Substitution of high-dose sucrose with fructose in high-fat diets resulted in higher plasma concentrations of aspartic acid, cystine, glutamic acid, ornithine and phenylalanine, and higher urine concentrations of arginine and citrulline

Abstract

High fructose intake has been shown to increase circulating alanine transaminase in humans, which could reflect damage to the liver by fructose but could also be linked to higher level of transamination of amino acids in liver. Therefore, we hypothesized that a diet with high content of fructose would affect the amino acid composition in rat plasma and urine differently from a diet with high sucrose content. Because high intake of sucrose and fructose is often accompanied with high intake of saturated fat in the Western-style diet, we wanted to compare the effects of high fructose/sucrose in diets with normal or high content of coconut oil on individual free amino acids plasma and urine. Male Wistar rats were fed diets with normal (10 wt%) or high (40 wt%) content of sucrose or fructose, with normal or high fat content (7 or 22 wt%) and 20 wt% protein (casein). Rats fed high-fructose high-fat diet had higher plasma concentrations of aspartic acid, cystine, glutamic acid, ornithine, and phenylalanine and higher urine concentrations of arginine and citrulline when compared to rats fed high-sucrose high-fat diet. Substituting normal content of sucrose with fructose in the diets had little impact on amino acids in plasma and urine. Serum concentrations of alanine transaminase, aspartate transaminase, and creatinine, and urine cystatin C and T cell immunoglobulin mucin-1 concentrations were comparable between the groups and within normal ranges. To conclude, substituting high-dose sucrose with high-dose fructose in high-fat diets affected amino acid compositions in plasma and urine.

Introduction

In the 1960s and 1970s, intake of fructose was found to be advantageous compared to glucose for diabetic control, as fructose was believed to have less impact on circulation insulin compared to glucose intake and did not affect serum glucose concentration [1,2]. Later, it became evident that high fructose intake affects glucose metabolism and glucose uptake pathways and leads to higher lipogenesis and triacylglycerol synthesis in the liver, and the metabolic disturbances seem to induce the glucose intolerance and insulin resistance commonly observed with high fructose feeding in both humans and animals developing obesity [3]. Conversely, a low fructose intake decreases the glycemic response to glucose loads [3]. The metabolic impact of fructose intake seems to depend on dose, intervention time, age, sex, diet, and medical condition in humans and rats and include increases in adiposity, blood pressure, and circulating uric acid and lactate concentrations, and these effects are most pronounced in subjects with hypertension, hyperinsulinemia, hypertriglyceridemia, non–insulin-dependent diabetes, or high age [2,4,5]. Added fructose as constituent of sucrose (a disaccharide composed of glucose and fructose) or as high-fructose sweeteners (ie, not food such as fruits and vegetables that naturally contain fructose) is the principal driver of type 2 diabetes [6], and the intake of fructose has increased along with the increased prevalence of obesity [7].

Energy intake in the form of carbohydrates has been shown to affect the protein metabolism and utilization [8]; however, little is known about whether high fructose intake affects amino acid metabolism. The metabolism of most amino acids is initiated by transaminases. Alanine transaminase catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate and thus has a key role in the intermediary metabolism of glucose and amino acids. This enzyme is also a major contributor to the steady-state glutamate levels by simultaneously catabolizing and synthesizing glutamine, and it has been speculated that high levels of alanine transaminase in circulation reflect high levels of hepatic transamination of amino acids before fatty liver develops [9]. A meta-analysis of clinical trials revealed that high fructose intake increases circulating alanine transaminase concentrations [10], which could reflect damage to the liver by fructose but could also be linked to changes in amino acid or alanine metabolism. Therefore, the objective of this study was to investigate whether high intake of sucrose or fructose would have different effects on the concentrations of amino acids and other nitrogen-containing compounds in circulation and urine. Because high intake of sucrose and fructose is often accompanied with high intake of saturated fat in the Western-style diet [11], we also wanted to compare the effects of high fructose or sucrose in diets with normal or high content of coconut oil on individual free amino acids and other nitrogen-containing compounds in plasma and urine. We hypothesized that a diet with high content of fructose would affect the amino acid composition in rat plasma and urine differently from a diet with high sucrose content. To test this hypothesis, Wistar rats were fed diets with high fructose or sucrose content combined with normal or high fat content for 4 weeks, and amino acids and other nitrogen-containing compounds were quantified in plasma and urine.