# A Short S-Equol Exposure Has a Long-Term Inhibitory Effect on Adipogenesis in Mouse 3T3-L1 Cells  
[PERSON]  
1 Laboratorio 2 de Biomedicine Molecular, ENMFH, Instituto Politecnico Nacional,  
Ciudad de Mexico 07320, Mexico; [EMAIL_ADDRESS]  
[PERSON]  
2 Academia de Genomica, CIDIR-Durango, Instituto Politecnico Nacional, Durango 34220, Mexico; [EMAIL_ADDRESS]  
[PERSON]  
3 Laboratorio de Bioquimica Ext structural, ENMFH, Instituto Politecnico Nacional,  
Ciudad de Mexico 07320, Mexico; [EMAIL_ADDRESS]  
[PERSON]  
4 Laboratorio de Farmacologia, Departamento de Ciencias de la Salud, Division de Ciencias Biologicas y de la Salud, Universidad Autonoma Metropolitana-Iztapalapa, Ciudad de Mexico 09340, Mexico; [EMAIL_ADDRESS] (J.C.-A.-P.); [EMAIL_ADDRESS] (A.G.-M.)  
5 Departamento de Farmacobologia, Centro de Investigacion y de Estudios Avanzados del IPN, Sede Sur,
Obesity is mainly exacerbated by the excessive intake of highly caloric food and the lack of physical activity [5], but estrogen reduction is also an important cause of augmented adiposity, mainly in postmenopausal women [6]. Estrogen effects depend on the binding to estrogen receptors (ERs) that act as transcription factors to regulate different processes. Notably, experiments in 3T3-L1 preadipocytes and adipose tissue from obese mice showed that ER\(\alpha\) regulates insulin sensitivity and glucose tolerance, while ER\(\beta\) modulates the expression of genes related to adipogenesis by inhibiting the function of the pro-adipogenic marker PPAR\(\gamma\)[7]. Although estradiol therapy seems to be promising for obesity control, adverse effects usually related to the overexpression of ER\(\alpha\) in female reproductive organs and breasts, and its implication in the induction of proliferation, strongly limit its therapeutic use [8; 9]. Consequently, works have focused on ER\(\beta\)-selective ligands that trigger body weight and fat mass reduction, as well as the subexpression of PPAR\(\gamma\) without producing secondary effects [10; 11]. In the search for new drugs against obesity, plant and food components have attracted increased attention worldwide. Notably, abundant epidemiological evidence suggests that the intake of soy-containing foods has many health benefits [12; 13]. Daidzein is a soy isoflavone that is hydrolyzed by specific gut bacteria to form S-equol, which is a structural homolog of 17-\(\beta\)-estradiol. S-equol has a higher binding affinity to ER\(\beta\) (Ki = 0.73 \(\pm\) 0.2 nmol/L) than ER\(\alpha\) (Ki = 6.41 \(\pm\) 1 nmol/L), which makes it an interesting molecule for obesity control through ER pathway modulation. The presence of a chiral carbon atom at position C-3 of the furan ring allows the formation of a synthetic enantiomer form called R-equol, with a weaker affinity for both ERs [14; 15; 16]. A decade ago, [PERSON] et al. published an interesting report showing that \(\geq\)80% of Asian people are equal producers versus \(\leq\)25% in Western countries (mainly United States and Europe), which is consistent with the highest consumption of soybean and the lowest rate of overweight/obesity in Eastern regions [17]. Congruently, some studies have reported the beneficial effect of equal for the control of overweight and obesity. An epidemiological study conducted on 54 Japanese patients with obesity supplemented with 10 mg of S-equol per day for 12 weeks evidenced reductions in the levels of glycosylated hemoglobin (HbAlc), low-density lipoprotein (LDL-C), vascular Cardio-ankle index (CAVI), and Leptin [18]. On the other hand, treatment of obese diabetic C57 BL/6 mice with 0.05% equal in diet for three weeks induced reductions in serum glucose, cholesterol, and triglyceride levels, as well as in weight gain [19].