Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with cardiometabolic risk. Although studies have shown that estradiol positively contributes to energy metabolism via estrogen receptor alpha (ERα), its role specifically in the liver is not defined. Therefore, this study aimed to evaluate the effects of ERα overexpression, specifically in the liver in mice fed a high-fat diet (HFD). Methods: Male C57BL/6J mice were divided into four groups, vehicle fed with regular chow (RC) (RC-Vehicle); vehicle fed an HFD (HFD-Vehicle); AAV-treated fed with RC (RC-AAV); and AAV-treated fed an HFD (HFD-AAV), for 6 weeks (8–10 mice per group). AAV was administered intravenously to induce ERα overexpression. Results: We demonstrate that overexpression of ERα in RC-fed mice reduces body fat (28%). These mice show increased oxygen consumption in cultured primary hepatocytes, both in basal (19%) and maximal respiration (34%). In HFD-fed mice, we showed a decrease in hepatic TAG content (43%) associated with improved hepatic insulin sensitivity (145%). Conclusions: From this perspective, our results prove that hepatic ERα signaling is responsible for some of the metabolic protective effects of estrogen in mice. Overexpression of ERα improves hepatocyte mitochondrial function, consequently reducing hepatic lipid accumulation and protecting animals from hepatic steatosis and hepatic insulin resistance. Further investigations will be needed to determine the exact molecular mechanism by which ERα improves hepatic metabolic health.
Menopause is characterized by a reduction in sex hormones in women and is associated with metabolic changes, including fatty liver and insulin resistance. Lifestyle changes, including a balanced diet and physical exercise, are necessary to prevent these undesirable changes. Strength training (ST) has been widely used because of the muscle and metabolic benefits it provides. Our study aims to evaluate the effects of ST on hepatic steatosis and insulin resistance in ovariectomized mice fed a high-fat diet (HFD) divided into four groups as follows: simulated sedentary surgery (SHAM-SED), trained simulated surgery (SHAM-EXE), sedentary ovariectomy (OVX-SED), and trained ovariectomy (OVX-EXE). They were fed an HFD for 9 weeks. ST was performed thrice a week. ST efficiently reduced body weight and fat percentage and increased lean mass in OVX mice. Furthermore, ST reduced the accumulation of ectopic hepatic lipids, increased AMPK phosphorylation, and inhibited the de novo lipogenesis pathway. OVX-EXE mice also showed a better glycemic profile, associated with greater insulin sensitivity identified by the euglycemic–hyperinsulinemic clamp, and reduced markers of hepatic oxidative stress compared with sedentary animals. Our data support the idea that ST can be indicated as a non-pharmacological treatment approach to mitigate metabolic changes resulting from menopause.
In recent decades, clinical and experimental studies have revealed that estradiol contributes enormously to glycemic homeostasis. However, the same consensus does not exist in women during menopause who undergo replacement with progesterone or conjugated estradiol and progesterone. Since most hormone replacement treatments in menopausal women are performed with estradiol (E2) and progesterone (P4) combined, this work aimed to investigate the effects of progesterone on energy metabolism and insulin resistance in an experimental model of menopause (ovariectomized female mice—OVX mice) fed a high-fat diet (HFD). OVX mice were treated with E2 or P4 (or both combined). OVX mice treated with E2 alone or combined with P4 displayed reduced body weight after six weeks of HFD feeding compared to OVX mice and OVX mice treated with P4 alone. These data were associated with improved glucose tolerance and insulin sensitivity in OVX mice treated with E2 (alone or combined with P4) compared to OVX and P4-treated mice. Additionally, E2 treatment (alone or combined with P4) reduced both hepatic and muscle triglyceride content compared with OVX control mice and OVX + P4 mice. There were no differences between groups regarding hepatic enzymes in plasma and inflammatory markers. Therefore, our results revealed that progesterone replacement alone does not seem to influence glucose homeostasis and ectopic lipid accumulation in OVX mice. These results will help expand knowledge about hormone replacement in postmenopausal women associated with metabolic syndrome and non-alcoholic fatty liver disease.
19 December 2024 in Proceedings of the National Academy of Sciences
Growth hormone (GH) has several metabolic effects, including a profound impact on glucose homeostasis. For example, GH oversecretion induces insulin resistance and increases the risk of developing diabetes mellitus. Here, we show that GH receptor (GHR) ablation in vesicular glutamate transporter 2 (VGLUT2)-expressing cells, which comprise a subgroup of glutamatergic neurons, led to a slight decrease in lean body mass without inducing changes in body adiposity. VGLUT2 ∆GHR mice exhibited reduced glycemia and improved glucose tolerance and insulin sensitivity. Among different glutamatergic neuronal populations, we found that GHR inactivation in Sim1-expressing cells recapitulated the phenotype observed in VGLUT2 ∆GHR mice. Furthermore, Sim1 ∆GHR mice exhibited reduced endogenous glucose production and improved hepatic insulin sensitivity without alterations in whole-body or muscle glucose uptake. Sim1 ∆GHR mice were protected against acute but not chronic diabetogenic effects of exogenous GH administration. Pharmacological activation of ATP-sensitive potassium channels in the brain normalized blood glucose levels in Sim1 ∆GHR mice. In conclusion, the absence of GHR signaling in VGLUT2/Sim1-expressing cells causes a persistent reduction in glycemia and improves hepatic insulin sensitivity. Central glucose-sensing mechanisms are likely involved in the reduced glycemia exhibited by Sim1 ∆GHR mice. The current findings uncover a mechanism involved in the effects of GHR signaling in regulating glucose homeostasis.
O presente estudo descritivo tem o objetivo de realizar um levantamento bibliográfico dos principais estudos acerca do treinamento intervalado de alta intensidade (HIIT) e do estresse oxidativo, possibilitando a sistematização das informações acerca dos seus principais conceitos. Ainda há muitas controvérsias sobre as duas temáticas e a relação entre elas. Depois da seleção dos artigos, foram definidas categorias para descrever os conceitos que norteiam as temáticas apresentadas. Sendo descrito os principais conceitos de HIIT, radicais livres, estresse oxidativo, espécies reativas de oxigênio, sistemas de defesa antioxidante endógenos e exógenos e a relação entre o treinamento intervalado e o estresse oxidativo. Assim, o HIIT pode contribuir de maneira dual sobre o organismo, entre os seus efeitos deletérios são evidenciados o aumento do estresse oxidativo, diminuição do desempenho e a fadiga. Todavia, alguns estudos demonstram que os ajustes fisiológicos do HIIT proporcionam efeitos benéficos na saúde, principalmente na capacidade oxidante, sendo necessário estudos mais aprofundados para identificar outros eventos intracelulares que o HIIT pode ocasionar relacionando ao estresse oxidativo.
17 September 2020 in Research, Society and Development
Introdução: O envelhecimento é um processo fisiológico que acontece em todos os organismos vivos com perda das funções celulares, podendo consequentemente diminui as chances de sobrevivência. A atividade física pode não apresentar uma “fonte da juventude”, mas a maioria das evidências mostra que essa praticada de forma regular retarda o declínio no processo relacionado ao envelhecimento. Objetivo: identificar o nível de condicionamento físico, nos idosos que frequentam regularmente um projeto social situado na Zona Sul da cidade de Aracaju – SE. Métodos: Foi realizada uma pesquisa de campo de caráter descritivo. A amostra foi constituída por idosos do projeto Conte Conosco da cidade de Aracaju-SE. Os dados foram analisados e classificados através do método estatístico Quartil por meio Excel 2010. Para avaliar o condicionamento físico do idoso, foi utilizado o protocolo do Grupo de Desenvolvimento Humano Latino-Americano Para a Maturidade-GDLAM. Resultados: De acordo com os resultados obtidos, a maioria foi classificada como insuficiente o que pode ser explicado pelas características das atividades físicas proposta para esses idosos. Conclusão: Conclui-se que, mesmo praticando exercícios físicos regularmente, os idosos que participaram da amostragem não apresentaram condicionamento físico satisfatório.