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The Chemical Chaperone Tauroursodeoxycholic Acid Alleviates Cardiac Contractile Dysfunction in Obesity: Role of Endoplasmic Reticulum‐Stress in Cardiac Functionality
Author(s) -
Isik Asli Fahriye Ceylan,
Ren Jun,
Sreejayan Nair
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.573.8
Subject(s) - tauroursodeoxycholic acid , endoplasmic reticulum , unfolded protein response , medicine , endocrinology , chemical chaperone , serca , insulin , chemistry , biochemistry , atpase , enzyme
Endoplasmic reticulum (ER)‐stress has been implicated in the pathophysiology diabetes and obesity. The aim of this study was to investigate whether ER‐stress is involved in the obesity‐induced cardiac dysfunction (CD) and to assess the effect of an ER‐chaperone tauroursodeoxycholic acid (TUDCA). Seven‐week old obese (ob/ob) and their lean counterparts were randomly received TUDCA (50mg/kg, orally, 5 weeks) or vehicle. Oral glucose tolerance test (OGTT), echocardiographic analysis and cardiomyocyte function were assessed. Sarco(endo)plasmic reticulum calcium (SERCA) activity measured by 45Ca2+ uptake. Expressions of markers of ER‐stress and insulin signaling pathway were determined. TUDCA‐treated ob/ob mice displayed lower blood glucose levels following OGTT vs. vehicle treatment. Ob/ob mice exhibited increased diastolic wall thickness, diastolic and systolic diameters and decreased fractional shortening vs. lean mice, all of which were attenuated by TUDCA. TUDCA treatment alleviated the compromised cardiomyocyte mechanical functions and SERCA activity observed in ob/ob mice. Markers of ER‐stress and insulin signaling pathway were altered in the hearts of ob/ob mice vs. lean controls which were attenuated by TUDCA. Our data suggest that ER‐stress plays a pivotal role in CD and attenuating ER‐stress may represent a potential therapeutic strategy in obesity‐induced CD.