Effects of rilpivirine, 17β-estradiol and β-naphthoflavone on the inflammatory status of release of adipocytokines in 3T3-L1 adipocytes in vitro

Abstract

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor, recently developed as a drug of choice for initial anti-retroviral (ARV) treatment of HIV-1 infection, whereas estradiol is a major component of hormonal contraceptives. Both drugs have effects on lipid metabolism, impairment of adipocyte differentiation and alteration of adipose tissue distribution and function. This study investigated the effects of different concentrations of either rilpivirine or estradiol either alone or in combination on adipocyte differentiation and adipocytokines status in vitro in the absence and presence of β-naphthoflavone, (BNF),a potent agonist of the aryl hydrocarbon receptor. 3T3-L1 human pre-adipocytes were cultured and differentiated with different concentrations of treatment drugs. After 10 days of differentiation procedure, cells were examined for their morphology and viability. Glycerol,adiponectin, leptin, resistin and interleukin-8 (IL-8) were quantified using commercially available kits. The results show that either rilpivirine or estradiol individually or during their combination can evoke significant increases in glycerol release and a concomitant significant decrease of adiponectin from adipocytes. These effects were dose-dependent. The effects of combined treatments were much larger than individual concentration for each drug. Both drugs had little of no effect on leptin levels, except for a small decrease with 10 µM rilpivirine alone or when combined with estradiol. In addition, both drugs evoked small increases in the release of resistin and interleukin-8 with significant values at higher doses compared to untreated adipocytes.When adipocytes were pretreated with BNF, either rilpivirine or, estradiol or when combined evoked a much larger release in glycerol and a much larger decrease in adiponectin compared to the absence of BNF. In contrast, BNF pretreatment had little of no effect on either leptin, resistin or IL-8 metabolism compared to the results obtained in the presence of either rilpivirine or estradiol alone or in combination.These results show that rilpivirine and estradiol either alone or when combined or pretreated with BNF can evoke marked effects on glycerol and cytokines levels from adipocytes. However, their mechanism (s) in inducing adipogenesis warrants further investigation of different transcription factors at gene expression levels.

Natural and Synthetic Estrogens in Chronic Inflammation and Breast Cancer

“…In contrast with leptin, adiponectin consistently shows anti-inflammatory effects in a number of studies, converging at the mechanism that adiponectin suppresses the production of TNF-α and IFN γ by negatively regulating macrophages and dendritic cells and inhibiting NF-κB activation [ 95 , 96 , 97 ]. While the expression and secretion of adiponectin are inhibited by TNFα and IL-6 as a counteraction from proinflammatory components [ 98 ], it is interesting to find that estradiol suppresses adiponectin but not leptin expression in 3T3-L1 adipocyte cell line [ 99 ] and that serum adiponectin level is negatively correlated with estradiol level in postmenopausal women, thus bringing up the hypothesis that estrogen may antagonize the anti-inflammatory effect of adiponectin [ 100 ]. Taken together, this explains the clinical observation that the increased levels of leptin and decreased adiponectin secretion are directly associated with breast cancer development [ 101 ].…”

Anti-obesity effects of red pepper (Capsicum annuum L.) leaf extract on 3T3-L1 preadipocytes and high fat diet-fed mice

“…It acts as a hormone and plays an important role in modulating glucose and lipid metabolism as an insulin-sensitizing adipocytokine. 18 PLE treatment suppressed the release of adiponectin during differentiation. These results showed that PLE decreased lipid accumulation and the adiponectin concentration.…”

“…It acts as a hormone and plays an important role in modulating glucose and lipid metabolism as an insulin-sensitizing adipocytokine. 18…”