Thermal processing of foods at temperatures > 100 °C introduces considerable amounts of advanced glycation end-products (AGEs) into the diet. Maternal dietary exposure might affect the offspring early development and behavioral phenotype in later life. In a rat model, we examined the influence of maternal (F0) dietary challenge with AGEs-rich diet (AGE-RD) during puberty, pregnancy and lactation on early development, a manifestation of physiological reflexes, and behavioral phenotype of F1 and F2 offspring. Mean postnatal day of auditory conduit and eye opening, or incisor eruption was not affected by F0 diet significantly. F1 AGE-RD offspring outperformed their control counterparts in hind limb placing, in grasp tests and surface righting; grandsons of AGE-RD dams outperformed their control counterparts in hind limb placing and granddaughters in surface righting. In a Morris water maze, female AGE-RD F1 and F2 offspring presented better working memory compared with a control group of female offspring. Furthermore, male F2 AGE-RD offspring manifested anxiolysis-like behavior in a light dark test. Mean grooming time in response to sucrose splash did not differ between dietary groups. Our findings indicate that long-term maternal intake of AGE-RD intergenerationally and sex-specifically affects development and behavioral traits of offspring which have never come into direct contact with AGE-RD.

Background: Obesity is a risk factor for several non-communicable diseases and premature death. The Western-type diet, rich in calories and diverse in tastes, smells, and textures, promotes the onset and progression of obesity. We compared the effects of two Western-style palatable obesogenic diets—the cafeteria (CAF) diet, which allows for self-selection of calorie-dense food items consumed by humans, and the fast-food diet (FFD)—composed of a fixed combination of cheeseburgers and fries—on the manifestation of obesity-related complications. Methods: 3-month-old female rats consumed either the control (CTRL), FFD, or CAF diet for 12 months. Body weight was monitored weekly. At the end of the experiment, rats underwent metabolic and behavioral testing. Cardiometabolic markers and those characterizing glycoxidative and carbonyl stress, inflammatory status, and tryptophan metabolism were determined. Results: The CAF rats gain most weight (CTRL: +111 ± 40 g; FFD: +211 ± 77 g; CAF: 316 ± 87 g). CAF feeding produced a classical metabolic syndrome–like profile with severe obesity, insulin resistance, dyslipidemia, and liver steatosis, whereas the FFD model led to moderate obesity with preserved insulin sensitivity but elevated blood pressure and hepatic cholesterol accumulation. Thus, the CAF group developed a severe metabolic syndrome-like pathology assessed as continuous metabolic syndrome z-core (CTRL: −2.3 ± 1.0; FFD: −0.4 ± 1.9; CAF: 3.0 ± 2.4). Despite these differences, both diets promoted neuroinflammation and social deficits, likely mediated through gut microbiota–derived metabolites such as 5-HIAA and indoxyl sulfate. Conclusions: In female rats, self-selected CAF diet drives more severe and distinct pattern of metabolic syndrome-like pathology than a fixed FFD.