Human brown adipose tissue — function and therapeutic potential in metabolic disease

Bhatt, Padmanabh; Dhillo, Waljit S.; Salem, Victoria

doi:10.1016/j.coph.2017.07.004

Cited by 25 publications

(12 citation statements)

References 89 publications

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“…Vast research is focusing on understanding regulatory factors involved in BAT metabolism, aiming to find new pharmacological approaches to activate thermogenesis and increase EE. This could serve as a potential new treatment strategy against the increasing epidemic of obesity and type 2 diabetes [5]. …”

Section: Introductionmentioning

confidence: 99%

Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT

Lahesmaa

Oikonen

Helin

et al. 2018

Eur J Nucl Med Mol Imaging

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Adenosine administration caused a maximal perfusion effect in human supraclavicular BAT, indicating increased oxidative metabolism. Cold exposure increased noradrenaline concentrations and decreased the density of A2AR available for radioligand binding in BAT, suggesting augmented release of endogenous adenosine. Our results show that adenosine and A2AR are relevant for activation of human BAT, and A2AR provides a future target for enhancing BAT metabolism.

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Section: Introductionmentioning

confidence: 99%

Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT

Lahesmaa

Oikonen

Helin

et al. 2018

Eur J Nucl Med Mol Imaging

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“…As a result, thermogenesis‐associated protein UCP1 was enhanced in iWAT by AKG intake. Cold exposure is a standard method to induce the browning of WAT and increase thermogenesis in BAT (Bhatt, Dhillo, & Salem, ; Dempersmier et al, ). Consistently, the UCP1 expression and thermogenic function of middle‐aged mice supplemented with AKG were further enhanced by cold exposure.…”

Section: Discussionmentioning

confidence: 99%

Dietary alpha‐ketoglutarate promotes beige adipogenesis and prevents obesity in middle‐aged mice

et al. 2019

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Aging usually involves the progressive development of certain illnesses, including diabetes and obesity. Due to incapacity to form new white adipocytes, adipose expansion in aged mice primarily depends on adipocyte hypertrophy, which induces metabolic dysfunction. On the other hand, brown adipose tissue burns fatty acids, preventing ectopic lipid accumulation and metabolic diseases. However, the capacity of brown/beige adipogenesis declines inevitably during the aging process.Previously, we reported that DNA demethylation in the Prdm16 promoter is required for beige adipogenesis. DNA methylation is mediated by ten-eleven family proteins (TET) using alpha-ketoglutarate (AKG) as a cofactor. Here, we demonstrated that the circulatory AKG concentration was reduced in middle-aged mice (10-month-old) compared with young mice (2-month-old). Through AKG administration replenishing the AKG pool, aged mice were associated with the lower body weight gain and fat mass, and improved glucose tolerance after challenged with high-fat diet (HFD).These metabolic changes are accompanied by increased expression of brown adipose genes and proteins in inguinal adipose tissue. Cold-induced brown/beige adipogenesis was impeded in HFD mice, whereas AKG rescued the impairment of beige adipocyte functionality in middle-aged mice. Besides, AKG administration up-regulated Prdm16 expression, which was correlated with an increase of DNA demethylation in the Prdm16 promoter. In summary, AKG supplementation promotes beige adipogenesis and alleviates HFD-induced obesity in middle-aged mice, which is associated with enhanced DNA demethylation of the Prdm16 gene. K E Y W O R D S adipose tissue browning, aging, alpha-ketoglutarate, DNA demethylation, glucose tolerance, high-fat diet S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Tian Q, Zhao J, Yang Q, et al. Dietary alpha-ketoglutarate promotes beige adipogenesis and prevents obesity in middle-aged mice. Aging Cell.

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“…Studies on brown adipose tissue (BAT) have been considered a promising opportunity to find a pharmaceutical intervention for the treatment of obesity with energy dissipation, and therefore, have attracted considerable attention. 10 – 12 BAT is a type of adipose tissue that had originally been observed in the interscapular region of rodents and newborn infants, and could uniquely induce non-shivering thermogenesis via un-coupling respiration licensed through un-coupling protein 1 (UCP1) on the mitochondrial membrane under cold exposure. 13 , 14 BAT is innervated by the sympathetic system and histological studies have shown that nerve fibers distribute both at the parenchymal space and around blood vessels of BAT.…”

Section: Introductionmentioning

confidence: 99%

<p>Long Non-Coding RNAs in Brown Adipose Tissue</p>

Lai

Shi

et al. 2020

DMSO

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Obesity has become a widespread disease that is harmful to human health. Fat homeostasis is essentially maintained by fat accumulation and energy expenditure. Studies on brown adipose tissue (BAT) represent a promising opportunity to identify a pharmaceutical intervention against obesity through increased energy expenditure. Long non-coding RNAs (lncRNAs) were thought to be critical regulators in a variety of biological processes. Recent studies have revealed that lncRNAs, including ones that are BAT-specific, conserved, and located at key protein-coding genes, function in brown adipogenesis, white adipose browning (ie, beige adipogenesis), and brown thermogenesis. In this review, we describe lncRNA properties and highlight functional lncRNAs in these biological processes, with the goal of establishing links between lncRNAs and BAT. Based on the advances of lncRNAs in the regulation of BAT, we discussed the advantages of potential lncRNA-based obesity drugs. Further BAT lncRNA-based drug development may provide new exciting approaches to defend obesity by regulation of fat homeostasis.

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Human brown adipose tissue — function and therapeutic potential in metabolic disease

Cited by 25 publications

References 89 publications

Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT

Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT

Dietary alpha‐ketoglutarate promotes beige adipogenesis and prevents obesity in middle‐aged mice

<p>Long Non-Coding RNAs in Brown Adipose Tissue</p>

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