Glucose enhances catecholamine-stimulated lipolysis via increased glycerol-3-phosphate synthesis in 3T3-L1 adipocytes and rat adipose tissue

Mol Biol Rep. 2021 Sep;48(9):6269-6276. doi: 10.1007/s11033-021-06617-1. Epub 2021 Aug 10.

Abstract

Background: During lipolysis, triglyceride (TG) are hydrolyzed into a glycerol and fatty acids in adipocyte. A significant portion of the fatty acids are re-esterificated into TG, and this is a critical step in promoting lipolysis. Although glycerol-3-phosphate (G3P) is required for triglyceride synthesis in mammalian cell, the substrate for G3P synthesis during active lipolysis is not known. A recent study showed that the inhibition of glucose uptake reduces catecholamine-stimulated lipolysis, suggesting that glucose availability is important in lipolysis in adipocytes. We hypothesized that glucose might play an essential role in generating G3P and thereby promoting catecholamine-stimulated lipolysis in adipocytes. Therefore, we determined the effect of glucose availability on catecholamine-stimulated lipolysis in 3T3-L1 adipocytes and rat adipose tissue.

Methods and results: 3T3-L1 adipocytes and rat epididymal fat pads were cultured in a medium with/without glucose during stimulation by isoproterenol. Glycerol release was higher when adipocytes were cultured in a glucose-containing medium than that in a medium without glucose. Measurement of glucose uptake during catecholamine-stimulated lipolysis showed a slight, but significant increase in glucose uptake. We also compared glucose metabolism-related protein, such as glucose transporter 4, hexokinase, glycerol-3-phosphate dehydrogenase and lipase contents between fat tissues that play a critical role in active lipolysis. Epididymal fat exhibited higher lipolytic activity than inguinal fat because of higher lipase and glucose metabolism-related protein contents.

Conclusion: We demonstrated that catecholamine-stimulated lipolysis is enhanced in the presence of glucose, and suggests that glucose is one of the primary substrates for G3P in adipocytes during active lipolysis.

Keywords: Fat; Glucose uptake; Glycerol; Isoproterenol.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Adipose Tissue / metabolism*
  • Animals
  • Catecholamines / pharmacology*
  • Culture Media / chemistry
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Glucose / pharmacology*
  • Glycerol / metabolism
  • Glycerophosphates / biosynthesis*
  • Isoproterenol / pharmacology
  • Lipase / metabolism
  • Lipolysis / drug effects*
  • Male
  • Mice
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Triglycerides / metabolism

Substances

  • Catecholamines
  • Culture Media
  • Fatty Acids
  • Glycerophosphates
  • Triglycerides
  • alpha-glycerophosphoric acid
  • Lipase
  • Glucose
  • Isoproterenol
  • Glycerol