Nature Metabolism, Год журнала: 2023, Номер 5(9), С. 1461 - 1474
Опубликована: Сен. 14, 2023
Язык: Английский
Nature Metabolism, Год журнала: 2023, Номер 5(9), С. 1461 - 1474
Опубликована: Сен. 14, 2023
Язык: Английский
Cell, Год журнала: 2021, Номер 184(13), С. 3502 - 3518.e33
Опубликована: Май 27, 2021
Язык: Английский
Процитировано
102Journal 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
Процитировано
85AJP 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
Процитировано
79Obesity, 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
Процитировано
71Frontiers 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
Процитировано
65Cells, 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
Процитировано
60Nature Reviews Endocrinology, Год журнала: 2022, Номер 18(12), С. 744 - 759
Опубликована: Сен. 7, 2022
Язык: Английский
Процитировано
60Molecular Metabolism, Год журнала: 2022, Номер 61, С. 101499 - 101499
Опубликована: Апрель 22, 2022
Язык: Английский
Процитировано
58Cells, 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
Процитировано
57Neuron, Год журнала: 2022, Номер 110(21), С. 3597 - 3626
Опубликована: Ноя. 1, 2022
Язык: Английский
Процитировано
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