RESUMO
This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX-D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund's Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17ß-estradiol (28 µg/kg/day) or placebo for 21 days (D10-D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-É levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-É levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-É levels in the animals submitted to both models, which was partially reverted by HRT.
RESUMO
Chronic stress is a common condition affecting health, often associated with unhealthy eating habits. Transcranial direct current stimulation (tDCS) has been proposed to address these issues. Thus, this research investigated the effects of tDCS on biometric, behavioral, and neurochemical parameters in chronically stressed rats fed a hyper-palatable cafeteria diet (CAFD). The study lasted 8 weeks, with CAFD exposure and/or chronic restraint stress model (CRS - 1 h/day, 5 days/week, for 7 weeks) started concurrently. tDCS or sham sessions were applied between days 42 and 49 (0.5 mA, 20 min/day). CAFD increased body weight, caloric consumption, adiposity, and liver weight. It also altered central parameters, reducing anxiety and cortical levels of IL-10 and BDNF. In turn, the CRS resulted in increased adrenals in rats with standard diet (SD), and anxiety-like and anhedonic behaviors in rats with CAFD. tDCS provided neurochemical shifts in CAFD-fed stressed rats increasing central levels of TNF-α and IL-10, while in stressed rats SD-fed induced a decrease in the adrenals weight, relative visceral adiposity, and serum NPY levels. These data demonstrated the anxiolytic effect of CAFD and anxiogenic effect of stress in CAFD-fed animals. In addition, tDCS promoted state-dependent effects on neuroinflammatory and behavioral parameters in rats chronically exposed to stress and a hyper-palatable diet. These findings provide primary evidence for additional mechanistic and preclinical studies of the tDCS technique for stress-related eating disorders, envisioning clinical applicability.
Assuntos
Estimulação Transcraniana por Corrente Contínua , Ratos , Animais , Interleucina-10 , Dieta , Obesidade , Ansiedade/terapiaRESUMO
OBJECTIVES: No specific therapy is available for metabolic dysfunction-associated fatty liver disease. We investigated nicotinamide riboside (NR) and dietary restriction (DR) effects in liver lipids, inflammation, histology, intestinal permeability, and gut microbiota in a cafeteria diet (CAFD)-induced obesity model. METHODS: Adult male Wistar rats were randomly assigned to standard diet (SD) or CAFD. After 6 wk, they were subdivided into six groups-SD + vehicle (Veh) (distilled water), SD + NR (400 mg/kg), DR + Veh, DR + NR, CAFD + Veh, and CAFD + NR-for 4 wk more until euthanasia. RESULTS: CAFD increased the hepatic content of lipids, triacylglycerols, and total cholesterol and promoted hepatomegaly, steatosis, steatohepatitis, and liver fibrosis. DR intervention successfully delayed the onset of CAFD-induced liver abnormalities except for steatosis and fibrosis. CAFD suppressed Sirt1 expression in the liver and DR increased Sirt3 expression. CAFD did not affect hepatic inflammatory genes but DR enhanced Il10 expression while decreasing Il1ß expression. CAFD reduced Firmicutes and increased Bacteroidetes and Cyanobacteria, with no changes in intestinal permeability. Gut microbiota patterns in animals exposed to DR were similar to those of animals in SD. NR, specifically in CAFD, reduced hepatic triacylglycerols and total cholesterol deposition and collagen fiber accumulation in the liver and limited the colonization of CAFD-induced Cyanobacteria. NR combined with DR decreased the liver's relative weight and Tnfα expression and suppressed Sirt1 and Sirt3 hepatic expression. CONCLUSIONS: This study suggests that NR can be a potential adjuvant to metabolic dysfunction-associated fatty liver disease therapy, encouraging further research in this field.
Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Sirtuína 3 , Ratos , Masculino , Animais , Sirtuína 1/metabolismo , Sirtuína 3/metabolismo , Sirtuína 3/farmacologia , Ratos Wistar , Obesidade/metabolismo , Fígado/metabolismo , Dieta , Hepatopatia Gordurosa não Alcoólica/metabolismo , Colesterol , Lipídeos , Triglicerídeos/metabolismo , Dieta HiperlipídicaRESUMO
Obesity treatments, such as calorie restriction (CR), eventually lead to muscle wasting and higher rates of neuroinflammation, whereas hypothalamic inflammatory conditions impair body weight (BW) control. Nicotinamide riboside (NR) has been proposed against obesity but with little evidence on skeletal muscle tissue (SMT) and neuroinflammation. Therefore, we aimed to investigate the effects of CR on SMT and on hypothalamic inflammatory biomarkers in obese adult male Wistar rats, and whether NR supplementation alone or in combination with CR affects these parameters. Obesity was induced in rats through a cafeteria diet for 6 weeks. After that, a group of obese rats was exposed to CR, associated or not associated with NR supplementation (400 mg/kg), for another 4 weeks. As a result, obese rats, with or without CR, presented lower relative weight of SMT when compared with eutrophic rats. Rats under CR presented lower absolute SMT weight compared with obese and eutrophic rats, in addition to presenting elevated hypothalamic levels of TNF-α. NR supplementation, in all groups, enhanced weight loss and increased relative weight of the SMT. Furthermore, in animals under CR, NR reversed increases TNF-α levels in the hypothalamus. In this study, these data, although succinct, are the first to evidence the effects of NR on SMT and neuroinflammation when associated with CR, especially in obesity conditions. Therefore, this provides preliminary support for future studies in this investigative field. Furthermore, NR emerges as a potential adjuvant for preventing muscle mass loss in the weight loss processes.