Relaxin has beneficial effects on liver lipidome and metabolic enzymes.
Animals
Cell Line, Tumor
Delta-5 Fatty Acid Desaturase
Fatty Acid Desaturases
/ metabolism
Fatty Acids
/ metabolism
Fatty Acids, Monounsaturated
/ metabolism
Fatty Acids, Omega-3
/ metabolism
Glycerophospholipids
/ metabolism
Hep G2 Cells
Homeostasis
/ drug effects
Humans
Lipidomics
/ methods
Liver
/ drug effects
Male
Metabolome
/ drug effects
Phosphatidylethanolamine N-Methyltransferase
/ metabolism
Phosphatidylethanolamines
/ metabolism
Rats
Rats, Sprague-Dawley
Recombinant Proteins
/ pharmacology
Relaxin
/ pharmacology
desaturases
liver
lysoglycerophospholipids
metabolomics
relaxin
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
27
05
2021
received:
11
12
2020
accepted:
02
06
2021
entrez:
18
6
2021
pubmed:
19
6
2021
medline:
17
7
2021
Statut:
ppublish
Résumé
Relaxin is an insulin-like hormone with pleiotropic protective effects in several organs, including the liver. We aimed to characterize its role in the control of hepatic metabolism in healthy rats. Sprague-Dawley rats were treated with human recombinant relaxin-2 for 2 weeks. The hepatic metabolic profile was analyzed using UHPLC-MS platforms. Hepatic gene expression of key enzymes of desaturation (Fads1/Fads2) of n-6 and n-3 polyunsaturated fatty acids (PUFAs), of phosphatidylethanolamine (PE) N-methyltransferase (Pemt), of fatty acid translocase Cd36, and of glucose-6-phosphate isomerase (Gpi) were quantified by Real Time-PCR. Activation of 5'AMP-activated protein kinase (AMPK) was analyzed by Western Blot. Relaxin-2 significantly modified the hepatic levels of 19 glycerophospholipids, 2 saturated (SFA) and 1 monounsaturated (MUFA) fatty acids (FA), 3 diglycerides, 1 sphingomyelin, 2 aminoacids, 5 nucleosides, 2 nucleotides, 1 carboxylic acid, 1 redox electron carrier, and 1 vitamin. The most noteworthy changes corresponded to the substantially decreased lysoglycerophospholipids, and to the clearly increased FA (16:1n-7/16:0) and MUFA + PUFA/SFA ratios, suggesting enhanced desaturase activity. Hepatic gene expression of Fads1, Fads2, and Pemt, which mediates lipid balance and liver health, was increased by relaxin-2, while mRNA levels of the main regulator of hepatic FA uptake Cd36, and of the essential glycolysis enzyme Gpi, were decreased. Relaxin-2 augmented the hepatic activation of the hepatoprotector and master regulator of energy homeostasis AMPK. Relaxin-2 treatment also rised FADS1, FADS2, and PEMT gene expression in cultured Hep G2 cells. Our results bring to light the hepatic metabolic features stimulated by relaxin, a promising hepatoprotective molecule.
Identifiants
pubmed: 34143495
doi: 10.1096/fj.202002620RR
doi:
Substances chimiques
Delta-5 Fatty Acid Desaturase
0
Fatty Acids
0
Fatty Acids, Monounsaturated
0
Fatty Acids, Omega-3
0
Glycerophospholipids
0
Phosphatidylethanolamines
0
Recombinant Proteins
0
phosphatidylethanolamine
39382-08-6
Relaxin
9002-69-1
Fatty Acid Desaturases
EC 1.14.19.-
FADS1 protein, human
EC 1.14.19.3
Phosphatidylethanolamine N-Methyltransferase
EC 2.1.1.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21737Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
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