Involvement of the cholinergic anti-inflammatory pathway in early cardiometabolic dysfunctions in offspring of fructose-fed parents

Parental fructose consumption has been associated with early cardiometabolic dysfunction in the offspring, potentially involving autonomic and inflammatory mechanisms related to the cholinergic anti-inflammatory pathway (CAP). Therefore, we investigated whether splenectomy or autonomic splenic denervation could modulate neuroinflammatory and cardiometabolic alterations in offspring of rats exposed to fructose overload. Male and female Wistar rats received 10% fructose in drinking water or a standard diet for a period of 60 days, before being mated. Parental fructose overload was maintained until the end of lactation. At 21 days of age, the offspring were allocated into four groups: control, fructose, fructose splenectomized, and fructose splenic autonomic-denervated. Splenectomy and splenic denervation were performed at 21 days of age. Metabolic, hemodynamic and autonomic parameters, systemic inflammation, and pro-oxidant markers were evaluated at 51 days of life. Offspring from fructose-fed parents exhibited reduced insulin sensitivity, increased systolic, diastolic, and mean arterial pressure, increased vascular sympathetic modulation, elevated arterial pressure variability, and impaired baroreflex sensitivity. In addition, the fructose group showed increased pro-inflammatory cytokines, NADPH oxidase activity, nitrite, and hydrogen peroxide levels, associated with reduced anti-inflammatory cytokines. The splenectomized and splenic denervation fructose groups attenuated insulin resistance, improved hemodynamic parameters, heart rate, and arterial pressure variability, baroreflex sensitivity, reduced inflammatory cytokines, and attenuated pro-oxidant markers. In conclusion, parental fructose consumption induced early cardiometabolic, autonomic, inflammatory, and redox alterations in the offspring. Moreover, interruption of spleen-related signaling pathways attenuated these dysfunctions, suggesting the involvement of CAP-related mechanisms in the developmental programming induced by parental fructose overload.