Substrate Utilization by Brown Adipose Tissue: What’s Hot and What’s Not?

McNeill, Ben T; Morton, Nicholas M.; Stimson, Roland H

doi:10.3389/fendo.2020.571659

Cited by 48 publications

(34 citation statements)

References 71 publications

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“…Mitochondrial functions and capacity can also be enhanced by brown adipose tissue, which is metabolically activated by cold exposure [ 43 , 44 ]. Recently, Kovaničová et al [ 45 ] have reported that cold-acclimatized ice-water swimmers respond to cold by non-shivering thermogenesis mediated by higher fat oxidation than controls.…”

Section: Discussionmentioning

confidence: 99%

A Possible Preventive Role of Physically Active Lifestyle during the SARS-CoV-2 Pandemic; Might Regular Cold-Water Swimming and Exercise Reduce the Symptom Severity of COVID-19?

Bielik

Grendár

Kolísek

2021

IJERPH

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The objective of this study was to investigate the incidence and course of COVID-19 and the risk of an upper respiratory tract infection in a group of people with physically active lifestyles. Data were collected anonymously using an online survey platform during December 2020. The age of participants ranged from 18 to 65 years. Out of 2343 participants, 11.5% overcame COVID-19 infection. Relative to the control group (CTRL), physically active, cold-water swimmers (PACW) did not exhibit a lower risk of incidence for COVID-19 (RR 1.074, CI 95% (0.710–1.625). However, PACW had a higher chance of having an asymptomatic course of COVID-19 (RR 2.321, CI 95% (0.836–6.442); p < 0.05) and a higher chance of only having an acute respiratory infection once or less per year than CTRL (RR 1.923, CI 95% (1.1641–2.253); p < 0.01). Furthermore, PACW exhibited a lower incidence of acute respiratory infection occurring more than twice per year (RR 0.258, CI 95% (0.138–0.483); p < 0.01). Cold-water swimming and physical activity may not lessen the risk of COVID-19 in recreational athletes. However, a physically active lifestyle might have a positive effect on the rate of incidence of acute respiratory infection and on the severity of COVID-19 symptoms.

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Section: Discussionmentioning

confidence: 99%

A Possible Preventive Role of Physically Active Lifestyle during the SARS-CoV-2 Pandemic; Might Regular Cold-Water Swimming and Exercise Reduce the Symptom Severity of COVID-19?

Bielik

Grendár

Kolísek

2021

IJERPH

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“…Though LDB1 may regulate Ucp1 to affect cold tolerance, reductions in additional gene targets involved in lipid metabolism and thyroid signaling (e.g., Elovl3 , Dio2 ) likely contribute to the severe cold intolerance phenotype. Substrates like glucose and fatty acids are either oxidized as fuel for thermogenesis or used to replenish intercellular lipid pools [ 34 , 35 ]. Given the importance of metabolites for adipocyte thermogenesis, models affecting substrate uptake and utilization, including an adipose triglyceride lipase (ATGL) knockout model, also result in cold intolerance phenotypes [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

The transcriptional co-regulator LDB1 is required for brown adipose function

Kepple

Liu

Kim

et al. 2021

Molecular Metabolism

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Objective Brown adipose tissue (BAT) is critical for thermogenesis and glucose/lipid homeostasis. Exploiting the energy uncoupling capacity of BAT may reveal targets for obesity therapies. This exploitation requires a greater understanding of the transcriptional mechanisms underlying BAT function. One potential regulator of BAT is the transcriptional co-regulator LIM domain-binding protein 1 (LDB1), which acts as a dimerized scaffold, allowing for the assembly of transcriptional complexes. Utilizing a global LDB1 heterozygous mouse model, we recently reported that LDB1 might have novel roles in regulating BAT function. However, direct evidence for the LDB1 regulation of BAT thermogenesis and substrate utilization has not been elucidated. We hypothesize that brown adipocyte-expressed LDB1 is required for BAT function. Methods LDB1-deficient primary cells and brown adipocyte cell lines were assessed via qRT-PCR and western blotting for altered mRNA and protein levels to define the brown adipose-specific roles. We conducted chromatin immunoprecipitation with primary BAT tissue and immortalized cell lines. Potential transcriptional partners of LDB1 were revealed by conducting LIM factor surveys via qRT-PCR in mouse and human brown adipocytes. We developed a Ucp1 -Cre-driven LDB1-deficiency mouse model, termed Ldb1 ΔBAT , to test LDB1 function in vivo . Glucose tolerance and uptake were assessed at thermoneutrality via intraperitoneal glucose challenge and glucose tracer studies. Insulin tolerance was measured at thermoneutrality and after stimulation with cold or the administration of the β3-adrenergic receptor (β3-AR) agonist CL316,243. Additionally, we analyzed plasma insulin via ELISA and insulin signaling via western blotting. Lipid metabolism was evaluated via BAT weight, histology, lipid droplet morphometry, and the examination of lipid-associated mRNA. Finally, energy expenditure and cold tolerance were evaluated via indirect calorimetry and cold challenges. Results Reducing Ldb1 in vitro and in vivo resulted in altered BAT-selective mRNA, including Ucp1 , Elovl3 , and Dio2 . In addition, there was reduced Ucp1 induction in vitro . Impacts on gene expression may be due, in part, to LDB1 occupying Ucp1 upstream regulatory domains. We also identified BAT-expressed LIM-domain factors Lmo2 , Lmo4 , and Lhx8 , which may partner with LDB1 to mediate activity in brown adipocytes. Additionally, we observed LDB1 enrichment in human brown adipose. In vivo analysis revealed LDB1 i...

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“…2 ). In addition to triglyceride stores, BAT sequesters and utilises several circulating substrates such as glucose, fatty acids and some amino acids during thermogenesis (reviewed in ( 23 )). Therefore, BAT activation may improve other metabolic health parameters such as hyperglycaemia and dyslipidaemia in addition to increasing energy expenditure.…”

Section: The Distribution and Function Of Brown And Beige Adipose Tissuementioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Human brown adipose tissue as a therapeutic target: warming up or cooling down?

McNeill

Suchacki

Stimson

2021

European Journal of Endocrinology

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Excessive accumulation of white adipose tissue leads to obesity and its associated metabolic health consequences such as type 2 diabetes and cardiovascular disease. Several approaches to treat or prevent obesity including public health interventions, surgical weight loss, and pharmacological approaches to reduce caloric intake have failed to substantially modify the increasing prevalence of obesity. The (re-)discovery of active brown adipose tissue (BAT) in adult humans approximately 15 years ago led to a resurgence in research into whether BAT activation could be a novel therapy for the treatment of obesity. Upon cold stimulus, BAT is activated and generates heat to maintain body temperature, thus increasing energy expenditure. Activation of BAT may provide a unique opportunity to increase energy expenditure without the need for exercise. However, much of the underlying mechanisms surrounding BAT activation are still being elucidated and the effectiveness of BAT as a therapeutic target has not been realised. Research is ongoing to determine how best to expand BAT mass and activate existing BAT; approaches include cold exposure, pharmacological stimulation using sympathomimetics, browning agents that induce formation of thermogenic beige adipocytes in white adipose depots, and the identification of factors secreted by BAT with therapeutic potential. In this review, we discuss the caloric capacity and other metabolic benefits from BAT activation in humans and the role of metabolic tissues such as skeletal muscle in increasing energy expenditure. We discuss the potential of current approaches and the challenges of BAT activation as a novel strategy to treat obesity and metabolic disorders.

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Substrate Utilization by Brown Adipose Tissue: What’s Hot and What’s Not?

Cited by 48 publications

References 71 publications

A Possible Preventive Role of Physically Active Lifestyle during the SARS-CoV-2 Pandemic; Might Regular Cold-Water Swimming and Exercise Reduce the Symptom Severity of COVID-19?

A Possible Preventive Role of Physically Active Lifestyle during the SARS-CoV-2 Pandemic; Might Regular Cold-Water Swimming and Exercise Reduce the Symptom Severity of COVID-19?

The transcriptional co-regulator LDB1 is required for brown adipose function

MECHANISMS IN ENDOCRINOLOGY: Human brown adipose tissue as a therapeutic target: warming up or cooling down?

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