Brown adipose tissue and lipid metabolism: New strategies for identification of activators and biomarkers with clinical potential

Xiang, Angie S.; Meikle, Peter J.; Carey, Andrew L.; Kingwell, Bronwyn A.

doi:10.1016/j.pharmthera.2018.07.002

Cited by 16 publications

(14 citation statements)

References 101 publications

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“…Brown/beige adipocytes secrete signalling factors, termed batokines that can act in endocrine, paracrine and/or autocrine fashion. A majority of so far identified batokines are small peptides (Villarroya et al, 2017), however, BAT also secretes non-peptide signalling molecules, such as microRNAs and lipids (Thomou et al, 2017;Xiang et al, 2018). Many of BAT-secreted factors act locally to control the remodelling of BAT and beige fat (Klepac et al, 2016), however, BAT also acts on peripheral or gans, such as the liver, skeletal muscle, pancreas, bone, the immune system and the CNS, affecting systemic glucose levels in a thermogenesis-dependent and -independent manner.…”

Section: Bat-mediated Endocrine Signals Involved In Glycaemic Controlmentioning

confidence: 99%

“…However, the main difficulty in establishing reliable biomarkers lies in the identification of molecules that are selective for BAT (Chen et al, 2016;Nakhuda et al, 2016). Perhaps a combination of several biomarkers could provide a more accurate estimation of BAT activity; the increasing use of screening methods for BAT-secreted factors and metabolites will most certainly help to achieve this goal (Xiang et al, 2018).…”

Section: Studymentioning

confidence: 99%

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The role of brown and beige adipose tissue in glycaemic control

Klepac

Georgiadi

Tschöp

et al. 2019

Molecular Aspects of Medicine

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For the past decade, brown adipose tissue (BAT) has been extensively studied as a potential therapy for obesity and metabolic diseases due to its thermogenic and glucose-consuming properties. It is now clear that the function of BAT goes beyond heat production, as it also plays an important endocrine role by secreting the so-called batokines to communicate with other metabolic tissues and regulate systemic energy homeostasis. However, despite numerous studies showing the benefits of BAT in rodents, it is still not clear whether recruitment of BAT can be utilized to treat human patients. Here, we review the advances on understanding the role of BAT in metabolism and its benefits on glucose and lipid homeostasis in both humans and rodents. Moreover, we discuss the latest methodological approaches to assess the contribution of BAT to human metabolism as well as the possibility to target BAT, pharmacologically or by lifestyle adaptations, to treat metabolic disorders.

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Section: Bat-mediated Endocrine Signals Involved In Glycaemic Controlmentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

The role of brown and beige adipose tissue in glycaemic control

Klepac

Georgiadi

Tschöp

et al. 2019

Molecular Aspects of Medicine

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“…This is due to BAT’s capacity for non-shivering thermogenesis, which contributes to increased whole-body energy expenditure. Recent studies have suggested that adult humans possess >1 kg of adipose tissue capable of thermogenesis (“brownable” adipose tissue) [ 1 ], the maximal activation of which could increase whole body energy expenditure by ~25% [ 7 ]. However, to date it has not been possible to increase BAT energy expenditure by this magnitude in humans through chronic administration of pharmacological agents [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…NEFAs are a heterogenous class of lipids differing in chain length, degree of saturation and location of double bonds. There is ongoing speculation whether distinct NEFA species are integral in regulation of BAT activation and thermogenesis [ 7 , 11 , 16 ]. While the species-specific effects of NEFAs on BAT have not been described in human clinical studies, induction of Ucp1 expression has been observed in cultured human pre-adipocytes stimulated with the omega-3 polyunsaturated NEFA eicosapentaenoic acid (EPA; C20:5 n3), while docosahexaenoic acid (DHA; C22:6 n3) and arachidonic acid (AA; C20:4 n6) were without effect [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans

et al. 2020

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Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species—in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.

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“…In human adults, beige adipocytes are present in supraclavicular fat of human body (15,16). The activation of brown adipocytes has been considered an attractive target for therapeutic intervention in obesity and metabolic diseases (17)(18)(19)(20)(21). Studies in mouse models have shown that BAT activation can improve hyperlipidemia and harmful effects of obesity (5,22).…”

Section: Introductionmentioning

confidence: 99%

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

Jia

Fang

et al. 2020

Preprint

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Beige adipocytes are emerging as an interesting issue in obesity and metabolism research. There is a neglected possibility that brown adipocytes are equally activated when external stimuli induce beige adipocytes. Thus, a question is whether beige adipocytes have the same functions as brown adipocytes when brown adipose tissue (BAT) is lacking. This question has not been well studied. Therefore we determine the beneficial effects of beige adipocytes upon cold challenge or CL316243 treatments in animal models of BAT ablation by surgical denervation. The data show that beige adipocytes partly contribute to impaired glucose metabolism resulting from denervated BAT. Whereas, we found that denervated BAT were activated by cold exposure and CL316243. Thus, we further used BAT-removal animal models to abolish BAT functions completely. We found that beige adipocytes upon cold challenge or CL316243 treatments independently improved impaired glucose metabolism in BAT-removal mice. The insulin signaling was activated in BAT-removal mice upon cold exposure. Whereas, both the activation of insulin signaling and up-regulation of glucose transporter expression were observed in BAT-removal mice with CL316243 treatments. The data show that beige adipocytes induced by cold exposure or CL316243 may have different mechanisms to improve impaired glucose metabolism. Beige adipocytes can also enhance energy expenditure and lipolytic activity of white adipose tissue when BAT is lacking. We provide direct evidences for the beneficial effect of beige adipocytes in glucose metabolism and energy expenditure in the absence of BAT in vivo.

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Brown adipose tissue and lipid metabolism: New strategies for identification of activators and biomarkers with clinical potential

Cited by 16 publications

References 101 publications

The role of brown and beige adipose tissue in glycaemic control

The role of brown and beige adipose tissue in glycaemic control

Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

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