Differential regulation of glyceroneogenesis by glucocorticoids in epididymal and retroperitoneal white adipose tissue from rats

Endocrine. 2017 Aug;57(2):287-297. doi: 10.1007/s12020-017-1315-4. Epub 2017 May 29.

Abstract

Purpose: Investigate the glycerol-3-phosphate generation pathways in epididymal (EPI) and retroperitoneal (RETRO) adipose tissues from dexamethasone-treated rats.

Methods: Rats were treated with dexamethasone for 7 days. Glycerol-3-phosphate generation pathways via glycolysis, glyceroneogenesis and direct phosphorylation of glycerol were evaluated, respectively, by 2-deoxyglucose uptake, phosphoenolpyruvate carboxykinase (PEPCK-C) activity and pyruvate incorporation into triacylglycerol (TAG)-glycerol, and glycerokinase activity and glycerol incorporation into TAG-glycerol.

Results: Dexamethasone treatment markedly decreased the body weight, but increased the weight and lipid content of EPI and RETRO and plasma insulin, glucose, non-esterified fatty acid and TAG levels. EPI and RETRO from dexamethasone-treated rats showed increased rates of de novo fatty acid synthesis (80 and 100%) and basal lipolysis (20%). In EPI, dexamethasone decreased the 2-deoxyglucose uptake (50%), as well as glyceroneogenesis, evidenced by a decrease of PEPCK-C activity (39%) and TAG-glycerol synthesis from pyruvate (66%), but increased the glycerokinase activity (50%) and TAG-glycerol synthesis from glycerol (72%) in this tissue. In spite of a similar reduction in 2-deoxyglucose uptake in RETRO, dexamethasone treatment increased glyceroneogenesis, evidenced by PEPCK activity (96%), and TAG-glycerol synthesis from pyruvate (110%), accompanied by a decrease in glycerokinase activity (50%) and TAG-glycerol synthesis from glycerol (50%). Dexamethasone effects on RETRO were accompanied by a decrease in p-Akt content and by lower insulin effects on the rates of glycerol release in the presence of isoproterenol and on the rates of glucose uptake in isolated adipocytes.

Conclusion: Our data demonstrated differential regulation of glyceroneogenesis and direct phosphorylation of glycerol by glucocorticoids in EPI and RETRO from rats.

Keywords: Adipose tissue; Glucocorticoids; Glycerokinase; Glyceroneogenesis.

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism*
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism*
  • Adiposity / drug effects
  • Animals
  • Body Weight / drug effects
  • Dexamethasone / pharmacology*
  • Epididymis / drug effects
  • Epididymis / metabolism*
  • Glucocorticoids / pharmacology*
  • Glycerol / metabolism*
  • Glycerol Kinase / biosynthesis
  • Intra-Abdominal Fat / drug effects*
  • Intra-Abdominal Fat / metabolism*
  • Intracellular Signaling Peptides and Proteins / biosynthesis
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lipolysis / drug effects
  • Male
  • Organ Size / drug effects
  • Phosphoenolpyruvate Carboxykinase (GTP) / biosynthesis
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics
  • Rats
  • Rats, Wistar
  • Retroperitoneal Space
  • Triglycerides / biosynthesis

Substances

  • Glucocorticoids
  • Intracellular Signaling Peptides and Proteins
  • Triglycerides
  • Dexamethasone
  • Glycerol Kinase
  • Pck1 protein, rat
  • Phosphoenolpyruvate Carboxykinase (GTP)
  • Glycerol