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Establishing the potency of N-acyl amino acids versus conventional fatty acids as thermogenic uncouplers in cells and mitochondria from different tissues
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Northwest A&F University, China.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.ORCID-id: 0000-0002-2915-6450
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.ORCID-id: 0000-0001-6107-5047
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.ORCID-id: 0000-0001-6594-2363
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Antal upphovsmän: 62022 (Engelska)Ingår i: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1863, nr 4, artikel-id 148542Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The possibility that N-acyl amino acids could function as brown or brite/beige adipose tissue-derived lipokines that could induce UCP1-independent thermogenesis by uncoupling mitochondrial respiration in several peripheral tissues is of significant physiological interest. To quantify the potency of N-acyl amino acids versus conventional fatty acids as thermogenic inducers, we have examined the affinity and efficacy of two pairs of such compounds: oleate versus N-oleoyl-leucine and arachidonate versus N-arachidonoyl-glycine in cells and mitochondria from different tissues. We found that in cultures of the muscle-derived L6 cell line, as well as in primary cultures of murine white, brite/beige and brown adipocytes, the N-acyl amino acids were proficient uncouplers but that they did not systematically display higher affinity or potency than the conventional fatty acids, and they were not as efficient uncouplers as classical protonophores (FCCP). Higher concentrations of the N-acyl amino acids (as well as of conventional fatty acids) were associated with signs of deleterious effects on the cells. In liver mitochondria, we found that the N-acyl amino acids uncoupled similarly to conventional fatty acids, thus apparently via activation of the adenine nucleotide transporter-2. In brown adipose tissue mitochondria, the N-acyl amino acids were able to activate UCP1, again similarly to conventional fatty acids. We thus conclude that the formation of the acyl-amino acid derivatives does not confer upon the corresponding fatty acids an enhanced ability to induce thermogenesis in peripheral tissues, and it is therefore unlikely that the N-acyl amino acids are of specific physiological relevance as UCP1-independent thermogenic compounds.

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2022. Vol. 1863, nr 4, artikel-id 148542
Nyckelord [en]
Adenine nucleotide transporter, Fatty acids, N-acyl amino acids, Nonshivering thermogenesis, Uncoupling protein-1, N-oleoyl-leu, N-arachidonoyl-gly
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Biologiska vetenskaper
Identifikatorer
URN: urn:nbn:se:su:diva-204413DOI: 10.1016/j.bbabio.2022.148542ISI: 000781771000002PubMedID: 35192808OAI: oai:DiVA.org:su-204413DiVA, id: diva2:1655954
Tillgänglig från: 2022-05-04 Skapad: 2022-05-04 Senast uppdaterad: 2022-05-04Bibliografiskt granskad

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Gao, YunShabalina, Irina G.Braz, G. Ruda F.Cannon, BarbaraNedergaard, Jan

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Gao, YunShabalina, Irina G.Braz, G. Ruda F.Cannon, BarbaraNedergaard, Jan
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