mirabegron has been researched along with Obesity* in 9 studies
2 review(s) available for mirabegron and Obesity
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The colorful versatility of adipocytes: white-to-brown transdifferentiation and its therapeutic potential in humans.
Brown and brite adipocytes contribute to energy expenditure through nonshivering thermogenesis. Though these cell types are thought to arise primarily from the de novo differentiation of precursor cells, their abundance is also controlled through the transdifferentiation of mature white adipocytes. Here, we review recent advances in our understanding of the regulation of white-to-brown transdifferentiation, as well as the conversion of brown and brite adipocytes to dormant, white-like fat cells. Converting mature white adipocytes into brite cells or reactivating dormant brown and brite adipocytes has emerged as a strategy to ameliorate human metabolic disorders. We analyze the evidence of learning from mice and how they translate to humans to ultimately scrutinize the relevance of this concept. Moreover, we estimate that converting a small percentage of existing white fat mass in obese subjects into active brite adipocytes could be sufficient to achieve meaningful benefits in metabolism. In conclusion, novel browning agents have to be identified before adipocyte transdifferentiation can be realized as a safe and efficacious therapy. Topics: Acetanilides; Adipocytes, Beige; Adipocytes, Brown; Adipocytes, White; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Cell Lineage; Cell Transdifferentiation; Diabetes Mellitus; Drugs, Investigational; Energy Metabolism; Humans; Imatinib Mesylate; Obesity; Roscovitine; Thermogenesis; Thiazoles | 2021 |
Mirabegron: The most promising adipose tissue beiging agent.
Accumulation of white adipose tissue (WAT) underlies the obesity epidemic, leading to current therapeutic techniques that are being investigated for their ability to activate/"beige" this tissue. Adipose tissue (AT) beiging has been reported through intermittent cold exposure (CE), exercise, and β3-Adrenergic Receptor (β3AR) agonists. But how AT beiging can help in the treatment of metabolic disorders like obesity and type 2 diabetes (T2D) remains largely unexplored. This review summarizes recent research on the use of β3AR agonist, mirabegron (Myrbetriq®), in stimulating beiging in AT. Researchers have only recently been able to determine the optimal therapeutic dose of mirabegron for inducing beiging in subcutaneous/ inguinal WAT, where the benefits of AT activation are evident without the undesired cardiovascular side effects. To determine whether the effects that mirabegron elicits are metabolically beneficial, a comparison of the undisputed findings resulting from intermittent CE-induced beiging and the disputed findings from exercise-induced beiging was conducted. Given the recent in vivo animal and clinical studies, the understanding of how mirabegron can be metabolically beneficial for both lean and obese individuals is more clearly understood. These studies have demonstrated that circulating adipokines, glucose metabolism, and lipid droplet (LD) size are all positively affected by mirabegron administration. Recent studies have also demonstrated that mirabegron has similar outcomes to intermittent CE and displays more direct evidence for beiging than those produced with exercise. With these current findings, mirabegron is considered the most promising and safest β3AR agonist currently available that has the potential to be used in the therapeutic treatment of metabolic disorders, and future studies into its interaction with different conditions may prove to be useful as part of a treatment plan in combination with a healthy diet and exercise. Topics: Acetanilides; Adipose Tissue; Adipose Tissue, White; Animals; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Obesity; Thiazoles | 2021 |
3 trial(s) available for mirabegron and Obesity
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The β3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans.
BACKGROUNDBeige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.METHODSBefore and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and activity, and we conducted in vitro studies with primary cultures of differentiated human adipocytes and muscle.RESULTSThe clinical effects of mirabegron treatment included improved oral glucose tolerance (P < 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and β cell function (P = 0.01). In SC WAT, mirabegron treatment stimulated lipolysis, reduced fibrotic gene expression, and increased alternatively activated macrophages. Subjects with the most SC WAT beiging showed the greatest improvement in β cell function. In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPARγ coactivator 1 α (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001).CONCLUSIONMirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since β cells and skeletal muscle do not express β3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves β cell function.TRIAL REGISTRATIONClinicaltrials.gov NCT02919176.FUNDINGNIH: DK112282, P30GM127211, DK 71349, and Clinical and Translational science Awards (CTSA) grant UL1TR001998. Topics: Acetanilides; Adipocytes; Adipose Tissue, Beige; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Biopsy; Blood Glucose; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Muscle, Skeletal; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Thiazoles | 2020 |
Human adipose beiging in response to cold and mirabegron.
The induction of beige adipocytes in s.c. white adipose tissue (WAT) depots of humans is postulated to improve glucose and lipid metabolism in obesity. The ability of obese, insulin-resistant humans to induce beige adipose tissue is unknown.. We exposed lean and obese research participants to cold (30-minute ice pack application each day for 10 days of the upper thigh) or treated them with the β3 agonist mirabegron. We determined beige adipose marker expression by IHC and quantitative PCR, and we analyzed mitochondrial bioenergetics and UCP activity with an Oxytherm system.. Cold significantly induced UCP1 and TMEM26 protein in both lean and obese subjects, and this response was not associated with age. Interestingly, these proteins increased to the same extent in s.c. WAT of the noniced contralateral leg, indicating a crossover effect. We further analyzed the bioenergetics of purified mitochondria from the abdominal s.c. WAT of cold-treated subjects and determined that repeat ice application significantly increased uncoupled respiration, consistent with the UCP1 protein induction and subsequent activation. Cold also increased State 3 and maximal respiration, and this effect on mitochondrial bioenergetics was stronger in summer than winter. Chronic treatment (10 weeks; 50 mg/day) with the β3 receptor agonist mirabegron induces UCP1, TMEM26, CIDEA, and phosphorylation of HSL on serine660 in obese subjects.. Cold or β3 agonists cause the induction of beige adipose tissue in human s.c. WAT; this phenomenon may be exploited to increase beige adipose in older, insulin-resistant, obese individuals.. Clinicaltrials.gov NCT02596776, NCT02919176.. NIH (DK107646, DK112282, P20GM103527, and by CTSA grant UL1TR001998). Topics: Acetanilides; Adipose Tissue, Beige; Adrenergic beta-3 Receptor Agonists; Adult; Biopsy; Cold Temperature; Energy Metabolism; Female; Humans; Lipid Metabolism; Male; Membrane Proteins; Middle Aged; Obesity; Subcutaneous Fat; Thermogenesis; Thiazoles; Uncoupling Protein 1 | 2018 |
Activation of human brown adipose tissue by a β3-adrenergic receptor agonist.
Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of β3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a β3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via (18)F-fluorodeoxyglucose ((18)F-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 ± 40 kcal/day (+13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a β3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease. Topics: Acetanilides; Adipose Tissue, Brown; Adrenergic Agonists; Basal Metabolism; Chromatography, High Pressure Liquid; Fluorodeoxyglucose F18; Glucose; Humans; Male; Obesity; Positron-Emission Tomography; Receptors, Adrenergic, beta-3; Tandem Mass Spectrometry; Thiazoles; Tomography, X-Ray Computed; Young Adult | 2015 |
4 other study(ies) available for mirabegron and Obesity
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Pioglitazone does not synergize with mirabegron to increase beige fat or further improve glucose metabolism.
BACKGROUNDBeige and brown adipose tissue (BAT) are associated with improved metabolic homeostasis. We recently reported that the β3-adrenergic receptor agonist mirabegron induced beige adipose tissue in obese insulin-resistant subjects, and this was accompanied by improved glucose metabolism. Here we evaluated pioglitazone treatment with a combination pioglitazone and mirabegron treatment and compared these with previously published data evaluating mirabegron treatment alone. Both drugs were used at FDA-approved dosages.METHODSWe measured BAT by PET CT scans, measured beige adipose tissue by immunohistochemistry, and comprehensively characterized glucose and lipid homeostasis and insulin sensitivity by euglycemic clamp and oral glucose tolerance tests. Subcutaneous white adipose tissue, muscle fiber type composition and capillary density, lipotoxicity, and systemic inflammation were evaluated by immunohistochemistry, gene expression profiling, mass spectroscopy, and ELISAs.RESULTSTreatment with pioglitazone or the combination of pioglitazone and mirabegron increased beige adipose tissue protein marker expression and improved insulin sensitivity and glucose homeostasis, but neither treatment induced BAT in these obese subjects. When the magnitude of the responses to the treatments was evaluated, mirabegron was found to be the most effective at inducing beige adipose tissue. Although monotherapy with either mirabegron or pioglitazone induced adipose beiging, combination treatment resulted in less beiging than either alone. The 3 treatments also had different effects on muscle fiber type switching and capillary density.CONCLUSIONThe addition of pioglitazone to mirabegron treatment does not enhance beiging or increase BAT in obese insulin-resistant research participants.TRIAL REGISTRATIONClinicalTrials.gov NCT02919176.FUNDINGNIH DK112282 and P20GM103527 and Clinical and Translational Science Awards grant UL1TR001998. Topics: Acetanilides; Adipose Tissue, Beige; Drug Synergism; Female; Glucose; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Middle Aged; Obesity; Pioglitazone; Thiazoles | 2021 |
Beneficial Metabolic Effects of Mirabegron In Vitro and in High-Fat Diet-Induced Obese Mice.
Topics: 3T3-L1 Cells; Acetanilides; Adipocytes; Adipocytes, Brown; Animals; Body Weight; Diet, High-Fat; Gene Expression Regulation; Glucose; Homeostasis; Male; Mice; Mice, Obese; Obesity; Thiazoles; Uncoupling Protein 1 | 2019 |
Long-term treatment with the beta-3 adrenoceptor agonist, mirabegron ameliorates detrusor overactivity and restores cyclic adenosine monophosphate (cAMP) levels in obese mice.
To evaluate the effects of the beta-3 adrenoceptor agonist, mirabegron in a mouse model of detrusor overactivity induced by obesity.. C57BL/6 male mice were fed with standard chow or high-fat diet for 12 weeks. Lean and obese mice were treated orally with mirabegron (10 mg/kg/day) from the last 2 weeks of diet. Cystometric evaluations, functional assays, protein expression for phosphodiesterase type 4 (PDE4), and cyclic adenosine monophosphate (cAMP) measurement were carried out.. In obese mice the body weight, epididymal fat mass, fasting glucose, and low-density lipoprotein (LDL) levels were higher (P < 0.001) than in the lean mice. A reduction of 34% and 54% and an increase of 35% in the epididimal fat, LDL, and HDL levels (P < 0.05), respectively, were observed in the obese group treated with mirabegron, whereas no changes were seen in the lipid profile from lean mice. Obese group showed irregular micturition pattern, characterized by significant increases in frequency and non-void contractions. Carbachol, potassium chloride, and electrical-field stimulation induced detrusor smooth muscle (DSM) contractions, which were greater in bladders from obese mice than from lean mice. Two-week treatment with mirabegron restored all the contractile response alterations in the DSM. Basal intracellular levels of cAMP were reduced (68%), whereas PDE4 protein expression was increased (54%) in bladder from obese mice. Mirabegron restored the cAMP levels in obese bladder, without changing the PDE4 expression.. Mirabegron was able to completely restore the urinary alterations seen in the bladder from obese mice. Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Body Weight; Carbachol; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 4; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle Contraction; Muscle, Smooth; Obesity; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urination | 2017 |
Urogynecology digest : presented by Fiona M. Lindo.
Topics: Acetanilides; Bariatric Surgery; Cystitis, Interstitial; Female; Gynecology; Humans; Muscarinic Antagonists; Obesity; Pelvic Floor Disorders; Thiazoles; Urinary Bladder, Overactive; Urology | 2014 |