P179 CARDIOMETABOLIC DYSFUNCTIONS IN THE OFFSPRING OF FRUCTOSE-OVERLOADED RATS: EVIDENCE FOR THE CHOLINERGIC ANTI-INFLAMMATORY REFLEX

Background: Studies have reported an increase in the consumption of processed foods high in fructose (F), which has been associated with the development of metabolic syndrome. The cholinergic anti-inflammatory reflex (CAT) pathway appears to play an important role in this condition. This study investigated the role of the CAT pathway by splenic and vagal denervation (D) and treatment with galantamine (GAL) on cardiometabolic and autonomic parameters in the offspring of rats subjected to chronic fructose consumption. Methods: Wistar rats (parents) were given fructose (10% drinking water) or water for 60 days. The rats were then mated and the fructose overload was maintained for females until the end of lactation. The offspring were randomized into 4 groups (n=10/5 per sex): Control (C), F, F+GAL, and F+D+GAL. GAL (5 mg/kg), an acetylcholinesterase inhibitor, was administered 30 days by gavage. D was performed at 21 days. The offspring were evaluated at 51 days. Results: Compared with the C group (3.63±0.24 mg/dl/%/min), the F and F+D+GAL groups (2.8±0.20 and 2.9±0.14 mg/dl/%/min) had a worsening of insulin sensitivity. The F+GAL (370±79 mg) and F+D+GAL groups (310±75 mg) had reduced adipose tissue compared to the C (708±121 mg) and F (980±160 mg) groups. The F and F+D+GAL groups (vs. C group) had increased mean arterial pressure (AP) (114±1.9 and 115±1.4 vs. 101±2.2mmHg), heart rate (381±5 and 369±5 vs. 343±10bpm), and low frequency component of systolic AP (4.95±0.49 and 3.33±0.23 vs. 1.62±0.2mmHg2). The F+GAL group had an increase in cardiac vagal modulation (HF-PI and RMSSD). F and F+D+GAL groups (vs. C) had impairment of baroreflex (-3.24±0.26 and -3.48±0.1 vs. -3.93±0.1bpm/mmHg), and F+GAL group improved this parameter. Conclusion: Our data provide evidence for the involvement of CAT in cardiometabolic dysfunction in the offspring of parents exposed to chronic fructose consumption. Such findings highlight the importance of therapeutic strategies that improve autonomic modulation to prevent early changes in offspring of metabolically overburdened parents. Financial support: FAPESP(2022/04050-1), CNPq, CAPES-PROSUP.