title: Genes implicated in insulin resistance are down-regulated in primary aldosteronism patients.
abstract: Primary aldosteronism (PA) patients display an increased incidence of insulin resistance. Herein we demonstrate the decreased gene expression of lipid metabolism genes PCK1, PLIN, ADIPOQ and PPARG in the visceral adipose tissue (VAT) of PA patients compared to age-, sex- and BMI-matched controls. In VAT, the expression of PCK1, PLIN, ADIPOQ and PPARG was inversely correlated with aldosterone levels; furthermore, PLIN and ADIPOQ gene expression was correlated with potassium levels. Therefore, raised aldosterone and low potassium may contribute to the reduced expression of these genes in PA patients. Finally, incubation of primary cultures of human adipocytes with aldosterone resulted in a decrease in the expression of PCK1, PLIN and ADIPOQ and this effect was blocked by eplerenone. Therefore, the characteristic aldosterone excess of PA patients may mediate the down-regulation of PCK1, PLIN and ADIPOQ in VAT that in turn may contribute to the insulin resistance observed in PA patients.
authors.affiliation: Division of Internal Medicine and Hypertension, Department of Medicine and Experimental Oncology, University of Torino, Torino, Italy.
authors.forename: Tracy Ann
authors.initials: TA
authors.lastname: Williams
authors.forename: Silvia
authors.initials: S
authors.lastname: Monticone
authors.forename: Riccardo
authors.initials: R
authors.lastname: Urbanet
authors.forename: Chiara
authors.initials: C
authors.lastname: Bertello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giraudo
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Francesco
authors.initials: F
authors.lastname: Fallo
authors.forename: Franco
authors.initials: F
authors.lastname: Veglio
authors.forename: Paolo
authors.initials: P
authors.lastname: Mulatero
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D000077545:Eplerenone; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance / Q000235:genetics*; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000070778:Perilipin-1; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000451:Mineralocorticoid Receptor Antagonists; D047495:PPAR gamma; D000070778:Perilipin-1; D010750:Phosphoproteins; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D011188:Potassium