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.

Efficacy of stem cell secretome loaded in hyaluronate sponge for topical treatment of psoriasis.

Psoriasis vulgaris is an inflammatory disease characterized by distinctive skin lesions and dysregulated angiogenesis. Recent research uses stem cell secretion products (CM); a set of bioactive factors with therapeutic properties that regulate several cellular processes, including tissue repair and angiogenesis. The aim of this work was to evaluate the effect of CM of Wharton's gelatin MSC (hWJCM) in a treatment based on the bioactivation of a hyaluronic acid matrix (HA hWJCM) in a psoriasiform-like dermatitis (PD) mouse model. A preclinical study was conducted on PD mice. The effect of hWJCM, Clobetasol (Clob) gold standard, HA Ctrl, and HA hWJCM was tested topically evaluating severity of PD, mice weight as well as skin, liver, and spleen appearance. Treatment with either hWJCM, HA Ctrl or HA hWJCM, resulted in significant improvement of the PD phenotype. Moreover, treatment with HA hWJCM reduced the Psoriasis Area Severity Index (PASI), aberrant angiogenesis, and discomfort associated with the disease, leading to total recovery of body weight. We suggest that the topical application of HA hWJCM can be an effective noninvasive therapeutic solution for psoriasis, in addition to other skin diseases, laying the groundwork for future studies in human patients.

Perinatal Food Deprivation Modifies the Caloric Restriction Response in Adult Mice Through Sirt1.

Variations in the availability of nutritional resources in animals can trigger reversible adjustments, which in the short term are manifested as behavioral and physiological changes. Several of these responses are mediated by Sirt1, which acts as an energy status sensor governing a global genetic program to cope with changes in nutritional status. Growing evidence suggests a key role of the response of the perinatal environment to caloric restriction in the setup of physiological responses in adulthood. The existence of adaptive predictive responses has been proposed, which suggests that early nutrition could establish metabolic capacities suitable for future food-scarce environments. We evaluated how perinatal food deprivation and maternal gestational weight gain impact the transcriptional, physiological, and behavioral responses in mice, when acclimated to caloric restriction in adulthood. Our results show a strong predictive capacity of maternal weight and gestational weight gain, in the expression of Sirt1 and its downstream targets in the brain and liver, mitochondrial enzymatic activity in skeletal muscle, and exploratory behavior in offspring. We also observed differential responses of both lactation and gestational food restriction on gene expression, thermogenesis, organ masses, and behavior, in response to adult caloric restriction. We conclude that the early nutritional state could determine the magnitude of responses to food scarcity later in adulthood, mediated by the pivotal metabolic sensor Sirt1. Our results suggest that maternal gestational weight gain could be an important life history trait and could be used to predict features that improve the invasive capacity or adjustment to seasonal food scarcity of the offspring.