High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age

Abstract

Cottart C, Nivet-Antoine V. High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age. Am J Physiol Heart Circ Physiol 307: H649 -H657, 2014. First published July 11, 2014; doi:10.1152/ajpheart.00291.2014.-High-protein-lowcarbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet. cardiovascular disease; glucose intolerance; high-protein-low-carbohydrate diet CHANGE IN WESTERN lifestyle, with an increasingly fat-rich diet and decreased physical activity, has led to increased overweight and obesity prevalence. Type 2 diabetes and metabolic syndrome have now become endemic (40), leading to increased cardiovascular morbidity and mortality (3). This trend does not concern only mature adults, but also teenagers and young adults, in whom the prevalence of diabetes and being overweight has been increasing (29). Some nutritional strategies have become more and more prevalent, such as highprotein-low-carbohydrate (HP-LC) diets (8). However, their deleterious outcomes on glucose metabolism and arteries have already been underlined (7, 12). Aortas as well as microvessels such as mesenteric arteries are altered with aging. Oxidative stress is one of the most important factors implied in these alterations. The reactive oxygen species (ROS) producers, such as NADPH oxidase, seem to be implied, leading to the vascular inflammation (30,35). Moreover, the deficiency of...

Reduced endothelial thioredoxin‐interacting protein protects arteries from damage induced by metabolic stressin vivo

“…TXNIP fl/fl cdh5 cre mice and their TXNIP fl/fl littermates underwent metabolic stress induced by an HP‐LC diet. After 3 mo of an HP‐LC diet, we found that the HP‐LC‐fed TXNIP fl/fl cdh5 cre mice displayed impaired glucose tolerance similar to that previously observed with this HP‐LC diet (2). The cholesterol profile of HP‐LC‐fed TXNIP fl/fl cdh5 cre mice presented increased total cholesterol and non‐HDL cholesterol levels, associated with a shift from nonlarge to large HDL fractions.…”

“…Dietary interventions to reduce body weight have been widely used, including low‐carbohydrate diets generally high in protein. However, they are known to have deleterious outcomes on glucose metabolism and adverse vascular effects (1, 2).…”

Assessing Cardiac Metabolism

“…384 The deleterious effects of high-protein/low-carbohydrate diets on the cardiovascular system appear to increase with age. 385 On the other hand, experience with the effects of a low-protein diet (0% of energy intake) on the heart is still limited only to branched-chain amino acid metabolism. 386 In short, more research is needed to delineate the effect of specific diets on both the short- and long-term function of the heart.…”

Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion

“…Studies which directly examined the impact of high-fat, high-protein, low-carbohydrate diets on insulin sensitivity have reported conflicting findings, with some showing that such diets lead to glucose intolerance and insulin resistance (2)(3)(4)19), and others reporting it prevents insulin resistance (22), or causes no change in insulin resistance (5,8). While we found a steady progression of insulin-dependent Akt phosphorylation (taken as a measure of insulin effect) in hearts of animals fed CONT diet, there was an unusual response to insulin in the HFLCD-fed heart, with an initially high baseline amount of p-Akt at very low insulin levels and a blunted response as the dose was increased.…”

“…In the 13 C NMR spectrum on the right, K represents isotopomer peaks derived from ketone (3-HB); C represents those derived from carbohydrate (glucose, lactate, and pyruvate). Note that ␤-oxidation of [1][2][3][4][5][6][7][8][9][10][11][12][13] C]palmitate results in seven unlabeled acetyl-CoA fragments and one [1-ketone buffer, high insulin led to decreased FFA oxidation and upregulated ketone oxidation (P Ͻ 0.05 for high insulin compared with low insulin with the same ketone level, perfusion condition, and diet); this effect was not seen with low ketone buffer. At the low level insulin buffer, high ketone upregulated FFA oxidation and decreased ketone oxidation (P Ͻ 0.05 in the HFLCD group for high ketone compared with low ketone with the same insulin level, perfusion condition).…”