What is the clinical evidence from this study?

Study design: Other. Population: Left ventricular pressure overload. Intervention: High-fat diet vs. Standard diet (10% fat). Primary outcome: Survival after transverse aortic constriction (p=<0.02).

October 31, 2008Open Access

A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload

Q: What are the key findings of this study?

A short duration of high-fat diet induced insulin resistance and significantly decreased survival (43% vs 75%) and exacerbated left ventricular dysfunction after pressure overload in mice.

Key Result

A short duration of high-fat diet induced insulin resistance and significantly decreased survival (43% vs 75%) and exacerbated left ventricular dysfunction after pressure overload in mice.

Structured PICO

Does a short duration of high-fat diet exacerbate adverse left ventricular remodeling and dysfunction after pressure overload in C57BL6 male mice?

Population

C57BL6 male mice subjected to a high-fat or standard diet for 9 days followed by transverse aortic constriction to evaluate left ventricular remodeling and function.

Intervention

High-fat diet (HFD, 60% fat from lard) for 9 days followed by transverse aortic constriction (TAC).

Comparator

Standard diet (SD, 10% fat) for 9 days followed by transverse aortic constriction (TAC).

Outcome

Left ventricular size and function assessed by serial echocardiography before and 7, 21, and 28 days after TAC.surrogate

A short duration of high-fat diet induces insulin resistance and exacerbates adverse left ventricular remodeling, dysfunction, and mortality following pressure overload in mice.

Main Result

Absolute Event Rate: 43% vs 75%

p-value: p=<0.02

Limitations

The absence of plasma glucose measurements during the micro-PET experiments is a limitation of the study.
The measurement of the MCD gene expression is insufficient to conclude that free fatty acid oxidation is modified.

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.

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