Relaxin has beneficial effects on liver lipidome and metabolic enzymes

FASEB J. 2021 Jul;35(7):e21737. doi: 10.1096/fj.202002620RR.


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.

Keywords: desaturases; liver; lysoglycerophospholipids; metabolomics; relaxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Liver / enzymology*
  • Liver / metabolism
  • Male
  • Metabolome / drug effects
  • Phosphatidylethanolamine N-Methyltransferase / metabolism
  • Phosphatidylethanolamines / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Relaxin / pharmacology*


  • Delta-5 Fatty Acid Desaturase
  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Fatty Acids, Omega-3
  • Glycerophospholipids
  • Phosphatidylethanolamines
  • Recombinant Proteins
  • phosphatidylethanolamine
  • Relaxin
  • Fatty Acid Desaturases
  • FADS1 protein, human
  • Phosphatidylethanolamine N-Methyltransferase