Early-life adversity has become recognized as an important factor contributing to adult obesity and associated metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction associated with early-life adversity result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination. Interestingly, both early-life adversity and later-life dietary choices affect immune function, favouring pro-inflammatory mechanisms that are associated with obesity-related metabolic dysfunction. To investigate the unique and/or interactive effects of early-life adversity and later-life dietary choices for increased vulnerability to obesity and metabolic dysfunction, and specifically the role of the immune system in this vulnerability, we combined a naturalistic rat model of early-life scarcity-adversity with a rat model of obesity, the cafeteria diet. Our results indicate that early-life adversity alone induces insulin resistance, reduces pancreatic insulin secretion, plasma concentrations of triglycerides and cholesterol, and increases fasting glucose and tumour necrosis factor-α plasma concentrations. Importantly, animals exposed to adverse rearing were more vulnerable to metabolic dysregulation associated with the cafeteria diet, given that they consumed more energy, showed more severe hepatic steatosis and increased concentrations of the pro-inflammatory cytokine interleukin-1β than normally reared animals fed the cafeteria diet. Together, our results suggest that early-life adversity negatively programmes physiological systems that regulate metabolic function and increases vulnerability to obesity and metabolic dysfunction in adulthood. These results highlight the intrinsic relationship between the quality of the early postnatal environment and later-life dietary choices on adult health outcomes.

Metformin hydrochloride (MET) is an oral medication very prescribed for patients with diabetes, with a large part of its metabolites being eliminated in the urine. Basic sanitation systems are not fully effective in removing all the contaminants, promoting contamination to rivers and supply reservoirs. The objective of this study was to test the potential acute and chronic effects of MET on the antioxidant system, mutagenicity effects and tissue damages in the bioindicator D. rerio. The animals were acclimatized and separated into six groups and exposed to different concentrations of MET (0.00, 0.25, 0.50, 0.75, 1.25 g.L− 1) over a 96 hour period to determine the LC50. In another experiment, five groups of ten animals were separated as follows: four groups for evaluation of the chronic effect of 0.45 g.L− 1 of metformin hydrochloride (15, 30, 45 and 60 days) and, a negative control group (NC). The antioxidant system and the tissue damages of the muscle samples and, the mutagenicity in the blood samples were evaluated. The presence of oxidative stress and mutagenicity, together with the activation of the antioxidant system, can be visualized up to 30 days of treatment, with intense tissue damages in 60 days and the emergence of apoptotic cells, which is evidence of the toxic potential of this drug to non-target aquatic populations.