Regulation of leptin receptor expression in human polarized Caco-2/15 cells.
BACKGROUND
Leptin receptors (LEPR) are expressed in intestinal epithelial cells from the duodenum to the colon. Since their role is fundamental for the proper control of nutrient absorption, mucus secretion and mucosa renewal, the regulation of LEPR expression is for the first time investigated as a function of various potential effectors.


RESULTS
Fully differentiated Caco-2/15 cells were incubated for 24 hours with nutrients [carbohydrates, fatty acids (FA), amino acids and sterols], hormones (leptin, insulin, hydrocortisone and epithelial growth factor), inflammatory agents (Interferon-γ, LPS, TNF-α), and PPAR agonists (rosiglitazone and WY14643). Levels of LEPR mRNA and protein expressions were measured by RT-PCR and Western blots, respectively.


RESULTS
Long (219.1) and short (219.3) isoforms of the LEPR were detected in Caco-2/15 cells, while absence of the isoform 219.2 was noted. Their gene expression was modulated by carbohydrates, FA, PPAR agonists, biliary salts, insulin and leptin itself. On the other hand, LEPR protein expression was modulated by FA, cholesterol, biliary salts, PPAR agonists and insulin. Interestingly, the same effectors may have opposite effects on the short and the long LEPR isoforms, as well as on mRNA and protein levels. Finally, Caco-2/15 cells were found to be sensitive to the effector location, i.e. apical or basolateral compartment.


CONCLUSIONS
Our results suggest that (i) the expression of LEPR in Caco-2/15 cell line is not constitutive; (ii) the agents present in the apical or basolateral medium have different effects on LEPR mRNA and/or protein levels; and (iii) short and long isoforms of LEPR follow different patterns of regulation.
Research Centre, CHU Ste-Justine, Montreal (Quebec), Canada, H3T 1C5.
Philippe G
PG
Cammisotto
Moise
M
Bendayan
Emile
E
Levy
D000596:Amino Acids / Q000494:pharmacology; D018938:Caco-2 Cells; D002241:Carbohydrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics*; D002784:Cholesterol / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D020033:Protein Isoforms; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics* / Q000378:metabolism
D000596:Amino Acids; D002241:Carbohydrates; D005227:Fatty Acids; C515448:LEPR protein, human; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D054411:Receptors, Leptin; D002784:Cholesterol