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High-fat diet-induced obesity is associated with increased cardiac telomerase expression but not cell proliferation in the rat

Published online by Cambridge University Press:  12 April 2013

R. Ashrafi
Affiliation:
Department of Obesity & Endocrinology, Institute of Ageing & Chronic Disease, University of Liverpool, Liverpool, L69 3GA
M. A. Yon
Affiliation:
Department of Obesity & Endocrinology, Institute of Ageing & Chronic Disease, University of Liverpool, Liverpool, L69 3GA
J. Yanni-Gerges
Affiliation:
Cardiovascular Research Group, University of Manchester, Manchester, M13 9NT, UK
G. Hart
Affiliation:
Cardiovascular Research Group, University of Manchester, Manchester, M13 9NT, UK
M. Boyett
Affiliation:
Cardiovascular Research Group, University of Manchester, Manchester, M13 9NT, UK
G. K. Davis
Affiliation:
Department of Obesity & Endocrinology, Institute of Ageing & Chronic Disease, University of Liverpool, Liverpool, L69 3GA
L. C. Pickavance
Affiliation:
Department of Obesity & Endocrinology, Institute of Ageing & Chronic Disease, University of Liverpool, Liverpool, L69 3GA
J. P. H Wilding
Affiliation:
Department of Obesity & Endocrinology, Institute of Ageing & Chronic Disease, University of Liverpool, Liverpool, L69 3GA
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Abstract

Type
Abstract
Copyright
Copyright © The Authors 2013

Obesity is a condition of low-grade, chronic inflammation, defined as elevated body weight due to abnormally increased adiposity, commonly from increased dietary intake of saturated fats. Although there are suggested links between obesity, increased cardiovascular mortality and low telomere length( Reference Fyhrquist and Saijonmaa 1 ), no direct relationships between obesity, telomere length and telomerase expression in cardiac tissue have yet been shown( Reference Epel, Lin and Wilhelm 2 ). On the other hand, cardiac hypertrophy has been linked to higher circulating levels of telomerase and reduced telomere length( Reference Serrano and Andres 3 ), but not to a change in cardiac myocyte proliferation. Two phenomenological studies were carried out to explore relationships between obesity and cardiac tissue telomerase gene expression and cell proliferation.

Age-matched male Wistar rats (∼250 g, Charles River, Margate, U.K.) were stratified by body weight and randomly assigned to groups fed for 8 weeks on diets differently enriched in saturated fatty acids (Research Diets, Inc., N.J., U.S.A.; n = 8/group). In Study 1, experimental rats received a high-fat diet (HFD), and in Study 2, a very high-fat diet (VHFD), providing 40% and 60% of energy from fat, respectively. In both studies, control groups received low-fat diets providing 10% of energy from fat. All diets contained equal concentrations of antioxidants. Study 1 rats received the cell proliferation tracer, 5-bromo-2-deoxyuridine (BrdU; Sigma), in their drinking water (1 mg/ml) for the final week of the study. Terminal body weight was measured and white adipose tissue depots dissected and weighed. Samples of left ventricular free wall were dissected and processed histologically for BrdU uptake, as assessed using signal intensity immunofluorescent (IF) measurements (VolocityTM) (Study 1), or by QT-PCR for telomerase (TERT) mRNA expression referenced to 18S rRNA expression (Study 2).

Adiposity was calculated as % epididymal fat mass relative to final body weight. Significance of within-study differences between diet groups were determined by Student's two-sample t-test: *p < 0.05; **p < 0.01 vs. controls.

Both high-fat diets induced obesity (increased adiposity). This was associated with increased cardiac telomerase gene expression, but not cell proliferation. Future work will examine how the two might be related in the same model and whether increased telomerase expression is an adaptive response to obesity.

This work was supported by University Hospital Aintree (R.A.) and the BBSRC-funded cIMB (M.A.Y.).

References

1. Fyhrquist, F & Saijonmaa, O (2012) Ann Med 44, 138142.Google Scholar
2. Epel, ES, Lin, J, Wilhelm, FH et al. (2006) Psychoneuroendocrino 31, 277287.Google Scholar
3. Serrano, AL & Andres, V (2004) Circ Res 19, 575584.CrossRefGoogle Scholar