A High‐Fat Diet Activates Inflammatory Signaling in Human Skeletal Muscle Cultures from Severely Obese Women

Abstract

The incidence of metabolic disease and severe obesity continues to rise; likely associated with consumption of a Western, high-fat diet. Several mechanisms have been postulated to account for comorbidities associated with severe obesity; one being inflammation. The objective of this study was to determine whether metabolic and/or inflammatory gene networks were differentially regulated in human skeletal muscle cell cultures (HSkMC) from lean and severely obese women as a response to lipid oversupply. RNA in HSkMC from lean and severely obese women were isolated after a 48hr lipid incubation (250µM oleate:palmitate), designed to imitate a high-fat diet. Genome-wide expression data was acquired using Illumina HumanHT-12 v4.0 Expression BeadChip. Network and pathway analysis was done using MetaCore software. The number of inflammatory response pathways associated with genes differentially regulated by the lipid treatment was 66, including the top responses, HMGB1/RAGE, TNF-R2, TSLP, and IL-17 signaling pathways, all of which are associated with pro-inflammatory cytokine production. In conclusion, the activation of inflammatory signaling due to the up-regulation of cytokine regulators in response to a high fat diet in the severely obese could be the link between obesity and metabolic dysfunction.