Brown adipose tissue is associated with cardiometabolic health

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(1), P. 58 - 65

Published: Jan. 1, 2021

Language: Английский

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The cellular and functional complexity of thermogenic fat

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(6), P. 393 - 409

Published: March 23, 2021

Language: Английский

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Reassessing Human Adipose Tissue

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 386(8), P. 768 - 779

Published: Feb. 23, 2022

Adipose tissue can more than double in mass and then return to baseline. This review discusses the functional roles of human white brown adipose its excess obesity, as well far-reaching, complementary physiological endocrine system.

Language: Английский

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Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(2), P. 287 - 300.e7

Published: Aug. 1, 2020

Language: Английский

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Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(17), P. 6241 - 6241

Published: Aug. 28, 2020

The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies restore the energy balance. Therefore, concept of activating brown adipose tissue (BAT) in order increase expenditure has been revived. In mammals, two developmentally distinct types adipocytes exist; classical or constitutive BAT that arises during embryogenesis, and beige is recruited postnatally within white (WAT) process called browning. Research recent years significantly increased our understanding mechanisms involved activation WAT They also allowed for identification critical molecules steps both processes and, therefore, many targets. Several non-pharmacological approaches, as well chemical compounds aiming at induction browning activation, have tested vitro animal models genetically determined and/or diet-induced obesity. potential some these humans. this review, we summarize present concepts regarding targets available them.

Language: Английский

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GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(12)

Published: May 18, 2021

Tirzepatide (LY3298176), a dual GIP and GLP-1 receptor (GLP-1R) agonist, delivered superior glycemic control weight loss compared with GLP-1R agonism in patients type 2 diabetes. However, the mechanism by which tirzepatide improves efficacy how (GIPR) contributes is not fully understood. Here, we show that an effective insulin sensitizer, improving sensitivity obese mice to greater extent than agonism. To determine whether GIPR contributes, effect of WT Glp-1r–null mice. In absence GLP-1R–induced loss, improved enhancing glucose disposal white adipose tissue (WAT). support this, long-acting agonist (LAGIPRA) was found enhance augmenting WAT. Interestingly, LAGIPRA on associated reduced branched-chain amino acids (BCAAs) ketoacids circulation. Insulin sensitization upregulation genes catabolism glucose, lipid, BCAAs brown tissue. Together, our studies weight-dependent -independent manner. These results highlight therapeutic profile dual-receptor agonism, offering mechanistic insights into clinical tirzepatide.

Language: Английский

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β3-Adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis

JCI Insight, Journal Year: 2021, Volume and Issue: 6(11)

Published: June 8, 2021

β3-Adrenergic receptors (β3-ARs) are the predominant regulators of rodent brown adipose tissue (BAT) thermogenesis. However, in humans, physiological relevance BAT and β3-AR remains controversial. Herein, using primary human adipocytes from supraclavicular neck fat immortalized brown/beige deep 2 subjects, we demonstrate that plays a critical role regulating lipolysis, glycolysis, Silencing compromised genes essential for thermogenesis, fatty acid metabolism, mitochondrial mass. Functionally, reduction lowered agonist-mediated increases intracellular cAMP, lipolysis-activated, uncoupling protein 1–mediated thermogenic capacity. Furthermore, mirabegron, selective agonist, stimulated lipolysis both processes were lost after silencing expression. This study highlights β3-ARs required to maintain multiple components lipolytic cellular machinery agonists could be used achieve metabolic benefit humans.

Language: Английский

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The evolving view of thermogenic adipocytes — ontogeny, niche and function

Nature Reviews Endocrinology, Journal Year: 2021, Volume and Issue: 17(12), P. 726 - 744

Published: Oct. 8, 2021

Language: Английский

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Defining the lineage of thermogenic perivascular adipose tissue

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(4), P. 469 - 484

Published: April 12, 2021

Language: Английский

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Brown Adipose Tissue—A Translational Perspective

Endocrine Reviews, Journal Year: 2022, Volume and Issue: 44(2), P. 143 - 192

Published: May 29, 2022

Abstract Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by central nervous and endocrine systems circulating metabolites, plausible roles of this in human thermoregulation, energy balance, disorders, current knowledge on pharmacological stimulation humans. The definition measurement studies relies almost exclusively glucose uptake from positron emission tomography with 18F-fluorodeoxiglucose, which can be dissociated thermogenic activity, as example insulin-resistant states. most important substrate thermogenesis is intracellular fatty acid content mobilized sympathetic triglyceride lipolysis. This lipolytic response intertwined white (WAT) other metabolic tissues, cannot independently stimulated drugs tested thus far. an interesting biologically has yet fully selectively activated increase body’s shift balance. field research need methods able directly, specifically, reliably measure while also tracking related responses WAT tissues. Until achieved, uncertainty will remain about role played fascinating

Language: Английский

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