Insulin- and Lipopolysaccharide-Mediated Signaling in Adipose Tissue Macrophages Regulates Postprandial Glycemia through Akt-mTOR Activation

Toda, Gotaro; Soeda, Kotaro; Okazaki, Yukiko; Kobayashi, Naoki; Masuda, Yukari; Arakawa, Naoko; Suwanai, Hirotsugu; Masamoto, Yosuke; Izumida, Yoshihiko; Kamei, Nozomu; Sasako, Takayoshi; Suzuki, Ryo; Kubota, Tetsuya; Kubota, Naoto; Kurokawa, Mineo; Tobe, Kazuyuki; Noda, Tetsuo; Honda, Kenya; Accili, Domenico; Yamauchi, Toshimasa; Kadowaki, Takashi; Ueki, Kohjiro

doi:10.1016/j.molcel.2020.04.033

Cited by 41 publications

(37 citation statements)

References 39 publications

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“…Lu et al have identified artemether as an activator of browning and thermogenesis in vitro, which significantly enhances the metabolism of mice, as indicated by the insulin tolerance test (ITT) and glucose tolerance test (GTT) results (Lu et al, 2016). To further evaluate the pharmacological potential, Lu et al found that artemether and other artemisinin derivatives induce C3H10T1/2 cell browning by activating the p38 mitogen-activated protein kinase (MAPK)/activating transcription factor-2 (ATF2) axis and deactivating the Akt/ mTOR pathway, which has suggested to be involved in various anabolic and catabolic processes (Cai et al, 2016;Lu et al, 2016;Fischer et al, 2020;Toda et al, 2020). Moreover, onestep qPCR suggested that the relative mRNA levels of browningrelated genes, such as PR domain containing 16 (PRDM16), uncoupling protein 1 (UCP1) and peroxisome proliferatoractivated receptor γ coactivator-1α (PGC-1α), were elevated after treatment with artemether, indicating that the increased thermogenesis in brown fat may also cause weight loss and enhance the metabolism in artemether-treated mice (Lu et al, 2016).…”

Section: Activation Of Brown Fat and Browning Of White Fatmentioning

confidence: 99%

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus

et al. 2020

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Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a global public health problem. Studies on T2DM prevention and treatment mostly focus on discovering therapeutic drugs. Artemisinin and its derivatives were originally used as antimalarial treatments. In recent years, the roles of artemisinins in T2DM have attracted much attention. Artemisinin treatments not only attenuate insulin resistance and restore islet ß-cell function in T2DM but also have potential therapeutic effects on diabetic complications, including diabetic kidney disease, cognitive impairment, diabetic retinopathy, and diabetic cardiovascular disease. Many in vitro and in vivo experiments have confirmed the therapeutic utility of artemisinin and its derivatives on T2DM, but no article has systematically demonstrated the specific role artemisinin plays in the treatment of T2DM. This review summarizes the potential therapeutic effects and mechanism of artemisinin and its derivatives in T2DM and associated complications, providing a reference for subsequent related research.

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Section: Activation Of Brown Fat and Browning Of White Fatmentioning

confidence: 99%

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus

et al. 2020

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“…In this issue of Molecular Cell, Toda et al (2020) show that postprandial elevation of LPS and insulin induce the production of IL-10 by adipose tissue macrophages. Hepatic gluconeogenesis is then inhibited synergistically by insulin and IL-10 to facilitate glucose clearance.…”

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confidence: 94%

“…In light of the vast complexity of the immuno-metabolism network, which so far has been shown to be highly dependent on experimental conditions, it is evident that rigorous analysis of macrophage biology is required to understand the influence of nutrition on the immune system. In this issue of Molecular Cell, Toda et al (2020) demonstrate the direct involvement of ATMs in regulating postprandial hepatic gluconeogenesis through interleukin-10 (IL-10).…”

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confidence: 99%

“…Although some studies have suggested that IL-10 might promote an anti-inflam-matory milieu, Toda et al (2020) add another layer of complexity to IL-10's role in the regulation of glucose homeostasis in the physiological state. Rahjbandari and colleagues described IL-10 as an important player in the maintenance of body weight, by inhibition of energy expenditure and beiging in mice (Rajbhandari et al, 2018).…”

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Fed Macrophages Hit the Liver’s Sweet Spot with IL-10

Sulen

Aouadi

2020

Molecular Cell

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“…In obese humans, IL10 expression in WAT was inversely associated with insulin resistance (Mclaughlin et al, 2014). Interesting, adipocytes are able to modulate immune responses in the spleen, including IL10 production (Vielma et al, 2013;Toda et al, 2020). Moreover, WAT depots also represent an abundant source of IL10 in the context of viral infections (Garcia-Valtanen et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The Vagus Nerve and Spleen: Influence on White Adipose Mass and Histology of Obese and Non-obese Rats

et al. 2021

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The vagus nerve (VN) and spleen represent a complex interface between neural and immunological functions, affecting both energy metabolism and white adipose tissue (WAT) content. Here, we evaluated whether vagal and splenic axis participates in WAT mass regulation in obese and non-obese male Wistar rats. High doses of monosodium glutamate (M; 4 g/Kg) were administered during the neonatal period to induce hypothalamic lesion and obesity (M-Obese rats). Non-obese or Control (CTL) rats received equimolar saline. At 60 days of life, M-Obese and CTL rats were randomly distributed into experimental subgroups according to the following surgical procedures: sham, subdiaphragmatic vagotomy (SV), splenectomy (SPL), and SV + SPL (n = 11 rats/group). At 150 days of life and after 12 h of fasting, rats were euthanized, blood was collected, and the plasma levels of glucose, triglycerides, cholesterol, insulin, and interleukin 10 (IL10) were analyzed. The visceral and subcutaneous WAT depots were excised, weighed, and histologically evaluated for number and size of adipocytes as well as IL10 protein expression. M-Obese rats showed higher adiposity, hyperinsulinemia, hypertriglyceridemia, and insulin resistance when compared with CTL groups (p < 0.05). In CTL and M-Obese rats, SV reduced body weight gain and triglycerides levels, diminishing adipocyte size without changes in IL10 expression in WAT (p< 0.05). The SV procedure resulted in high IL10 plasma levels in CTL rats, but not in the M-Obese group. The splenectomy prevented the SV anti-adiposity effects, as well as blocked the elevation of IL10 levels in plasma of CTL rats. In contrast, neither SV nor SPL surgeries modified the plasma levels of IL10 and IL10 protein expression in WAT from M-Obese rats. In conclusion, vagotomy promotes body weight and adiposity reduction, elevating IL10 plasma levels in non-obese animals, in a spleen-dependent manner. Under hypothalamic obesity conditions, VN ablation also reduces body weight gain and adiposity, improving insulin sensitivity without changes in IL10 protein expression in WAT or IL10 plasma levels, in a spleen-independent manner. Our findings indicate that the vagal-spleen axis influence the WAT mass in a health state, while this mechanism seems to be disturbed in hypothalamic obese animals.

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Insulin- and Lipopolysaccharide-Mediated Signaling in Adipose Tissue Macrophages Regulates Postprandial Glycemia through Akt-mTOR Activation

Cited by 41 publications

References 39 publications

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus

Fed Macrophages Hit the Liver’s Sweet Spot with IL-10

The Vagus Nerve and Spleen: Influence on White Adipose Mass and Histology of Obese and Non-obese Rats

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