Long-chain fatty acids modify hypertrophic responses of cultured primary neonatal cardiomyocytes

Ahmad Zahabi,Christian F Deschepper

doi:10.1016/s0022-2275(20)31584-4

Abstract

In vivo, the normal heart obtains at least 60% of its energy from lipids and the remainder from glucose. Several lines of evidence indicate that an increase in the utilization of glucose [at the expense of fatty acids (FA)] may play a role in the genesis of hypertrophy. Primary cultures of neonatal cardiomyocytes have been used extensively to study the phenotype of these cells as well as their responses to hormonal hypertrophic agents. Unfortunately, such cultures are most typically cultured in glucose-rich FA-free media, and thus might be hypertrophied to start with. We therefore tested the effects of FA-albumin complexes on three different surrogate end points of hypertrophy of cardiomyocytes. Oleate-albumin complexes decreased the baseline values of all three variables, and increased the relative response of these variables to administration of norepinephrine. Oleate:palmitate-albumin complexes also affected all three variables and their responses to norepinephrine, but the effects differed somewhat from that of oleate-albumin complexes. Our results suggest that addition of long-chain FA, by providing conditions that more closely resemble physiological situations, may optimize the expression of hypertrophic responses in such cells. However, the differences between the effects of oleate and oleate:palmitate also suggest that the precise composition of FA may affect the phenotype of cardiomyocytes and how these cells respond to hypertrophic agents. —Zahabi, A., and C. F. Deschepper. Long-chain fatty acids modify hypertrophic responses of cultured primary neonatal cardiomyocytes.

Highlights

In vivo, the normal heart obtains at least 60% of its energy from lipids and the remainder from glucose
We assessed the effect of each treatment on three different hypertrophy end points, that is, de novo protein synthesis, cell surface area, and secretion of atrial natriuretic factor (ANF) (Fig. 1)
Several lines of evidence indicate that increased glucose utilization and decreased fatty acids (FA) may play a role in the genesis of hypertrophy, and vice versa [4,5,6,7,8,9,10,11]

Summary

Introduction

The normal heart obtains at least 60% of its energy from lipids and the remainder from glucose. Primary cultures of neonatal cardiomyocytes have been used extensively to study the phenotype of these cells as well as their responses to hormonal hypertrophic agents. Given the possible role of glucose uptake in cardiac hypertrophy, cells cultured in such fashion might already display some features of hypertrophy, or show blunted responses to additional hypertrophic stimuli. To test this hypothesis, we verified whether addition of complexes of albumin and FA to the culture medium of primary neonatal cardiomyocytes would affect the responses of cells to hypertrophic agents. Three different end points were used to evaluate hypertrophy responses, that is, de novo protein synthesis, cell surface, and secretion of atrial natriuretic factor (ANF)

Methods

Results

Conclusion