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Dietary Fat and Sugar Differentially Affect Beta‐Adrenergic Stimulation of Cardiac ERK and AKT Pathways in Mice Subjected to High‐Calorie Feeding
Author(s) -
Ashraf Sadia,
Yilmaz Gizem,
Chen Xu,
Harmancey Romain
Publication year - 2020
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.2020.34.s1.04438
Subject(s) - medicine , endocrinology , protein kinase b , sugar , calorie , phosphorylation , insulin , chemistry , biology , biochemistry
. High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear. The goal of this study was to investigate the mechanisms by which high dietary fat and sugar levels affect cardiac growth regulatory pathways in the mouse heart. Methods . Nine‐week‐old male C57BL/6 mice ( n = 20/group) were fed a standard rodent diet (STD; 3.0 kcal/g), a high‐fat diet (HFD; 5.24 kcal/g), a high‐fat and high‐sugar Western diet (WD; 4.73 kcal/g), a high‐sugar diet with mixed carbohydrates (HCD; 3.85 kcal/g), or a high‐sucrose diet (HSD; 3.85 kcal/g). Body composition was assessed weekly by EchoMRI. Whole‐body glucose utilization was assessed with an intraperitoneal glucose tolerance test. After six weeks on diets, mice were treated with saline or 20 mg/kg isoproterenol (ISO) and the activity of cardiac growth regulatory pathways was analyzed by immunoblotting. One‐ or two‐way ANOVA was used for statistical comparisons. Results . Compared with STD, HFD increased body fat mass 4.5‐fold ( P < 0.0001), induced glucose intolerance ( P < 0.0001), and increased insulin levels 3.6‐fold ( P < 0.0001), thereby enhancing basal and ISO‐stimulated AKT phosphorylation at both threonine 308 and serine 473 residues (+37–100%; P < 0.05). Both HCD and HSD potentiated ISO‐mediated stimulation of the glucose‐sensitive kinases PYK2 (>50%; P < 0.05) and ERK (>30%; P < 0.05), thereby leading to increased phosphorylation of protein synthesis regulator S6K1 at threonine 389 residue (≥70%; P < 0.05). All these anthropometric, metabolic and cardiac growth signaling alterations occurred simultaneously in WD‐fed mice. Conclusions . The results indicate that dietary fat and sugar affect cardiac cell growth signaling pathways in C57BL/6 mice through distinct and additive mechanisms. The findings may provide new insights into the role of overnutrition in pathological remodeling of the heart. Support or Funding Information This work was supported by grants R01HL136438, P20GM104357 and P01HL051971 from the National Institutes of Health.