Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

Johansen, Olivia Sveidahl; Ma, Tao; Hansen, Jakob Bondo; Markussen, Lasse K.; Schreiber, Renate; Reverte-Salisa, Laia; Dong, Hua; Christensen, Dan Ploug; Sun, Wenfei; Gnad, Thorsten; Karavaeva, Iuliia; Nielsen, Thomas S.; Kooijman, Sander; Cero, Cheryl; Dmytriyeva, Oksana; Shen, Ying; Razzoli, Maria; O’Brien, Shannon; Kuipers, Eline N.; Nielsen, Carsten H.; Orchard, William R.; Willemsen, Nienke; Jespersen, Naja Zenius; Lundh, Morten; Sustarsic, Elahu G.; Hallgren, Cecilie Mørch; Frost, Mikkel; McGonigle, Seth; Isidor, Marie S.; Broholm, Christa; Pedersen, Oluf; Grarup, Niels; Hansen, Torben; Kjær, Andreas; Granneman, James G.; Babu, M. Madan; Calebiro, Davide; Nielsen, Søren; Rydén, Mikael; Soccio, Raymond E.; Rensen, Patrick C.N.; Treebak, Jonas T.; Schwartz, Thue W.; Emanuelli, Brice; Bartolomucci, Alessandro; Pfeifer, Alexander; Zechner, Rudolf; Schéele, Camilla; Mandrup, Susanne; Gerhart‐Hines, Zachary

doi:10.1016/j.cell.2021.04.037

Cited by 73 publications

(62 citation statements)

References 90 publications

(145 reference statements)

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“…In tumor tissues, regulatory T cells (Tregs) undergo abnormal changes in expression, such as the change in LAG3 expression observed in classic Hodgkin lymphoma, upregulated LAYN expression in FOXP3 + Helios + Tregs, and changes in CCR8 and IL1R2 expression in HCC [ 134 , 135 ]. In addition, the chronic remodeling of tumor antigens alters Treg cell frequencies and subsequently promotes the recurrence of HCC [ 136 , 137 ].…”

Section: Applications Of Single-cell Sequencing In Cancer Biologymentioning

confidence: 99%

Applications of single-cell sequencing in cancer research: progress and perspectives

et al. 2021

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Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics sequencing, is a powerful tool to decipher the cellular and molecular landscape at a single-cell resolution, unlike bulk sequencing, which provides averaged data. The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. In this review, we summarize emerging single-cell sequencing technologies and recent cancer research progress obtained by single-cell sequencing, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and the underlying mechanisms of tumor biological behaviors. Overall, the prospects of single-cell sequencing in facilitating diagnosis, targeted therapy and prognostic prediction among a spectrum of tumors are bright. In the near future, advances in single-cell sequencing will undoubtedly improve our understanding of the biological characteristics of tumors and highlight potential precise therapeutic targets for patients.

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Section: Applications Of Single-cell Sequencing In Cancer Biologymentioning

confidence: 99%

Applications of single-cell sequencing in cancer research: progress and perspectives

et al. 2021

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“…The a-adrenergic receptor, Adra1a, is enriched in BAT Since much of adipocyte thermogenesis is regulated by the sympathetic nervous system through GPCR signaling in brown adipocytes 13,14,22 , we analyzed ribosomal pro ling data 23 to score GPCR mRNA expression based on two properties: (1) mRNA enrichment in brown adipose tissue (BAT) and (2) mRNA abundance in BAT (10% most abundant GPCRs). Four genes (Adra1a, Adrb1, Ptger1 and Cxcr7) ful lled these criteria (Extended Data Fig.…”

Section: Main Textmentioning

confidence: 99%

“…2e, f). Next, we carried out unilateral denervation of the interscapular BAT depot in which the right lobe was surgically denervated while the left lobe remained intact 22 . Strikingly, the cold-mediated elevation of Ckb, Alpl and Ppargc1a was blocked in the sympathetically denervated BAT lobes (Fig.…”

Section: Aar Signaling Regulates Futile Creatine Cycling Gene Expression In Batmentioning

confidence: 99%

Combined α- and β-adrenergic receptor activation triggers thermogenesis by the futile creatine cycle

Kazak

Rahbani

Scholtes

et al. 2022

Preprint

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Noradrenaline is the primary physiological regulator of adipocyte thermogenesis in response to decreased environmental temperature1. However, the molecular factors and effector pathways that lie downstream of noradrenaline-stimulated thermogenesis are still not fully understood but are purportedly driven by cAMP downstream of β-adrenergic receptor (βAR) activation. Furthermore, while the transcriptional mechanisms regulating Ucp1 are well-characterized2, the transcriptional regulation of UCP1-independent thermogenesis is largely unknown. Here, we show that brown adipose tissue (BAT) is primed to respond to environmental cold by triggering coordinated α-adrenergic receptor (αAR) and βAR signaling to induce the expression of thermogenic genes of the futile creatine cycle3,4. Using fat-specific loss-of-function models, we reveal that EBFs, ERRs, and PGC1α are required for the cold-stimulated transcriptional induction of the futile creatine cycle in vivo. Through the application of chemogenetics, we demonstrate that combined fat-selective Gαs (activated by βARs) and Gαq (activated by αARs) signaling elevates whole-body energy expenditure to a greater extent than either signaling pathway alone in a manner that is dependent on the key effector protein of the futile creatine cycle, CKB3. Moreover, genetic and pharmacological studies reveal that CKB is necessary for nearly all of the α1AR-stimulated component of brown adipocyte-intrinsic respiration and is thus critical for the full activation of noradrenaline-stimulated thermogenesis. Thus, the futile creatine cycle is integrated into facultative and adaptive thermogenesis through coordinated α1AR and β3AR signaling.

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“…Attention has been aroused by a recent experiment [ 51 ]. The experiment proposed that the relationship between lipolysis and WAT browning may be attributed to the existence of G protein-coupled receptor 3 (GPR3).…”

Section: Mechanism Of Exercise-mediated Browning Of Watmentioning

confidence: 99%

Exercise-Mediated Browning of White Adipose Tissue: Its Significance, Mechanism and Effectiveness

Zhu

Chen

et al. 2021

IJMS

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As a metabolic organ, adipose tissue plays an important role in regulating metabolism. In adults, most adipose tissue is white adipose tissue (WAT), and excessive expansion of WAT will lead to obesity. It is worth noting that exercise can reduce the fat mass. There is also a lot of evidence that exercise can promote the browning of WAT, which is beneficial for metabolic homeostasis. Multiple factors, including reactive oxygen species (ROS), metabolites, nervous system, exerkines and lipolysis can facilitate exercise-mediated browning of WAT. In this review, the roles and the underlying mechanisms of exercise-mediated browning of WAT are summarized. The effects of different styles of exercise on the browning of WAT are also discussed, with the aim to propose better exercise strategies to enhance exercise-mediated browning of WAT, so as to promote metabolic health. Finally, the different reactivity of WAT at different anatomical sites to exercise-mediated browning is reviewed, which may provide potential suggestion for people with different fat loss needs.

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Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

Cited by 73 publications

References 90 publications

Applications of single-cell sequencing in cancer research: progress and perspectives

Applications of single-cell sequencing in cancer research: progress and perspectives

Combined α- and β-adrenergic receptor activation triggers thermogenesis by the futile creatine cycle

Exercise-Mediated Browning of White Adipose Tissue: Its Significance, Mechanism and Effectiveness

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