Year: 2018
Type: article
Abstract: Introduction: Obesity is a major cause of morbidity and mortality globally.Understanding the mechanisms linking obesity to morbidity and the role of adipose tissue in human metabolism is essential to combat this threat.Research shows that the second messenger cyclic adenosine monophosphate (cAMP) can be released by the liver and exert endocrine effects on renal tubule cells causing natriuretic and phosphaturic effects.Extracellular cAMP has also been shown increase fatty acid oxidation in hepatocytes.This urged us to investigate the possible regulatory effect of extracellular cAMP on adipose tissue metabolism.Objective: To test whether extracellular cAMP affects lipolysis in adipocytes Methods: 3T3-L1 cells were cultured and differentiated into mature adipocytes using conventional methods and thereafter exposed to different cAMP concentrations for three hours.Effects from blockage of cAMP degradation was tested by adding the ecto-5'nucleotidase inhibitor AMP-CP.Glycerol released into the medium was quantified as a marker of lipolysis.All data were normalized to intracellular protein levels to avoid possible variation from uneven adipocyte distribution between culture wells.Results: cAMP increased lipolysis at a concentration of 200nM.At lower concentrations of cAMP (between 1-100nM), lipolysis was instead decreased or unchanged.AMP-CP, either alone or in combination with 200nM, had no effect on lipolysis, Conclusion/Discussion: These results suggest that cAMP both can stimulate and inhibit lipolysis.One possibility is that extracellular cAMP is converted to adenosine, which in turn activates adenosine receptors A1 and A2a expressed on adipocytes.Adenosine receptor A1 inhibits lipolysis whereas A2a stimulates lipolysis.A1 receptors are more abundant in adipocytes and may therefore require lower concentrations to cause this anti-lipolytic effect, while A2a may be more potent overruling the effect of A1 at higher concentrations.Alternatively, cAMP affects lipolysis directly through a yet unknown receptor.
Author: Jonathan Terling
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3042137643