Autocrine negative feed-back regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Autocrine negative feed-back regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT. / Husted, Anna Sofie; Ekberg, Jeppe Hvidtfeldt; Tripp, Emma; Nissen, Tinne Amalie Damgaard; Meijnikman, Stijn; O'Brien, Shannon L; Ulven, Trond; Acherman, Yair; Bruin, Sjoerd C; Nieuwdorp, Max; Gerhart-Hines, Zach; Calebiro, Davide; Dragsted, Lars Ove; Schwartz, Thue W.

In: Molecular Metabolism, Vol. 42, 101103, 2020.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Husted, AS, Ekberg, JH, Tripp, E, Nissen, TAD, Meijnikman, S, O'Brien, SL, Ulven, T, Acherman, Y, Bruin, SC, Nieuwdorp, M, Gerhart-Hines, Z, Calebiro, D, Dragsted, LO & Schwartz, TW 2020, 'Autocrine negative feed-back regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT', Molecular Metabolism, vol. 42, 101103. https://doi.org/10.1016/j.molmet.2020.101103

APA

Husted, A. S., Ekberg, J. H., Tripp, E., Nissen, T. A. D., Meijnikman, S., O'Brien, S. L., ... Schwartz, T. W. (2020). Autocrine negative feed-back regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT. Molecular Metabolism, 42, [101103]. https://doi.org/10.1016/j.molmet.2020.101103

Vancouver

Husted AS, Ekberg JH, Tripp E, Nissen TAD, Meijnikman S, O'Brien SL et al. Autocrine negative feed-back regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT. Molecular Metabolism. 2020;42. 101103. https://doi.org/10.1016/j.molmet.2020.101103

Author

Husted, Anna Sofie ; Ekberg, Jeppe Hvidtfeldt ; Tripp, Emma ; Nissen, Tinne Amalie Damgaard ; Meijnikman, Stijn ; O'Brien, Shannon L ; Ulven, Trond ; Acherman, Yair ; Bruin, Sjoerd C ; Nieuwdorp, Max ; Gerhart-Hines, Zach ; Calebiro, Davide ; Dragsted, Lars Ove ; Schwartz, Thue W. / Autocrine negative feed-back regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT. In: Molecular Metabolism. 2020 ; Vol. 42.

Bibtex

@article{4b2ce72aa9c6420c8a2d33ba10e8eb75,
title = "Autocrine negative feed-back regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT",
abstract = "Objectives: Long chain fatty acids (LCFAs) released from adipocytes inhibit lipolysis through an unclear mechanism. We hypothesized that the LCFA receptor, FFAR4 (GPR120), which is highly expressed in adipocytes could be involved in this feed-back regulation.Methods and Results: LC-MS analysis of conditioned media from isoproterenol-stimulated primary cultures of murine and human adipocytes demonstrated that most of the released non-esterified free fatty acids (NEFAs) are known agonists for FFAR4. In agreement with this, conditioned medium from isoproterenol-treated adipocytes stimulated signaling strongly in FFAR4 transfected COS-7 cells as opposed to non-transfected control cells. In transfected 3T3-L1 cells, FFAR4 agonism stimulated Gi- and Go-mini G protein binding more strongly than Gq - effects which were blocked by the selective FFAR4 antagonist AH7614. In primary cultures of murine white adipocytes, the synthetic, selective FFAR4 agonist CpdA inhibited isoproterenol-induced intracellular cAMP accumulation in a manner similar to the antilipolytic control agent nicotinic acid acting through another receptor, HCAR2. In vivo, oral gavage with the synthetic, specific FFAR4 agonist CpdB decreased the level of circulating NEFAs in fasting lean mice to a similar degree as nicotinic acid. In agreement with the identified anti-lipolytic effect of FFAR4, plasma NEFAs and glycerol were increased in FFAR4 deficient mice as compared to littermate controls despite having elevated insulin levels; and, cAMP accumulation in primary adipocyte cultures was augmented by treatment with the FFAR4 antagonist conceivably by blocking the stimulatory tone of endogenous NEFAs on FFAR4.Conclusions: In white adipocytes FFAR4 functions as a NEFA-activated, autocrine, negative feed-back regulator of lipolysis by decreasing cAMP conceivably though Gi-mediated signaling.",
author = "Husted, {Anna Sofie} and Ekberg, {Jeppe Hvidtfeldt} and Emma Tripp and Nissen, {Tinne Amalie Damgaard} and Stijn Meijnikman and O'Brien, {Shannon L} and Trond Ulven and Yair Acherman and Bruin, {Sjoerd C} and Max Nieuwdorp and Zach Gerhart-Hines and Davide Calebiro and Dragsted, {Lars Ove} and Schwartz, {Thue W}",
note = "CURIS 2020 NEXS 359",
year = "2020",
doi = "10.1016/j.molmet.2020.101103",
language = "English",
volume = "42",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Autocrine negative feed-back regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT

AU - Husted, Anna Sofie

AU - Ekberg, Jeppe Hvidtfeldt

AU - Tripp, Emma

AU - Nissen, Tinne Amalie Damgaard

AU - Meijnikman, Stijn

AU - O'Brien, Shannon L

AU - Ulven, Trond

AU - Acherman, Yair

AU - Bruin, Sjoerd C

AU - Nieuwdorp, Max

AU - Gerhart-Hines, Zach

AU - Calebiro, Davide

AU - Dragsted, Lars Ove

AU - Schwartz, Thue W

N1 - CURIS 2020 NEXS 359

PY - 2020

Y1 - 2020

N2 - Objectives: Long chain fatty acids (LCFAs) released from adipocytes inhibit lipolysis through an unclear mechanism. We hypothesized that the LCFA receptor, FFAR4 (GPR120), which is highly expressed in adipocytes could be involved in this feed-back regulation.Methods and Results: LC-MS analysis of conditioned media from isoproterenol-stimulated primary cultures of murine and human adipocytes demonstrated that most of the released non-esterified free fatty acids (NEFAs) are known agonists for FFAR4. In agreement with this, conditioned medium from isoproterenol-treated adipocytes stimulated signaling strongly in FFAR4 transfected COS-7 cells as opposed to non-transfected control cells. In transfected 3T3-L1 cells, FFAR4 agonism stimulated Gi- and Go-mini G protein binding more strongly than Gq - effects which were blocked by the selective FFAR4 antagonist AH7614. In primary cultures of murine white adipocytes, the synthetic, selective FFAR4 agonist CpdA inhibited isoproterenol-induced intracellular cAMP accumulation in a manner similar to the antilipolytic control agent nicotinic acid acting through another receptor, HCAR2. In vivo, oral gavage with the synthetic, specific FFAR4 agonist CpdB decreased the level of circulating NEFAs in fasting lean mice to a similar degree as nicotinic acid. In agreement with the identified anti-lipolytic effect of FFAR4, plasma NEFAs and glycerol were increased in FFAR4 deficient mice as compared to littermate controls despite having elevated insulin levels; and, cAMP accumulation in primary adipocyte cultures was augmented by treatment with the FFAR4 antagonist conceivably by blocking the stimulatory tone of endogenous NEFAs on FFAR4.Conclusions: In white adipocytes FFAR4 functions as a NEFA-activated, autocrine, negative feed-back regulator of lipolysis by decreasing cAMP conceivably though Gi-mediated signaling.

AB - Objectives: Long chain fatty acids (LCFAs) released from adipocytes inhibit lipolysis through an unclear mechanism. We hypothesized that the LCFA receptor, FFAR4 (GPR120), which is highly expressed in adipocytes could be involved in this feed-back regulation.Methods and Results: LC-MS analysis of conditioned media from isoproterenol-stimulated primary cultures of murine and human adipocytes demonstrated that most of the released non-esterified free fatty acids (NEFAs) are known agonists for FFAR4. In agreement with this, conditioned medium from isoproterenol-treated adipocytes stimulated signaling strongly in FFAR4 transfected COS-7 cells as opposed to non-transfected control cells. In transfected 3T3-L1 cells, FFAR4 agonism stimulated Gi- and Go-mini G protein binding more strongly than Gq - effects which were blocked by the selective FFAR4 antagonist AH7614. In primary cultures of murine white adipocytes, the synthetic, selective FFAR4 agonist CpdA inhibited isoproterenol-induced intracellular cAMP accumulation in a manner similar to the antilipolytic control agent nicotinic acid acting through another receptor, HCAR2. In vivo, oral gavage with the synthetic, specific FFAR4 agonist CpdB decreased the level of circulating NEFAs in fasting lean mice to a similar degree as nicotinic acid. In agreement with the identified anti-lipolytic effect of FFAR4, plasma NEFAs and glycerol were increased in FFAR4 deficient mice as compared to littermate controls despite having elevated insulin levels; and, cAMP accumulation in primary adipocyte cultures was augmented by treatment with the FFAR4 antagonist conceivably by blocking the stimulatory tone of endogenous NEFAs on FFAR4.Conclusions: In white adipocytes FFAR4 functions as a NEFA-activated, autocrine, negative feed-back regulator of lipolysis by decreasing cAMP conceivably though Gi-mediated signaling.

U2 - 10.1016/j.molmet.2020.101103

DO - 10.1016/j.molmet.2020.101103

M3 - Journal article

C2 - 33091626

VL - 42

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

M1 - 101103

ER -

ID: 250253082