title: Endothelin-1 inhibits resistin secretion in 3T3-L1 adipocytes.
abstract: Resistin is an adipocyte-derived hormone whose role in the development of insulin resistance is controversial. Endothelin-1 (ET-1) is a 21 amino acid peptide demonstrated to possess vasoconstrictor, positive inotropic, mitogenic, and metabolic properties. In numerous disease states, including congestive heart failure, obesity, and diabetes, elevated levels of ET-1 have been reported and are thought to contribute to the pathology of the disease. A recent study demonstrated that ET-1 induces the expression and stimulates the secretion of the adipose tissue-derived hormone leptin. However, the effect of ET-1 on resistin secretion has not been determined. To characterize the effect of ET-1 on resistin secretion, 3T3-L1 fibroblasts were differentiated into adipocytes and allowed to mature for 14 days. Cells were incubated for 24h with ET-1 (1-100 nM), insulin (1-100 nM), insulin+ET-1 (100 nM I+E) or the appropriate vehicle or antagonist. At the end of the incubation period, resistin secretion was determined in the media by immunoblotting and densitometric analysis. ET-1 (1-100 nM) significantly decreased basal resistin secretion by 49% (1 nM), 43% (10nM), and 59% (100 nM). Insulin (1-100 nM) produced a concentration-dependent increase in resistin secretion from 3T3-L1 adipocytes (1 nM-42%, 10nM-55%, and 100 nM-86% vs. control). Insulin-stimulated resistin secretion (100 nM) was almost completely inhibited (94%) by ET-1 (100 nM). The effects of ET-1 on resistin protein secretion were inhibited by co-incubation with the ET(A) receptor antagonist BQ-610. In conclusion, our studies demonstrate that basal and hormonal stimulation of resistin secretion by insulin are inhibited by ET-1. Such findings demonstrate that resistin secretion is regulated in a similar manner to other adipose tissue factors, including leptin, in 3T3-L1 adipocytes. In addition, our findings suggest that vascular factors such as ET-1 may regulate whole body energy metabolism through adipocyte-derived hormones, including leptin and resistin.
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, 219 Greene Hall, Auburn, AL 36849-5518, USA.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhong
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Clarke
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kemppainen
authors.forename: Dean D
authors.initials: DD
authors.lastname: Schwartz
authors.forename: Robert L
authors.initials: RL
authors.lastname: Judd
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism*; D006729:Hormones, Ectopic / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D020932:Nerve Growth Factor; D009842:Oligopeptides / Q000494:pharmacology; D011506:Proteins; D052243:Resistin; D013997:Time Factors
chemical_list: D019332:Endothelin-1; D006729:Hormones, Ectopic; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D011506:Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D052243:Resistin; C499623:Retn protein, mouse; C413576:Retnla protein, mouse; C087220:BQ 610; D020932:Nerve Growth Factor