Effects of Sex-Specific Gene on the Adipogenic Differentiation in 3T3-L1 Preadipocytes

Abstract

ObjectivesGlobal statistics indicated that women are more likely to be obese than men, while sex and gender differences have been largely ignored in scientific reports which have caused serious biases in research conclusions. Previously, we have identified female-specific genes including NPR3 (natriuretic peptide receptor 3) in adipose tissue of obese mice by bioinformatics analysis. Here, we further investigated sex-specific effects of the NPR3 gene on the adipogenic differentiation in 3T3-L1 preadipocytes to understand the underlying mechanisms for sex differences. Methods3T3-L1 preadipocytes were treated with/without 1 μM fulvestrant (FUL, estrogen receptor antagonist) and/or 100 nM AP811 (NPR3 antagonist) during the early stage of differentiation. After cell differentiation, triacylglyceride (TG) accumulation was measured by Oil red O staining and mRNA level of markers related with lipid metabolism was determined by qRT-PCR. ResultsKaryotyping revealed two X chromosomes were present in 3T3-L1 cells. After differentiation with FUL and AP811, the NPR3 expression significantly decreased compared with 3T3-L1 cells treated with AP811 alone, indicating that NPR3 might be obesity-induced female-specific gene. Treatment with FUL and AP811 increased TG accumulation, which was accounted for the increased expression of adipogenic markers (PPARγ, CEBPα) and reduced expression of markers involved in mitochondrial biogenesis (NRF1, DRP1). ConclusionsOur data show that the NPR3 gene influences the adipogenic differentiation in a sex-specific manner, suggesting sex- and gender-based strategies for the prevention and treatment of obesity need to be established. Funding SourcesThis work was supported by the Support Program for Women in Science, Engineering and Technology through the Center for Women In Science, Engineering and Technology (WISET) funded by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT).