Mitofusin-2 induced by exercise modifies lipid droplet-mitochondria communication, promoting fatty acid oxidation in male mice with NAFLD

Background and aim: The excessive accumulation of lipid droplets (LDs) is a defining characteristic of nonalcoholic fatty liver disease (NAFLD). The interaction between LDs and mitochondria is functionally important for lipid metabolism homeostasis. Exercise improves NAFLD, but it is not known if it has an effect on hepatic LD-mitochondria interactions. Here, we investigated the influence of exercise on LD-mitochondria interactions and its significance in the context of NAFLD. Approach and results: Mice were fed high-fat diet (HFD) or HFD-0.1 % methionine and choline-deficient diet (MCD) to emulate simple hepatic steatosis or non-alcoholic steatohepatitis, respectively. In both models, aerobic exercise decreased the size of LDs bound to mitochondria and the number of LD-mitochondria contacts. Analysis showed that the effects of exercise on HOMA-IR and liver triglyceride levels were independent of changes in body weight, and a positive correlation was observed between the number of LD-mitochondria contacts and NAFLD severity and with the lipid droplet size bound to mitochondria. Cellular fractionation studies revealed that ATP-coupled respiration and fatty acid oxidation (FAO) were greater in hepatic peridroplet mitochondria (PDM) from HFD-fed exercised mice than from equivalent sedentary mice. Finally, exercise increased FAO and mitofusin-2 abundance exclusively in PDM through a mechanism involving the curvature of mitochondrial membranes and the abundance of saturated lipids. Accordingly, hepatic mitofusin-2 ablation prevented exercise-induced FAO in PDM. Conclusions: This study demonstrates that aerobic exercise has beneficial effects in murine NAFLD models by lessening the interactions between hepatic LDs and mitochondria, and by decreasing LD size, correlating with a reduced severity of NAFLD. Additionally, aerobic exercise increases FAO in PDM and this process is reliant on Mfn-2 enrichment, which modifies LD-mitochondria communication

Diabetes-associated changes in the fetal insulin/insulin-like growth factor system are organ specific in rats

Background: Diabetes in pregnancy affects fetal growth and development. The insulin/insulin-like growth factors (IGF) system comprising insulin, IGF, their receptors, and binding proteins, has been implicated in fetal growth regulation. This study tested the hypothesis that maternal diabetes alters the fetal insulin/IGF system in a tissue-specific manner. Methods: Wistar rats were rendered diabetic by neonatal administration of streptozotocin and mated with control rats. At day 21 of gestation, the weights of fetuses, placentas, and fetal organs (heart, lung, liver, stomach, intestine, and pancreas) were determined. Maternal and fetal plasma concentrations of insulin, IGF1, and IGF2 were measured by ELISA, and expression of IGF1, IGF2, IGF1R, IGF2R, IR, IGFBP1, BP2, and BP3 in placenta and fetal organs by qPCR. Results: The well-known increase in fetal growth in this model of mild diabetes is accompanied by elevated insulin and IGF1 levels and alterations of the insulin/IGF system in the fetus and the placenta. These alterations were organ and gene specific. The insulin/IGF system was generally upregulated, especially in the fetal heart, while it was downregulated in fetal lung. Conclusion: In our model of mild diabetes, the effect of maternal diabetes on fetal weight and fetal insulin/IGF system expression is organ specific with highly sensitive organs such as lung and heart, and organs that were less affected, such as stomach.Fil: White, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Mazzucco, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Gauster, Martin. Medical University of Graz. Institute of Cell Biology, Histology and Embryology; AustriaFil: Desoye, Gernot. Medical University of Graz. Department of Obstetrics and Gynaecology; AustriaFil: Hiden, Ursula. Medical University of Graz. Department of Obstetrics and Gynaecology; Austri

Comprovação do efeito antioxidante de plantas medicinais utilizadas no tratamento do Diabetes mellitus em animais: artigo de atualização Evidence of the antioxidant effect of medicinal plants used in the treatment of Diabetes mellitus in animals: an update

Diabetes mellitus (DM) é uma síndrome de etiologia múltipla caracterizada por hiperglicemia crônica. Esta hiperglicemia induz o aumento na produção de espécies reativas de oxigênio (ERO) e diminuição das defesas antioxidantes. Devido às complicações causadas pelo diabete, muitos indivíduos optam por terapias alternativas à base de plantas medicinais para amenizar seus efeitos. Sendo assim, nesta revisão de literatura, foram analisados e descritos diversos trabalhos experimentais com a utilização de animais diabéticos para comprovar os efeitos antioxidantes de algumas dessas plantas e verificar se os títulos e resumos disponibilizados nos artigos são compatíveis aos objetivos de nossa busca.<br>Diabetes mellitus (DM) is a syndrome of multiple etiology characterized by chronic hyperglycemia. This hyperglycemia induces increased production of reactive oxygen species (ROS) and decreased antioxidant defenses. Due to complications caused by diabetes, a large number of people have chosen medicinal plant-based alternative therapies to alleviate its effects. Thus, in this literature review, several experimental studies with the use of diabetic animals were analyzed to demonstrate the antioxidant effects of these plants and to verify if the titles and abstracts provided in the papers are compatible with the aims of our search