ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P237 | DOI: 10.1530/endoabs.65.P237

Obesity induces cardiac hypertrophy without functional or fibrotic alterations

Elisa Villalobos1,2, Alfredo Criollo3, Gabriele Schiattarella1, Francisco Altamirano1, Thomas Gillette1, Sergio Lavandero1,4 & Joseph Hill5

1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA; 2Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; 3Instituto de Investigación en Ciencias Odontológicas, Facultad Odontología, Universidad de Chile, Santiago, Chile; 4Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Santiago, Chile; 5Department of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, USA

Background: Cardiac fibrosis is a common biological response to cardiovascular injury. Maladaptive cardiac fibrosis as observed in patients with hypertension, obesity or diabetes mellitus contributes to contractile dysfunction and electrophysiological disorders. Currently, there is controversy regarding whetherexposure to a high fat diet (HFD) in isolation induces cardiovascular damage and fibrosis. Here, we set out to explore the contribution of different models of obesity to the development of cardiac fibrosis and cardiovascular remodeling.

Methods: C57BL/6 mice were fed standard chow diet or HFD (60% fat from lard) for 20 and 30 weeks. Adult Ob/Ob mice (genetic model of obesity) were also studied. Mice subjected to severe transverse aortic constriction (sTAC, 28 G needle) for 3 weeks were used as positive control for fibrosis. Fibrosis development was assessed by histological analyses using Masson’s Trichrome and Picrosirius red staining. The levels of fibrosis markers (mRNA and protein) of collagen I, collagen III and fibronectin were determined by RT-qPCR and Western blot. Myocardial function was assessed by echocardiography.

Results: Increased insulin levels, glucose intolerance and obesity were observed after 20 weeks of HFD. However, we did not observe changes in myocardial function (systolic) nor myocardial fibrosis. Long-term exposure to HFD for 30 weeks did not elicit differences in glucose tolerance, myocardial function or cardiac fibrosis. Similar results were observed in the genetic model of obesity. Meanwhile, severe pressure overload model (sTAC) triggered heart failure with reduced ejection fraction and cardiac fibrosis.

Conclusions: These results suggest that myocardial fibrosis observed in patients with metabolic diseases (e.g. obesity and diabetes) requires the presence additional comorbidities (e.g. afterload stress, endothelial damage).

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