Weighted Gene Co-Expression Network Analysis Identifies Gender Specific Modules and Hub Genes Related to Metabolism and Inflammation in Response to an Acute Lipid Challenge.

Abstract

Inflammation is characteristic of diet-related diseases including obesity and type 2 diabetes (T2D). However, biomarkers of inflammation that reflect the early stage metabolic derangements are not optimally sensitive. Lipid challenges elicit postprandial inflammatory and metabolic responses. Gender-specific transcriptomic networks of the peripheral blood mononuclear cell (PBMC) were constructed in response to a lipid challenge. Eighty-six adult males and females of comparable age, anthropometric, and biochemical profiles completed an oral lipid tolerance test (OLTT). PBMC transcriptome was profiled following OLTT. Weighted gene coexpression networks were constructed separately for males and females. Functional ontology analysis of network modules was performed and hub genes identified. Two modules of interest were identified in females-an "inflammatory" module and an "energy metabolism" module. NLRP3, which plays a central role in inflammation and STARD3 that is involved in cholesterol metabolism, were identified as hub genes for the respective modules. The OLTT induced some gender-specific correlations of gene coexpression network modules. In females, biological processes relating to energy metabolism and inflammation pathways were evident. This suggests a gender specific link between inflammation and energy metabolism in response to lipids. In contrast, G-protein coupled receptor protein signaling pathway was common to both genders.