Prenatal caloric restriction adjusts the energy homeostasis and behavior in response to acute and chronic variations in food availability in adulthood.

Fetal metabolic programming produced by unfavorable prenatal nutritional conditions leads to the development of a disorder called "thrifty phenotype", which is associated with pathologies such as diabetes and obesity in adulthood. However, from an ecophysiological approach, few studies have addressed the development of thrifty phenotypes in terms of energy. This might represent an adaptive advantage against caloric deficiency conditions extending into adulthood. The objective of this study is to investigate the potential adaptive value of the thrifty phenotype expression through prenatal programming in a rodent model experiencing varying dietary conditions in different temporal contexts. To fill this gap, adult males of Mus musculus (BALB/C) from two maternal pregnancy groups were analyzed: control (ad libitum feeding) and caloric restriction from day 10 of gestation (70% restriction). Adult offspring of these groups were split further for two experiments: acute food deprivation and chronic caloric restriction at 60%. The acute food deprivation was performed for 24, 48 or 72 h while the caloric restriction regime was sustained for 20 days. For each experiment, morphological variables, such as body and organ mass, and gene expression related to lipid and carbohydrate metabolism from the liver and brain, were evaluated. In chronic caloric restriction, behavioral tests (open-field test and home-cage behavior) were performed. Our results indicate that under acute deprivation, the liver mass and triglyceride content remained unchanged in individuals subjected to prenatal restriction, in contrast to the reduction experienced by the control group. The latter is associated with the expression of the key genes involved in energy homeostasis (Pepck, Pparα/Pparγ), indicating a differential use of nutritional resources. In addition, thrifty animals, subjected to chronic caloric restriction, showed a severe reduction in locomotor and gluconeogenic activity, which is consistent with the regulatory role of Sirt1 and its downstream targets Mao and Pepck. Our results reveal that prenatal caloric restriction translates into a sparing metabolism in response to acute and chronic lack of food in adulthood.

Hyperbaric oxygen treatment increases intestinal stem cell proliferation through the mTORC1/S6K1 signaling pathway in Mus musculus.

BACKGROUND: Hyperbaric oxygen treatment (HBOT) has been reported to modulate the proliferation of neural and mesenchymal stem cell populations, but the molecular mechanisms underlying these effects are not completely understood. In this study, we aimed to assess HBOT somatic stem cell modulation by evaluating the role of the mTOR complex 1 (mTORC1), a key regulator of cell metabolism whose activity is modified depending on oxygen levels, as a potential mediator of HBOT in murine intestinal stem cells (ISCs). RESULTS: We discovered that acute HBOT synchronously increases the proliferation of ISCs without affecting the animal's oxidative metabolism through activation of the mTORC1/S6K1 axis. mTORC1 inhibition by rapamycin administration for 20 days also increases ISCs proliferation, generating a paradoxical response in mice intestines, and has been proposed to mimic a partial starvation state. Interestingly, the combination of HBOT and rapamycin does not have a synergic effect, possibly due to their differential impact on the mTORC1/S6K1 axis. CONCLUSIONS: HBOT can induce an increase in ISCs proliferation along with other cell populations within the crypt through mTORC1/S6K1 modulation without altering the oxidative metabolism of the animal's small intestine. These results shed light on the molecular mechanisms underlying HBOT therapeutic action, laying the groundwork for future studies.