Humoral Regulation of Resistin Expression in 3T3-L1 and Mouse Adipose Cells

Abstract

Resistin is a hormone secreted by adipocytes that acts on skeletal muscle myocytes, hepatocytes, and adipocytes themselves, reducing their sensitivity to insulin. In the present study, we investigated how the expression of resistin is affected by glucose and by mediators known to affect insulin sensitivity, including insulin, dexamethasone, tumor necrosis factor-␣ (TNF-␣), epinephrine, and somatropin. We found that resistin expression in 3T3-L1 adipocytes was significantly upregulated by high glucose concentrations and was suppressed by insulin. Dexamethasone increased expression of both resistin mRNA and protein 2.5-to 3.5-fold in 3T3-L1 adipocytes and by ϳ70% in white adipose tissue from mice. In contrast, treatment with troglitazone, a thiazolidinedione antihyperglycemic agent, or TNF-␣ suppressed resistin expression by ϳ80%. Epinephrine and somatropin were both moderately inhibitory, reducing expression of both the transcript and the protein by 30 -50% in 3T3-L1 adipocytes. Taken together, these data make it clear that resistin expression is regulated by a variety of hormones and that cytokines are related to glucose metabolism. Furthermore, they suggest that these factors affect insulin sensitivity and fat tissue mass in part by altering the expression and eventual secretion of resistin from adipose cells.

Regulation of adipocytokines and insulin resistance

“…Furthermore, it is not clear whether PPARγ-agonists consistently suppress resistin gene expression (Table 1). In accordance with the original observations, PPARγ-activators such as troglitazone, rosiglitazone, and darglitazone potently down-regulate resistin mRNA by approximately 80% to 90% in 3T3-L1 adipocytes in vitro [65,66] and resistin mRNA is down-regulated by 72% in db/db mice after rosiglitazone treatment [67]. In contrast, up-regulation of resistin mRNA expression has been observed after treatment of male ob/ob mice and ZDF rats with the PPARγ-agonists MC-555, rosiglitazone, and GW1929 for 7 days [60].…”

“…Because β-adrenergic activation is a potent activator of lipolysis in fat cells and NEFA inhibit resistin gene expression in rat adipocytes, β-adrenoceptor stimulation might mediate its inhibitory effect via increased NEFA concentrations [62]. Down-regulation of resistin mRNA and protein by β-adrenergic activation has been confirmed in one study [65], whereas recently, down-regulation of this adipocytokine only by forskolin but not by isoproterenol has been reported [66]. Furthermore, insulin down-regulates resistin gene expression in 3T3-L1 adipocytes in vitro (Table 1) [65,66].…”

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

“…Glucocorticoids and insulin are associated with the expression of some genes through the Sp1 function [36]. The expression of resistin is regulated by several factors, including glucose, insulin, dexamethasone and thiazolidinediones [17]. Therefore, it would be interesting to investigate whether Sp1 is involved in any transcriptional regulation of the gene caused by these treatments.…”

“…Many studies show that various hormones and drugs influencing insulin sensitivity regulate resistin mRNA expression in cell culture and animal models [14][15][16][17]. Glucose and dexamethasone increase resistin mRNA levels, but insulin, TNF-α and thiazolidinediones suppress the expression of resistin.…”

Impaired glucose tolerance is accompanied by decreased insulin sensitivity in tissues of mice implanted with cells that overexpress resistin

“…An agent which causes insulin resistance, TNF-α, negatively regulated the expression and secretion of resistin in cultured adipocytes [9,10]. The bioactive action of resistin is mediated by the regulation of other adipocyte-derived factors and/or their direct competitive or co-ordinate interaction in target tissues [11].…”