title: Interleukin-18 mediates cardiac dysfunction induced by western diet independent of obesity and hyperglycemia in the mouse.
abstract: Obesity and diabetes are independent risk factors for heart failure and are associated with the consumption of diet rich in saturated fat and sugar, Western diet (WD), known to induce cardiac dysfunction in the mouse through incompletely characterized inflammatory mechanisms. We hypothesized that the detrimental cardiac effects of WD are mediated by interleukin-18 (IL-18), pro-inflammatory cytokine linked to cardiac dysfunction. C57BL/6J wild-type male mice and IL-18 knockout male mice were fed high-saturated fat and high-sugar diet for 8 weeks. We measured food intake, body weight and fasting glycemia. We assessed left ventricular (LV) systolic and diastolic function by Doppler echocardiography and cardiac catheterization. In wild-type mice, WD induced a significant increase in isovolumetric relaxation time, myocardial performance index and left ventricular end-diastolic pressure, reflecting an impairment in diastolic function, paired with a mild reduction in LV ejection fraction. IL-18 KO mice had higher food intake and greater increase in body weight without significant differences in hyperglycemia. Despite displaying greater obesity, IL-18 knockout mice fed with WD for 8 weeks had preserved cardiac diastolic function and higher left ventricular ejection fraction. IL-18 mediates diet-induced cardiac dysfunction, independent of food intake and obesity, thus highlighting a disconnect between the metabolic and cardiac effects of IL-18.
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.|Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA, USA.|Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Carbone
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.|Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: P J H
authors.initials: PJ
authors.lastname: Lee
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.|Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Mauro
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.|Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA, USA.|School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Mezzaroma
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Buzzetti
authors.affiliation: Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA, USA.|School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Van Tassell
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.|Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Abbate
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA.|Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Toldo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000473:pathology; D003971:Diastole; D066273:Diet, Western / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects; D000073417:Dietary Sugars / Q000009:adverse effects; D004435:Eating; D015150:Echocardiography, Doppler; D002149:Energy Intake; D006333:Heart Failure / Q000097:blood* / Q000209:etiology; D006352:Heart Ventricles; D006943:Hyperglycemia / Q000097:blood*; D007249:Inflammation / Q000097:blood / Q000150:complications*; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium; D009765:Obesity / Q000097:blood / Q000150:complications*; D013318:Stroke Volume; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000209:etiology; D016277:Ventricular Function, Left
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D000073417:Dietary Sugars; D020382:Interleukin-18