Transgenic female mice producing trans 10, cis 12-conjugated linoleic acid present excessive prostaglandin E2, adrenaline, corticosterone, glucagon, and FGF21

Sci Rep. 2024 May 30;14(1):12430. doi: 10.1038/s41598-024-63282-7.

Abstract

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.

Keywords: Adipose; Conjugated linoleic acid; Energy expenditure; Inflammation; Steatosis.

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adiposity / drug effects
  • Animals
  • Corticosterone* / metabolism
  • Dinoprostone* / metabolism
  • Epinephrine* / metabolism
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Female
  • Fibroblast Growth Factors* / genetics
  • Fibroblast Growth Factors* / metabolism
  • Glucagon* / metabolism
  • Hypertriglyceridemia / genetics
  • Hypertriglyceridemia / metabolism
  • Linoleic Acids, Conjugated* / metabolism
  • Linoleic Acids, Conjugated* / pharmacology
  • Lipid Metabolism / drug effects
  • Lipolysis / drug effects
  • Male
  • Mice
  • Mice, Transgenic*
  • Thermogenesis / drug effects
  • Thermogenesis / genetics

Substances

  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Linoleic Acids, Conjugated
  • Corticosterone
  • Dinoprostone
  • Glucagon
  • Epinephrine