Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy

Abstract

Currently, a high carbohydrate/low fat diet is recommended for patients with hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate plays in hypertension and the development of pathological left ventricular hypertrophy (LVH) has not been well characterized. Recent studies demonstrate that LVH can also be triggered by activation of insulin signaling pathways, altered adipokine levels, or the activity of peroxisome proliferator-activated receptors (PPARs), suggesting that metabolic alterations play a role in the pathophysiology of LVH. Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy. PPARs also activate cardiac gene expression and growth and are stimulated by fatty acids and consumption of a high fat diet. Dietary intake of fats and carbohydrate and the resultant effects of plasma insulin, adipokine, and lipid concentrations may affect cardiomyocyte size and function, particularly in the setting of chronic hypertension. This review discusses potential mechanisms by which dietary carbohydrates and fats ca affect cardiac growth, metabolism, and function, mainly in the context of pressure overload-induced LVH.

Figure 1

Proposed schematic depiction of activation of LV hypertrophy by insulin- and fatty acid-mediated signaling pathways. In addition to the “classical” mediators of LVH (adrenergic signalling, endothelin, renin-angiotensin system, etc.) dietary macronutrients can be involved in the hypertrophic response. Insulin enhances Akt-stimulated protein synthesis by activating mTOR and p70s6k., and inhibiting GSK-3β. Akt inhibits protein breakdown through inhibition of FOXO. Upstream of Akt, PI3K can also be activated by signaling mechanisms linked to G-protein coupled receptor stimulation (e.g. Ras, MAPK, ERK, etc) as well as AMP kinase (AMPK). The adiponkines leptin and adiponectin can affect hypertrophy through their actions on ERK and AMPK. PPAR/RXR/PGC1 activates expression of genes involved in cardiac fatty acid oxidation and mitochondrial biogenesis, and can stimulate hypertrophy under some conditions (transgenic over-expression or pharmacologic stimulation with high doses of agonist).

Figure 2

Schematic speculation of how macronutrient intake might influence LV hypertrophy and subsequent dysfunction during pressure overload. Pressure overload stimulates LVH via Akt/mTOR dependent and independent mechanisms, and chronic LVH progresses to LV remodeling and subsequent heart failure. vvEating a diet that is high in carbohydrate (particular simple sugar) and low in fat will increase plasma insulin and activate hypertrophic growth pathways through stimulation of insulin receptors (IR), and activation of Akt and mTOR. On the other hand, a low carbohydrate/high fat diet will reduce result in low plasma insulin concentration and less activation stimulation of insulin mediate growth, and will elevate plasma fatty acid, resulting in greater activation of the PPAR pathway.