Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis

This study describes the identification of Mfsd2a (major facilitator superfamily domain-containing protein 2a), a novel mammalian major facilitator superfamily domain-containing protein, and an additional closely related protein, Mfsd2b. Most intron/exon junctions are conserved between the two genes, suggesting that they are derived from a common ancestor. Mfsd2a and Mfsd2b share a 12 transmembrane α-helical domain structure that bears greatest similarity to that of the bacterial Na+/melibiose symporters. Confocal microscopy demonstrated that Mfsd2a localizes to the endoplasmic reticulum. Mfsd2a is expressed in many tissues and is highly induced in liver and BAT (brown adipose tissue) during fasting. Mfsd2a displays an oscillatory expression profile in BAT and liver, consistent with a circadian rhythm. Although the basal level of Mfsd2a expression is relatively low in mouse BAT, it is greatly induced during cold-induced thermogenesis and after treatment with βAR (β-adrenergic receptor) agonists. This induction is totally abolished in β-less (βAR-deficient) mice. These findings indicate that Mfsd2a is greatly up-regulated in BAT during thermogenesis and that its induction is controlled by the βAR signalling pathway. The observed induction of Mfsd2a expression in cultured BAT cells by dibutyryl-cAMP is in agreement with this conclusion. The present study suggests that Mfsd2a plays a role in adaptive thermogenesis.

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Brown adipose tissue is the key depot for glucose clearance in microbiota depleted mice

Nature Communications ◽

10.1038/s41467-021-24659-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Min Li ◽

Li Li ◽

Baoguo Li ◽

Catherine Hambly ◽

Guanlin Wang ◽

...

Keyword(s):

Adipose Tissue ◽

Gut Microbiota ◽

Brown Adipose Tissue ◽

Glucose Uptake ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Adaptive Thermogenesis ◽

Brown Adipose ◽

Glucose Clearance ◽

Deficient Mice

AbstractGut microbiota deficient mice demonstrate accelerated glucose clearance. However, which tissues are responsible for the upregulated glucose uptake remains unresolved, with different studies suggesting that browning of white adipose tissue, or modulated hepatic gluconeogenesis, may be related to enhanced glucose clearance when the gut microbiota is absent. Here, we investigate glucose uptake in 22 different tissues in 3 different mouse models. We find that gut microbiota depletion via treatment with antibiotic cocktails (ABX) promotes glucose uptake in brown adipose tissue (BAT) and cecum. Nevertheless, the adaptive thermogenesis and the expression of uncoupling protein 1 (UCP1) are dispensable for the increased glucose uptake and clearance. Deletion of Ucp1 expressing cells blunts the improvement of glucose clearance in ABX-treated mice. Our results indicate that BAT and cecum, but not white adipose tissue (WAT) or liver, contribute to the glucose uptake in the gut microbiota depleted mouse model and this response is dissociated from adaptive thermogenesis.

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Faculty Opinions recommendation of Activation of human brown adipose tissue by a β3-adrenergic receptor agonist.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725298188.793502828 ◽

2015 ◽

Author(s):

Michael Symonds

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Adrenergic Receptor ◽

Receptor Agonist ◽

Brown Adipose ◽

Adrenergic Receptor Agonist

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Changes in β1- and β2-adrenergic receptor mRNA levels in brown adipose tissue and heart of hypothyroid rats

Biochemical Journal ◽

10.1042/bj2770625 ◽

1991 ◽

Vol 277 (3) ◽

pp. 625-629 ◽

Cited By ~ 30

Author(s):

J P Revelli ◽

R Pescini ◽

P Muzzin ◽

J Seydoux ◽

M G Fitzgerald ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Adrenergic Receptor ◽

State Level ◽

Total Density ◽

Mrna Levels ◽

Interscapular Brown Adipose Tissue ◽

Brown Adipose ◽

Displacement Experiments ◽

Beta 2

The aim of the present work was to study the effect of hypothyroidism on the expression of the beta-adrenergic receptor (beta-AR) in interscapular brown adipose tissue and heart. The total density of plasma membrane beta-AR per tissue is decreased by 44% in hypothyroid rat interscapular brown adipose tissue and by 55% in hypothyroid rat heart compared with euthyroid controls. The effects of hypothyroidism on the density of both beta 1- and beta 2-AR subtypes were also determined in competition displacement experiments. The densities of beta 1- and beta 2-AR per tissue are decreased by 50% and 48% respectively in interscapular brown adipose tissue and by 52% and 54% in the heart. Northern blot analysis of poly(A)+ RNA from hypothyroid rat interscapular brown adipose tissue demonstrated that the levels of beta 1- and beta 2-AR mRNA per tissue are decreased by 73% and 58% respectively, whereas in hypothyroid heart, only the beta 1-AR mRNA is decreased, by 43%. The effect of hypothyroidism on the beta 1-AR mRNA is significantly more marked in the interscapular brown adipose tissue than in the heart. These results indicate that beta-AR mRNA levels are differentially regulated in rat interscapular brown adipose tissue and heart, and suggest that the decrease in beta-AR number in interscapular brown adipose tissue and heart of hypothyroid animals may in part be explained by a decreased steady-state level of beta-AR mRNA.

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Mice with Targeted Disruption of the Dio2 Gene Have Cold-Induced Overexpression of the Uncoupling Protein 1 Gene but Fail to Increase Brown Adipose Tissue Lipogenesis and Adaptive Thermogenesis

Diabetes ◽

10.2337/diabetes.53.3.577 ◽

2004 ◽

Vol 53 (3) ◽

pp. 577-584 ◽

Cited By ~ 140

Author(s):

M. A. Christoffolete ◽

C. C.G. Linardi ◽

L. de Jesus ◽

K. N. Ebina ◽

S. D. Carvalho ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Uncoupling Protein 1 ◽

Targeted Disruption ◽

Adaptive Thermogenesis ◽

Brown Adipose

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GPR120 controls neonatal brown adipose tissue thermogenic induction

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00081.2019 ◽

2019 ◽

Vol 317 (5) ◽

pp. E742-E750 ◽

Cited By ~ 2

Author(s):

Tania Quesada-López ◽

Aleix Gavaldà-Navarro ◽

Samantha Morón-Ros ◽

Laura Campderrós ◽

Roser Iglesias ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Receptor Protein ◽

Brown Adipocyte ◽

Fibroblast Growth Factor 21 ◽

Acid Oxidation ◽

Adaptive Thermogenesis ◽

Brown Adipose ◽

G Protein Coupled

Adaptive induction of thermogenesis in brown adipose tissue (BAT) is essential for the survival of mammals after birth. We show here that G protein-coupled receptor protein 120 (GPR120) expression is dramatically induced after birth in mouse BAT. GPR120 expression in neonatal BAT is the highest among GPR120-expressing tissues in the mouse at any developmental stage tested. The induction of GPR120 in neonatal BAT is caused by postnatal thermal stress rather than by the initiation of suckling. GPR120-null neonates were found to be relatively intolerant to cold: close to one-third did not survive at 21°C, but all such pups survived at 25°C. Heat production in BAT was significantly impaired in GPR120-null pups. Deficiency in GPR120 did not modify brown adipocyte morphology or the anatomical architecture of BAT, as assessed by electron microscopy, but instead impaired the expression of uncoupling protein-1 and the fatty acid oxidation capacity of neonatal BAT. Moreover, GPR120 deficiency impaired fibroblast growth factor 21 (FGF21) gene expression in BAT and reduced plasma FGF21 levels. These results indicate that GPR120 is essential for neonatal adaptive thermogenesis.

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