Glucagon-like peptide 1 (GLP-1)-based therapy upregulates LXR-ABCA1/ABCG1 cascade in adipocytes

Ahmed M. Mostafa, Nadia M. Hamdy, Hala O. El-Mesallamy, Sherif Abdel-Rahman

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A promising treatment for obesity involves the use of therapeutic agents that increase the level of the glucagon-like peptide (GLP-1) which reduces appetite and food intake. Native GLP-1 is rapidly metabolized by the dipeptidyl peptidase-4 (DPP-4) enzyme and, as such, GLP-1 mimetics or DPP-4 inhibitors represent promising treatment approaches. Interestingly, obese patient receiving such medications showed improved lipid profiles and cholesterol homeostasis, however the mechanism(s) involved are not known. Members of the ATP-binding cassette (ABC) transporters, including ABCA1 and ABCG1, play essential roles in reverse cholesterol transport and in high density lipoprotein (HDL) formation. These transporters are under the transcriptional regulation of liver X receptor alpha (LXR-α). We hypothesize that GLP-1 mimetics and/or DPP-4 inhibitors modulate ABCA1/ABCG1 expression in adipocytes through an LXR-α mediated process and thus affecting cholesterol homeostasis. 3T3-L1 adipocytes were treated with the DPP-4 inhibitor vildagliptin (2 nM) or the GLP-1 mimetic exendin-4 (5 nM). Gene and protein expression of ABCA1, ABCG1 and LXR-α were determined and correlated with cholesterol efflux. Expression levels of interleukin-6 (IL-6), leptin and the glucose transporter-4 (GLUT-4) were also determined. Treatment with both medications significantly increased the expression of ABCA1, ABCG1, LXR-α and GLUT-4, decreased IL-6 and leptin, and improved cholesterol efflux from adipocytes (P <0.05). Our data suggest that GLP-1-based therapy modulate ABCA1/ABCG1 expression in adipocytes potentially through an LXR-α mediated process.

Original languageEnglish (US)
Pages (from-to)900-905
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume468
Issue number4
DOIs
StatePublished - Dec 25 2015

Fingerprint

Glucagon-Like Peptide 1
Adipocytes
Liver
Up-Regulation
Dipeptidyl-Peptidase IV Inhibitors
Cholesterol
Facilitative Glucose Transport Proteins
Leptin
Interleukin-6
Homeostasis
Therapeutics
Glucagon-Like Peptides
Dipeptidyl Peptidase 4
ATP-Binding Cassette Transporters
Therapeutic Uses
Appetite
HDL Lipoproteins
Liver X Receptors
Obesity
Eating

Keywords

  • ABC transporters
  • Adipocytes
  • Cholesterol
  • DPP-4 inhibitor
  • GLP-1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Glucagon-like peptide 1 (GLP-1)-based therapy upregulates LXR-ABCA1/ABCG1 cascade in adipocytes. / Mostafa, Ahmed M.; Hamdy, Nadia M.; El-Mesallamy, Hala O.; Abdel-Rahman, Sherif.

In: Biochemical and Biophysical Research Communications, Vol. 468, No. 4, 25.12.2015, p. 900-905.

Research output: Contribution to journalArticle

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