title: A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload.
abstract: Insulin resistance is an increasingly prevalent condition in humans that frequently clusters with disorders characterized by left ventricular (LV) pressure overload, such as systemic hypertension. To investigate the impact of insulin resistance on LV remodeling and functional response to pressure overload, C57BL6 male mice were fed a high-fat (HFD) or a standard diet (SD) for 9 days and then underwent transverse aortic constriction (TAC). LV size and function were assessed in SD- and HFD-fed mice using serial echocardiography before and 7, 21, and 28 days after TAC. Serial echocardiography was also performed on nonoperated SD- and HFD-fed mice over a period of 6 wk. LV perfusion was assessed before and 7 and 28 days after TAC. Nine days of HFD induced systemic and myocardial insulin resistance (assessed by myocardial 18F-fluorodeoxyglucose uptake), and myocardial perfusion response to acetylcholine was impaired. High-fat feeding for 28 days did not change LV size and function in nonbanded mice; however, TAC induced greater hypertrophy, more marked LV systolic and diastolic dysfunction, and decreased survival in HFD-fed compared with SD-fed mice. Compared with SD-fed mice, myocardial perfusion reserve was decreased 7 days after TAC, and capillary density was decreased 28 days after TAC in HFD-fed mice. A short duration of HFD induces insulin resistance in mice. These metabolic changes are accompanied by increased LV remodeling and dysfunction after TAC, highlighting the impact of insulin resistance in the development of pressure-overload-induced heart failure.
authors.affiliation: Cardiac Ultrasound Laboratory, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Raher
authors.forename: Helene B
authors.initials: HB
authors.lastname: Thibault
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.forename: Darshini
authors.initials: D
authors.lastname: Kuruppu
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimizu
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Brownell
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Blake
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.forename: Genevieve
authors.initials: G
authors.lastname: Derumeaux
authors.forename: Michael H
authors.initials: MH
authors.lastname: Picard
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Marielle
authors.initials: M
authors.lastname: Scherrer-Crosbie
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology; D005355:Fibrosis; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D006439:Hemodynamics; D006973:Hypertension / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055414:Myocardial Perfusion Imaging; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D012307:Risk Factors; D013997:Time Factors; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D020257:Ventricular Remodeling
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D014665:Vasodilator Agents; D004280:Dobutamine; D000109:Acetylcholine