Excessive Ingestion Of Parental Fructose Causes Autonomic Dysfunction Since Birth In Offspring: Impact on Adulthood

Abstract

The aim this study was to evaluate the effects on hemodynamic, autonomic and inflammatory profile in offspring (from birth to adulthood) of parents submitted to chronic fructose overload. The Fructose genitor group was formed by adult Wistar rats (males and females) that underwent a fructose overload (10%) in drinking water for 60 days. The Control genitor group was formed by adult Wistar rats who were only followed for the same period receiving a standard diet. Mating was carried out and the females continued to receive the same diet (fructose or standard) during all gestation and lactation. On the day of birth, the fructose (F) and control (C) offspring were submitted to an electrocardiogram to analyze heart rate variability (n = 10/group). On the day of weaning two groups were evaluated, the CW group (descendants of the control parents, n = 10) and the FW group (descendants of the fructose parents, n = 10). Another two groups were evaluated 30 days after weaning, group C30 (from control parents, n = 10) and the F30 group (from fructose parents, n = 10). During lifespan, all offspring received a standard diet without fructose. Arterial pressure (AP) were recorded directly. Baroreflex sensitivity was evaluated by increasing dosing of phenylephrine and sodium nitroprusside. Cardiovascular autonomic modulation was evaluated by spectral analysis. Inflammatory profile was measured by ELISA in cardiac tissue. Regarding the autonomic evaluations, the fructose groups presented an impairment from birth to adulthood evidenced by a sympathovagal imbalance (LF/HF) when compared to control groups (F: 0.71 ± 0.08; FW: 0.91 ± 0.08 and F30: 0.72 ± 0.09 vs. C: 0.37 ± 0.04; CW: 0.48 ± 0.07 and C30: 0.38 ± 0.04). Additionally, only the F30 group showed higher vascular sympathetic modulation among groups (4.7 ± 0.6 vs. C30: 2.8 ± 0.4; CW: 1.8 ± 0.4 and FW: 2.9 ± 0.4 mmHg2). Moreover, the fructose groups had a worse tachycardic response when compared to control groups at the same time (FW: −2.8 ± 0.3 and F30: −3.1 ± 0.2 vs. CW: −3.9 ± 0.4 and C30: −4.0 ± 0.1 bpm/mmHg). Finally, group F30 presented worse inflammatory profile compared to group C30, evidenced by the increase of IL‐6 (167.2 ± 9.5 vs C30: 104.9 ± 11.9 pg/ml) and decrease of the IL‐10/TNF alpha ratio (P<0.01). The mean, systolic and diastolic AP was increased only in group F30 when compared to the C30 group (mean AP, F30: 109 ± 1.9 vs. C30: 103 ± 1.3 mmHg). In conclusion, the offspring of parents submitted to fructose overload presented autonomic, hemodynamic and inflammatory cardiovascular dysfunctions. Moreover, the results suggest early autonomic dysfunctions, and these seem to precede hemodynamic and inflammatory changes. These findings suggest cardiovascular autonomic variability as a possible early marker of risk of developing disease in offspring of parents exposed to high fructose consumption. Support or Funding Information FAPESP (2018/17183‐4); CAPES.