Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

Abstract

Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.

Increasing Angiotensin-(1–7) Levels in the Brain Attenuates Metabolic Syndrome–Related Risks in Fructose-Fed Rats

“…In line with previous studies performed in mice, 27,28 rats, 29,30 or humans, 3 FF rats presented slightly increased baseline MAP, impaired baroreflex control of HR, and increased cardiac sympathetic tone, reinforcing the deleterious effects of high fructose intake on cardiovascular system. Interestingly, chronic increase in Ang-(1-7) levels in the brain normalized MAP, the baroreflex control of HR, and reduced cardiac sympathetic activity in FF+A7 rats, as previously observed in DOCA-salt hypertensive rats.…”

“…27,28,35,36 Sympathectomy 37 or pharmacological blockade of sympathetic activity 38,39 prevents the development of insulin resistance, hyperinsulinemia, and hypertension in fructose-fed rats, suggesting that these complications might depend on sympathetic overactivity. However, insulin resistance has been observed with hepatic parasympathectomy or pharmacological blockade.…”

Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development

“…Although high fructose consumption promoted an increase in glycemia compared with control rats, these values were still in the normality range. Other studies, even with longer periods of high-fructose diet, did not find sharp alterations in glycemia (1,6). In fact, this model characterizes an increase in insulin resistance and not hyperglycemia (1,6).…”

Mecanismos associados ao desenvolvimento das complicações do diabetes tipo 2 em camundongos fêmeas ob/ob: papel preventivo do treinamento físico dinâmico aeróbio, resistido ou combinado

“…Com relação aos parâmetros cardiovasculares, não foram observadas diferença em relação à PA e a FC, apesar de alguns estudos em nosso grupo demonstrarem aumento da PA em modelos de síndrome metabólica (BRITO et al, 2008;DE ANGELIS et al, 2012). De fato, um estudo anterior que caracterizou o camundongo ob/ob não demonstrou alteração da PA. Os autores sugeriram que a manutenção da PA poderia estar relacionada ao fato desses animais apresentarem redução da atividade nervosa simpática (YOUNG et al, 1985).…”