Abstract
In the search for new drugs against obesity, the chronic disease that threatens human health worldwide, several works have focused on the study of estrogen homologs because of the role of estrogen receptors (ERs) in adipocyte growth. The isoflavone equol, an ERβ agonist, has shown beneficial metabolic effects in in vivo and in vitro assays; however, additional studies are required to better characterize its potential for body weight control. Here, we showed that the treatment of 3T3-L1 cells with 10 μM of S-equol for the first three days of the adipocyte differentiation protocol was able to prevent cells becoming semi-rounded and having a lipid droplet formation until the seventh day of culture; moreover, lipid accumulation was reduced by about 50%. Congruently, S-equol induced a reduction in mRNA expression of the adipogenic markers C/EBPα and PPARγ, and adipokines secretion, mainly Adiponectin, Leptin, Resistin, and MCP-1, while the release of PAI-1 was augmented. Moreover, it also reduced the expression of ERα and attenuated the subexpression of ERβ associated with adipogenesis. Altogether, our data suggested that S-equol binding to ERβ affects the transcriptional program that regulates adipogenesis and alters adipocyte functions. Future efforts will focus on studying the impact of S-equol on ER signaling pathways.
Highlights
Obesity and overweight have become one of the main health problems worldwide because they increase the risk of suffering from diabetes, hypertension, cancer, and other diseases associated with the metabolic syndrome [1]
Obesity is associated with an abnormal expansion of adipose tissue and a deregulation of the adipogenesis process [2], which affects the synthesis of adipokines, such as Leptin, Adiponectin, Resistin, Plasminogen activator inhibitor (PAI-1), Monocyte chemoattractant protein 1 (MCP-1), Interleukin-6 (IL-6), and Tumor necrosis factor alpha (TNFα), with autocrine and paracrine functions in inflammation, homeostasis regulation, and adipogenesis, among other processes [3,4]
Experiments in 3T3-L1 preadipocytes and adipose tissue from obese mice showed that ERα regulates insulin sensitivity and glucose tolerance, while ERβ modulates the expression of genes related to adipogenesis by inhibiting the function of the pro-adipogenic marker PPARγ [7]
Summary
Obesity and overweight have become one of the main health problems worldwide because they increase the risk of suffering from diabetes, hypertension, cancer, and other diseases associated with the metabolic syndrome [1]. Obesity is associated with an abnormal expansion of adipose tissue and a deregulation of the adipogenesis process [2], which affects the synthesis of adipokines, such as Leptin, Adiponectin, Resistin, Plasminogen activator inhibitor (PAI-1), Monocyte chemoattractant protein 1 (MCP-1), Interleukin-6 (IL-6), and Tumor necrosis factor alpha (TNFα), with autocrine and paracrine functions in inflammation, homeostasis regulation, and adipogenesis, among other processes [3,4]. Experiments in 3T3-L1 preadipocytes and adipose tissue from obese mice showed that ERα regulates insulin sensitivity and glucose tolerance, while ERβ modulates the expression of genes related to adipogenesis by inhibiting the function of the pro-adipogenic marker PPARγ [7]. Works have focused on ERβ-selective ligands that trigger body weight and fat mass reduction, as well as the subexpression of PPARγ without producing secondary effects [10,11]
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