Oestrogen receptor α in T cells controls the T cell immune profile and glucose metabolism in mouse models of gestational diabetes mellitus

Tanaka, Tomoko; Wada, Tsutomu; Uno, Kimie; Ogihara, Saki; Ie, Hiromi; Okekawa, Akira; Ishikawa, Akari; Ito, Tetsuo; Miyazawa, Yuichiro; Sameshima, Azusa; Onogi, Yasuhiro; Tsuneki, Hiroshi; Sasahara, Masakiyo; Nakashima, Akitoshi; Saito, Shigeru; Sasaoka, Toshiyasu

doi:10.1007/s00125-021-05447-x

Cited by 8 publications

(9 citation statements)

References 55 publications

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“…129 Therefore, studies have focused on glucose metabolism levels in DM. 130 The deposition of lipid significantly increases in DM patients, making them prone to the development of other diseases such as non-alcoholic fatty liver disease. 131 Enhancing lipid metabolism https://doi.org/10.2147/IJN.S350250…”

Section: Exosomes Glucose and Lipid Metabolismmentioning

confidence: 99%

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Ashrafizadeh¹,

Kumar²,

Aref³

et al. 2022

IJN

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Diabetes mellitus (DM) is among the chronic metabolic disorders that its incidence rate has shown an increase in developed and wealthy countries due to lifestyle and obesity. The treatment of DM has always been of interest, and significant effort has been made in this field. Exosomes belong to extracellular vesicles with nanosized features (30-150 nm) that are involved in cell-to-cell communication and preserving homeostasis. The function of exosomes is different based on their cargo, and they may contain lipids, proteins, and nucleic acids. The present review focuses on the application of exosomes in the treatment of DM; both glucose and lipid levels are significantly affected by exosomes, and these nanostructures enhance lipid metabolism and decrease its deposition. Furthermore, exosomes promote glucose metabolism and affect the level of glycolytic enzymes and glucose transporters in DM. Type I DM results from the destruction of β cells in the pancreas, and exosomes can be employed to ameliorate apoptosis and endoplasmic reticulum (ER) stress in these cells. The exosomes have dual functions in mediating insulin resistance/sensitivity, and M1 macrophage-derived exosomes inhibit insulin secretion. The exosomes may contain miRNAs, and by transferring among cells, they can regulate various molecular pathways such as AMPK, PI3K/Akt, and β-catenin to affect DM progression. Noteworthy, exosomes are present in different body fluids such as blood circulation, and they can be employed as biomarkers for the diagnosis of diabetic patients. Future studies should focus on engineering exosomes derived from sources such as mesenchymal stem cells to treat DM as a novel strategy.

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Section: Exosomes Glucose and Lipid Metabolismmentioning

confidence: 99%

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Ashrafizadeh¹,

Kumar²,

Aref³

et al. 2022

IJN

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“…GDM mouse model was established as previously described ( 65 ), and the experimental procedure is shown in Fig. 2A and fig.…”

Section: Methodsmentioning

confidence: 99%

Lachnospiraceae -derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus

Huang,

Chen,

Cui

et al. 2023

Sci. Adv.

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Inflammation-associated insulin resistance is a key trigger of gestational diabetes mellitus (GDM), but the underlying mechanisms and effective interventions remain unclear. Here, we report the association of placental inflammation (tumor necrosis factor–α) and abnormal maternal glucose metabolism in patients with GDM, and a high fermentable dietary fiber (HFDF; konjac ) could reduce GDM development through gut flora–short-chain fatty acid–placental inflammation axis in GDM mouse model. Mechanistically, HFDF increases abundances of Lachnospiraceae and butyrate, reduces placental-derived inflammation by enhancing gut barrier and inhibiting the transfer of bacterial-derived lipopolysaccharide, and ultimately resists high-fat diet–induced insulin resistance. Lachnospiraceae and butyrate have similar anti-GDM and anti–placental inflammation effects, and they can ameliorate placental function and pregnancy outcome effects probably by dampening placental immune dysfunction. These findings demonstrate the involvement of important placental inflammation–related mechanisms in the progression of GDM and the great potential of HFDFs to reduce susceptibility to GDM through gut-flora-placenta axis.

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“…The glucose tolerance test (GTT) was conducted by an intraperitoneal injection of glucose (2 g/kg body weight) after 6 h of fasting, and the insulin tolerance test (ITT) by an intraperitoneal injection of insulin (0.75 U/kg body weight) after 4 h of fasting, as previously described [ 29 ]. Each examination was performed on 17-week-old mice.…”

Section: Methodsmentioning

confidence: 99%

“…RNA extraction, reverse transcription, and real-time PCR using SYBR green were performed as previously described [ 29 , 30 ]. The relative expression of objective mRNA was calculated as a ratio to that of 18S ribosomal RNA.…”

Section: Methodsmentioning

confidence: 99%

“…Tissue was embedded in OCT compound (Sakura Finetek, Osaka, Japan), and 20-µm-thick cross-sections were obtained from the center of muscle tissue using a cryostat and stained with H&E. Photomicrographs were captured using BZX800 (Keyence, Osaka, Japan). The cross-sections of each adipocyte and myofiber were traced one by one, and the area of each traced region was analyzed, using ImageJ 1.45 s software (NIH) or the BZX800 system (Keyence), respectively [ 29 , 31 ]. The average size of adipocytes and myofiber was calculated by analyzing ~ 300 adipocytes or myofibers per mouse from the H&E-stained sections of eWAT or gastrocnemius muscle.…”

Section: Methodsmentioning

confidence: 99%

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A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice

et al. 2023

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Aim MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement. Materials and methods Male C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Results HFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes. Conclusions A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice.

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Oestrogen receptor α in T cells controls the T cell immune profile and glucose metabolism in mouse models of gestational diabetes mellitus

Cited by 8 publications

References 55 publications

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

Lachnospiraceae -derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus

A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice

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