Abstract Body: Background: Studies have reported that increased consumption of processed foods high in fructose can promote the development of metabolic syndrome. The cholinergic anti-inflammatory pathway (CAP) appears to play an important role in this condition. We investigated how splenic and vagal denervation (D) and treatment with galantamine (GAL) affect cardiometabolic and autonomic parameters in the offspring of rats that consumed fructose chronically. Methods: Wistar rats (parents) were given fructose (10% in drinking water) or water for 60 days. The rats were then mated, and the fructose overload was maintained for the females until the end of lactation. After lactation ended, the offspring were randomized into four groups (n=10, 5/sex): Control (C), F, F+GAL, and F+D+GAL. GAL (5 mg/kg, gavage), an acetylcholinesterase inhibitor, was administered for 30 days. D was performed at day 21. The offspring were evaluated at 51 days. Results: The F and F+D+GAL groups (2.8±0.20 and 2.9±0.14 mg/dL/%/min, respectively) reduced insulin sensitivity compared to the C group (3.63±0.24 mg/dL/%/min). This trend was not observed in the F+GAL group. The F and F+D+GAL groups had increased arterial pressure (AP) compared with the C group (114±1.9 and 115±1.4 vs. 101±2.2 mmHg), as well as increased heart rate (381±5 and 369±5 vs. 343±10 bpm) and the low-frequency component of systolic AP (LF-SAP) (4.95±0.49 and 3.33±0.2 vs. 1.62±0.2 mmHg). The F+GAL group showed increased indexes of cardiac vagal modulation (HF-PI and RMSSD). The F and F+D+GAL groups had impaired tachycardic baroreflex responses (-3.2±0.3 and -3.5±0.1 vs. -3.9±0.1 bpm/mmHg) compared to the C group, but the F+GAL group improved this parameter. The F and F+D+GAL groups showed an increase in TNF-α in the spleen (4.62 ± 0.47 and 4.86±0.59, respectively, vs. C: 2.98±0.29 pg/mg). In the heart, however, the F group showed increased TNF-α (36.51±4.25 vs. 17.02±0.49 pg/mg) and NADPH oxidase (0.066±0.006 vs. 0.046±0.004 nmol/mg protein) compared to the control group. This increase was not observed in the F+GAL and F+D+GAL groups. Conclusion: Our data provide evidence of CAP involvement in cardiometabolic and autonomic dysfunction in offspring of parents exposed to chronic fructose consumption. These findings underscore the importance of therapeutic strategies that enhance autonomic modulation to prevent early alterations in the offspring of metabolically compromised parents.
Financial Support: FAPESP (2022/04050-1), CAPES, CNPq