The effect of mirabegron on energy expenditure and brown adipose tissue in healthy lean South <scp>Asian and Europid</scp> men

Nahon, Kimberly J.; Janssen, Laura G.M.; Mishre, Aashley S. D. Sardjoe; Bilsen, Manu P; Eijk, Jari A. van der; Botani, Kani; Overduin, Lisanne A.; Ruiz, Jonatan R.; Burakiewicz, Jedrzej; Dzyubachyk, Oleh; Webb, Andrew; Kan, H.; Berbée, Jimmy F.P.; Klinken, Jan-Bert van; Dijk, Ko Willems van; Weeghel, Michel van; Vaz, Frédéric M.; Coşkun, Tamer; Jazet, Ingrid M.; Kooijman, Sander; Martínez-Téllez, Borja; Boon, Mariëtte R.; Rensen, Patrick C.N.

doi:10.1111/dom.14120

Cited by 28 publications

(33 citation statements)

References 59 publications

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“…Ethnicity has been shown to affect the gut microbiome 55 but not BAT activity. 56,57 Although it is unlikely that ethnicity influenced our conclusions related to BAT activity, further investigation in an ethnically diverse group would be needed to demonstrate this definitively. Last, the human microbiota can be influenced by diet.…”

Section: Limitations Of the Studymentioning

confidence: 93%

Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota

Ahmed

Ong

Barra

et al. 2021

Cell Reports Medicine

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Section: Limitations Of the Studymentioning

confidence: 93%

Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota

Ahmed

Ong

Barra

et al. 2021

Cell Reports Medicine

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“…11,12 Mirabegron (YM1178) is a selective β₃-AR agonist approved for the treatment of overactive bladder. 13 Recently, treatment with mirabegron was observed to increase BAT activation 7,14 and energy expenditure, 15 and improve lipid profile 16 and glucose homeostasis. 17,18 However, whether mirabegron can decrease the levels of circulating inflammatory markers and ectopic lipid accumulation in diet-induced obesity (DIO) is still unclear.…”

Section: Introductionmentioning

confidence: 99%

The effects of mirabegron on obesity‐induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue

Silva

Calmasini

Alexandre

et al. 2021

Clin Exp Pharma Physio

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Mirabegron is a selective β₃-adrenergic receptors agonist, which has been recentlyshown to improve metabolic health in rodents and humans. In this study, we investigated the effects of 2-week mirabegron treatment on the metabolic parameters of mice with a diet-induced obesity (DIO). C57BL/6JUnib mice were divided into control (CTR) and obese (OB) groups treated with vehicle, and an OB group treated with mirabegron (OB + MIRA). The obese groups were fed a high-fat diet for 12 weeks. Mirabegron (10 mg/kg/day) was administrated orally by gavage from weeks 10-12.After 2 weeks of mirabegron treatment, the energy expenditure was assessed with indirect calorimetry. Blood glucose, insulin, glycerol, free fatty acids (FFA), thiobarbituric acid reactive substance (TBAR), and tumour necrosis factor (TNF)α levels were also assessed, and the HOMA index was determined. Liver tissue, brown adipose tissue (BAT), and inguinal white adipose tissue (iWAT) samples were collected for histological examination. The protein expressions of uncoupling protein 1 (UCP1) and mitochondrial transcription factor A (TFAM) were assessed using western blotting of the BAT and iWAT samples. In this study, mirabegron increased the energy expenditure and decreased adiposity in OB + MIRA. Increased UCP1 expression in BAT without changes in iWAT was also found. Mirabegron decreased circulating levels of FFA, glycerol, insulin, TNFα, TBARS and HOMA index. DIO significantly increased the lipid deposits in the liver and BAT, but mirabegron partially reversed this change. Our findings indicate that treatment with mirabegron decreased inflammation and improved metabolism in obese mice. This effect was associated with increased BAT-mediated energy expenditure, but not iWAT beiging, which suggests that mirabegron might be useful for the treatment of obesity and diabetes.

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“…Next, the synergistic effects of HTGT and EMIQ, a known thermogenic inducer were investigated [ 29 , 30 ]. The synergistic effects of co-treatment on brown adipocyte marker expression and mitochondrial content were determined by immunoblot analyses.…”

Section: Resultsmentioning

confidence: 99%

Anti-obesity effects of heat-transformed green tea extract through the activation of adipose tissue thermogenesis

Lee

Kim

et al. 2022

Nutr Metab (Lond)

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Background Adipose tissue thermogenesis is a potential therapeutic target to increase energy expenditure and thereby combat obesity. The aim of the present study was to investigate the thermogenic and anti-obesity effects of heat-transformed green tea extract (HTGT) and enzymatically modified isoquercetin (EMIQ). Methods Immortalized brown pre-adipocytes and C3H10T1/2 cells were used for in vitro analyses. A high-fat diet (HFD)-induced obesity mouse model and CIDEA-reporter mice were used for in vivo experiments. The effects of HTGT and EMIQ on mitochondrial metabolism were evaluated by immunoblot, mitochondrial staining, and oxygen consumption rate analyses. In vivo anti-obesity effects of HTGT and EMIQ were measured using indirect calorimetry, body composition analyses, glucose tolerance tests, and histochemical analyses. Results Co-treatment with HTGT and EMIQ (50 μg/mL each) for 48 h increased brown adipocyte marker and mitochondrial protein levels (UCP1 and COXIV) in brown adipocytes by 2.9-fold, while the maximal and basal oxygen consumption rates increased by 1.57- and 1.39-fold, respectively. Consistently, HTGT and EMIQ treatment increased the fluorescence intensity of mitochondrial staining in C3H10T1/2 adipocytes by 1.68-fold. The combination of HTGT and EMIQ (100 mg/kg each) increased the expression levels of brown adipocyte markers and mitochondrial proteins in adipose tissue. Two weeks of HTGT and EMIQ treatment (100 mg/kg each) led to a loss of 3% body weight and 7.09% of body fat. Furthermore, the treatment increased energy expenditure by 8.95% and improved glucose tolerance in HFD-fed mice. Conclusions The current study demonstrated that HTGT and EMIQ have in vivo anti-obesity effects partly by increasing mitochondrial metabolism in adipocytes. Our findings suggest that a combination of HTGT and EMIQ is a promising therapeutic agent for the treatment of obesity and related metabolic diseases.

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The effect of mirabegron on energy expenditure and brown adipose tissue in healthy lean South Asian and Europid men

Cited by 28 publications

References 59 publications

Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota

Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota

The effects of mirabegron on obesity‐induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue

Anti-obesity effects of heat-transformed green tea extract through the activation of adipose tissue thermogenesis

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