👤 Rodolfo Marinho

Paternal environmental factors before conception and during sperm development may influence the offspring's health later in life. This study aimed to investigate whether paternal exposure to anabolic-androgenic steroids (AAS) before conception predisposes mouse offspring to autism spectrum disorder (ASD)-like behavior. For this purpose, male Swiss mice were randomly divided into two groups: the control group received peanut oil, while the treated group was administered testosterone propionate (7.5 mg/kg, s.c.) twice a week for five weeks. After this period, these males were mated, and their offspring underwent a behavioral test battery at 70 days of age, including the open field test, object recognition task, three-chamber social approach test, and light-dark box test. At the end of the experiment, the hippocampus was dissected for RNA analysis. Our results indicate that paternal AAS treatment induces long-lasting behavioral alterations in both female and male offspring, including increased anxiety-like behavior, impaired memory, and deficits in social interaction. Additionally, a strong effect of paternal AAS treatment during preconception period was verified in Gad1, Gabra2 and Bdnf expression. These findings suggest that paternal AAS exposure may program neurodevelopmental vulnerabilities in offspring, contributing to ASD-like phenotypes. Show less

The hypothalamic neuropeptides linked to appetite and satiety were investigated in obese mice treated with cotadutide (a dual receptor agonist of glucagon-like peptide 1 (GLP-1R)/Glucagon (GCGR)). Twelve-week-old male C57BL/6 mice were fed a control diet (C group, n = 20) or a high-fat diet (HF group, n = 20) for ten weeks. Each group was further divided, adding cotadutide treatment and forming groups C, CC, HF, and HFC for four additional weeks. The hypothalamic arcuate neurons were labeled by immunofluorescence, and protein expressions (Western blotting) for neuropeptide Y (NPY), proopiomelanocortin (POMC), agouti-related protein (AgRP), and cocaine- and amphetamine-regulated transcript (CART). Cotadutide enhanced POMC and CART neuropeptides and depressed NPY and AGRP neuropeptides. In addition, gene expressions (RT-qPCR) determined that Lepr (leptin receptor) and Calcr (calcitonin receptor) were diminished in HF compared to C but enhanced in CC compared to C and HFC compared to HF. Besides, Socs3 (suppressor of cytokine signaling 3) was decreased in HFC compared to HF, while Sst (somatostatin) was higher in HFC compared to HF; Tac1 (tachykinin 1) and Mc4r (melanocortin-4-receptor) were lower in HF compared to C but increased in HFC compared to HF. Also, Glp1r and Gcgr were higher in HFC compared to HF. In conclusion, the findings are compelling, demonstrating the effects of cotadutide on hypothalamic neuropeptides and hormone receptors of obese mice. Cotadutide modulates energy balance through the gut-brain axis and its associated signaling pathways. The study provides insights into the mechanisms underlying cotadutide's anti-obesity effects and its possible implications for obesity treatment. Show less

Arterial hypertension (AH) is implicated in vascular health and contributes significantly to cardiovascular morbidity and mortality. In addition to the contribution of usual risk factors for AH, elucidating the influence of genetic factors is a promising area of investigation. Therefore, we evaluated the association between AH and cardiovascular risk factors (CVRFs) and genetic polymorphisms in communities in Southeast Brazil. A total of 515 adults aged 18-91 years, who were cross-sectionally assessed between 2015-2016, were included. Demographic, clinical, behavioral, anthropometric characteristics, and laboratory parameters and 12 single nucleotide polymorphisms in seven candidate genes involved in cardiovascular risk ( There was a significant association between age >60 years (odds ratio [OR] =6.74), alcohol dependence (OR=3.84), smoking (OR=1.74), overweight (OR=1.74), high plasma triglyceride (TG) levels (OR=1.98) and low high-density lipoprotein (HDL-c) (OR=6.22), diabetes (OR=3.68), and insulin resistance (OR=2.40) and AH. A significant association was observed between rs4721 in The interaction of the T allele of the rs4721 polymorphism in Show less

Insulin plays an important role in the control of hepatic glucose production. Insulin resistant states are commonly associated with excessive hepatic glucose production, which contributes to both fasting hyperglycaemia and exaggerated postprandial hyperglycaemia. In this regard, increased activity of phosphatases may contribute to the dysregulation of gluconeogenesis. Mitogen-activated protein kinase phosphatase-3 (MKP-3) is a key protein involved in the control of gluconeogenesis. MKP-3-mediated dephosphorylation activates FoxO1 (a member of the forkhead family of transcription factors) and subsequently promotes its nuclear translocation and binding to the promoters of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). In this study, we investigated the effects of exercise training on the expression of MKP-3 and its interaction with FoxO1 in the livers of obese animals. We found that exercised obese mice had a lower expression of MKP-3 and FoxO1/MKP-3 association in the liver. Further, the exercise training decreased FoxO1 phosphorylation and protein levels of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and gluconeogenic enzymes (PEPCK and G6Pase). These molecular results were accompanied by physiological changes, including increased insulin sensitivity and reduced hyperglycaemia, which were not caused by reductions in total body mass. Similar results were also observed with oligonucleotide antisense (ASO) treatment. However, our results showed that only exercise training could reduce an obesity-induced increase in HNF-4α protein levels while ASO treatment alone had no effect. These findings could explain, at least in part, why additive effects of exercise training treatment and ASO treatment were not observed. Finally, the suppressive effects of exercise training on MKP-3 protein levels appear to be related, at least in part, to the reduced phosphorylation of Extracellular signal-regulated kinases (ERK) in the livers of obese mice. Show less