Early overnutrition is associated with cardiometabolic alterations in adulthood, likely attributed to reduced insulin sensitivity due to its crucial role in the cardiovascular system. This study aimed to assess the long-term effects of early overnutrition on the development of cardiovascular insulin resistance. An experimental childhood obesity model was established using male Sprague Dawley rats. Rats were organized into litters of 12 pups/mother (L12-Controls) or 3 pups/mother (L3-Overfed) at birth. After weaning, animals from L12 and L3 were housed three per cage and provided ad libitum access to food for 6 months. L3 rats exhibited elevated body weight, along with increased visceral, subcutaneous, and perivascular fat accumulation. However, heart weight at sacrifice was reduced in L3 rats. Furthermore, L3 rats displayed elevated serum levels of glucose, leptin, adiponectin, total lipids, and triglycerides compared to control rats. In the myocardium, overfed rats showed decreased IL-10 mRNA levels and alterations in contractility and heart rate in response to insulin. Similarly, aortic tissue exhibited modified gene expression of TNFα, iNOS, and IL-6. Additionally, L3 aortas exhibited endothelial dysfunction in response to acetylcholine, although insulin-induced relaxation remained unchanged compared to controls. At the molecular level, L3 rats displayed reduced Akt phosphorylation in response to insulin, both in myocardial and aortic tissues, whereas MAPK phosphorylation was elevated solely in the myocardium. Overfeeding during lactation in rats induces endothelial dysfunction and cardiac insulin resistance in adulthood, potentially contributing to the cardiovascular alterations observed in this experimental model.

In a previous clinical trial, it was shown that a probiotic blend (Bifidobacterium longum CECT 7347 (Esflorin1™), Lacticaseibacillus rhamnosus CECT 8361 (BPL15) and Lacticaseibacillus casei CECT 9104 (BPL4)) reduced oxidative stress in males engaging in intense exercise. The present study evaluated whether the probiotic blend’s functional properties are preserved after heat treatment and investigated the underlying mechanism of action using preclinical models. The antioxidant, immunomodulatory and intestinal effects of the heat-treated and probiotic blends were assed using in vitro assays and Caenorhabditis elegans (C. elegans) models. The heat-treated blend preserved the antioxidant activity by scavenging free radicals, reducing intracellular reactive oxygen species and enhancing survival in C. elegans under oxidative stress, possibly via sod-3 upregulation in the CF1553 strain. It also enhanced mitochondrial biogenesis and ATP production in C2C12 via AMPK phosphorylation. Both versions attenuated a gut inflammatory response, improved intestinal barrier in Caco-2 cells and C. elegans and exhibited immunomodulatory activity in U937 macrophages at the tested concentrations. These findings support the heat-treated blend as a promising postbiotic supplement to manage oxidative stress and other physiological alterations associated with intense exercise.