Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

Cell, Год журнала: 2021, Номер 184(13), С. 3502 - 3518.e33

Опубликована: Май 27, 2021

Язык: Английский

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β3-Adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity

Journal of Clinical Investigation, Год журнала: 2021, Номер 132(2)

Опубликована: Ноя. 30, 2021

The dysregulation of energy homeostasis in obesity involves multihormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine remains largely unexplored. Murine β3-adrenergic receptor expression adipocytes is orders magnitude higher compared with that other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) protein are dramatically downregulated after ligand exposure (homologous desensitization). β3-Adrenergic downregulation also occurs high-fat diet feeding, concurrent elevated inflammation. This recapitulated vitro by TNF-α treatment (heterologous Both homologous heterologous Adrb3 were triggered induction the pseudokinase TRIB1 downstream EPAC/RAP2A/PI-PLC pathway. turn degraded primary transcriptional activator Adrb3, CEBPα. EPAC/RAP inhibition enhanced catecholamine-stimulated lipolysis expenditure obese mice. Moreover, adipose tissue genes this pathway correlated body weight extremes a cohort genetically diverse mice BMI 2 independent cohorts humans. These data implicate signaling axis may explain reduced hormone-stimulated therapeutic interventions agonists.

Язык: Английский

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An update on brown adipose tissue biology: a discussion of recent findings

AJP Endocrinology and Metabolism, Год журнала: 2021, Номер 320(3), С. E488 - E495

Опубликована: Янв. 18, 2021

Brown adipose tissue (BAT) has been encouraged as a potential treatment for obesity and comorbidities due to its thermogenic activity capacity contribution energy expenditure. Some interventions such cold β-adrenergic drugs are able activate BAT thermogenesis well promote differentiation of white adipocytes into brown-like cells (browning), enhancing the these cells. In this mini-review, we discuss new mechanisms related regard, will also recent studies that have revealed existence important secretory molecules from "batokines" act in autocrine, paracrine, endocrine mechanisms, which turn may explain some beneficial roles on whole body glucose fat metabolism. Finally, insights with an additional focus distinct features metabolism between rodents humans.

Язык: Английский

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Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss

Obesity, Год журнала: 2022, Номер 30(4), С. 841 - 857

Опубликована: Март 25, 2022

Abstract New appetite‐regulating antiobesity treatments such as semaglutide and agents under investigation tirzepatide show promise in achieving weight loss of 15% or more. Energy expenditure, fat oxidation, lean mass preservation are important determinants weight‐loss maintenance beyond appetite regulation. This review discusses prior failures clinical development drugs targeting energy expenditure explores novel strategies for expenditure: mitochondrial proton leak, uncoupling, dynamics, biogenesis; futile calcium substrate cycling; leptin maintenance; increased sympathetic nervous system activity; browning white fat. Relevant targets preserving also reviewed: growth hormone, activin type II receptor inhibition, urocortin 2 3. We endorse moderate modulation combination with efficient reduction a means obtaining significant, safe, long‐lasting loss. Furthermore, we suggest that the regulatory guidelines should be revisited to focus more on quality its rather than absolute Commitment this research both from scientific point view could signal beginning next era obesity therapies.

Язык: Английский

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Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk

Frontiers in Endocrinology, Год журнала: 2021, Номер 12

Опубликована: Апрель 13, 2021

Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white (WAT) lipid-burning brown (BAT). After rediscovery presence metabolically active BAT adults, received increasing attention especially since activation is considered a promising way to combat obesity associated comorbidities. It become clear energy homeostasis differs between sexes, which significant impact on development pathological conditions such as type 2 diabetes. Sex differences activity may contribute this and, therefore, it important address underlying mechanisms sex activity. In review, we discuss role hormones regulation under physiological some conditions. Given number studies suggesting crosstalk hypothalamic-pituitary-adrenal axis metabolism, also relation

Язык: Английский

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Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues

Cells, Год журнала: 2021, Номер 10(11), С. 3030 - 3030

Опубликована: Ноя. 5, 2021

Obesity-associated metabolic abnormalities comprise a cluster of conditions including dyslipidemia, insulin resistance, diabetes and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from accumulation white adipose tissues mainly due to chronic imbalance energy intake expenditure. A variety approaches treat or prevent obesity, lifestyle interventions, surgical weight loss procedures pharmacological reduce increase expenditure have failed substantially decrease prevalence obesity. Brown tissue (BAT), primary source thermogenesis in infants small mammals may represent promising therapeutic target obesity by promoting through non-shivering mediated mitochondrial uncoupling protein 1 (UCP1). Since confirmation functional BAT adult humans several groups, approximately decade ago, its association with favorable phenotype, intense interest on significance human physiology health emerged within scientific community explore potential for treatment diseases. decreased activity individuals indicates role setting On other hand, mass correlate lower body index (BMI), age glucose levels, leading incidence cardio-metabolic The increased cold exposure undetectable was associated fat sensitivity. deeper understanding interrelationship distribution deciphering proper strategies expenditure, either increasing inducing browning, holds promise possible avenues disorders.

Язык: Английский

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Modelling metabolic diseases and drug response using stem cells and organoids

Nature Reviews Endocrinology, Год журнала: 2022, Номер 18(12), С. 744 - 759

Опубликована: Сен. 7, 2022

Язык: Английский

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Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat

Molecular Metabolism, Год журнала: 2022, Номер 61, С. 101499 - 101499

Опубликована: Апрель 22, 2022

Язык: Английский

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The Role of AMPK Signaling in Brown Adipose Tissue Activation

Cells, Год журнала: 2021, Номер 10(5), С. 1122 - 1122

Опубликована: Май 6, 2021

Obesity is becoming a pandemic, and its prevalence still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as possible target achieve this for functional role in energy expenditure by means increasing thermogenesis. An important metabolic sensor regulator whole-body balance AMP-activated protein kinase (AMPK), metabolism evident. This review highlights mechanisms BAT activation investigates how AMPK can be used activation. We compounds other factors able activate further discuss therapeutic use Extensive shows activated number different kinases, such LKB1, CaMKK, but also small molecules, hormones, stresses. inducing adipogenesis, maintaining mitochondrial homeostasis browning white tissue. conclude that, despite encouraging results, many uncertainties should clarified before posed anti-obesity treatment via

Язык: Английский

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The sympathetic nervous system in the 21st century: Neuroimmune interactions in metabolic homeostasis and obesity

Neuron, Год журнала: 2022, Номер 110(21), С. 3597 - 3626

Опубликована: Ноя. 1, 2022

Язык: Английский

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