Isocaloric switch from low-fat to Western high-fat diet triggers transcriptomic reprogramming and ectopic olfactory receptor responses

Although Western diet (WD) rich in saturated fat is regarded as a trigger of metabolic disease and inflammation, the role of this diet in the absence of obesity is unclear. We studied the metabolic, inflammatory, anthropometric, and adipose tissue transcriptomic responses of 92 twins to 6 weeks of WD following 6 weeks of a healthy low-fat diet while maintaining stable body weight. The WD increased total, LDL and HDL cholesterol but not triglycerides or free fatty acids and induced transient and moderate increases of insulin resistance and some inflammatory markers after 1 week, which disappeared after 6 weeks. Extensive transcriptomic changes reflected restructuring of subcutaneous abdominal adipose tissue. Olfactory receptor (OR) mRNAs were increased in correlation with insulin resistance, liver, and visceral fat, cytokines like IL-18 and VEGF, but inversely related to adiponectin and extracellular NAMPT. In conclusion, WD triggers metabolic and transcriptomic reprogramming closely linked to ectopic OR responses.