/AngII/AT1 and ACE2/Ang1–7/Mas at lower level accompanied by increased renin/ReR/PLZF activation. Increased APA release from the skeletal muscle in obesity might contribute to increased plasma APA activity. There is a link between reduced ACE expression and altered muscle MyHC proportion in obesity and aging.

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Funding

This study was supported by grants VEGA 2/0174/14 and APVV grants 15-0229 and 15-0565.

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Authors and Affiliations

  1. Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05, Bratislava 4, Slovakia

    Viktória Lóry, Lucia Balážová, Katarína Kršková, Ľubica Horváthová & Štefan Zórad

  2. Chair of Pharmacology, Jagiellonian University Medical College, 31-531, Krakow, Poland

    Rafal Olszanecki & Maciej Suski

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  1. Viktória Lóry
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Contributions

V.L. prepared major parts of the manuscript. V.L. and L.B. carried out western blots analyses, measurements of enzyme activity, conducted real-time PCR analyses and data interpretation. M. S. and L.B. conducted glucose tolerance tests and biochemical analyses. L.H. carried out transcardial perfusion surgery. L.B., K.K. and S.Z. supervised and edited the manuscript. R. O. and S.Z. planned and organized the study and contributed to the revisions and the final drafts of the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Viktória Lóry.

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Experimental procedures involving animals were approved by the Jagiellonian University Ethical Committee on Animal Experiments.

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Lóry, V., Balážová, L., Kršková, K. et al. Obesity and aging affects skeletal muscle renin–angiotensin system and myosin heavy chain proportions in pre-diabetic Zucker rats. J Physiol Biochem 75, 351–365 (2019). https://doi.org/10.1007/s13105-019-00689-1

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