Modulation of Murine Intestinal Gene Expression by Dietary Fat: Spatial Variation and Saturation Effect

Thesis summary: Traditional approaches investigate the linear effect of high-fat over-consumption on transcriptomic data. However, many biological processes occur in a nonlinear fashion. The objective of this PhD thesis is to study the response types of dietary fat mediated differentially expressed genes (i.e., linear response; nonlinear response: logarithmic, exponential, quadratic and cubic) along the longitudinal axis of the small intestine. The main goal is to assess the presence of: (1) gene-specific response type, which refers to genes that preserve the same response pattern in the whole small intestine; (2) section-specific response type, which explains how particular genes behave in different ways according to the intestinal section where they are expressed. This thesis presents two genome-wide transcriptome analyses that quantified the effects of two dietary lipid interventions in different sections of the small intestine of C57BL/6J mice. The first study includes the analysis of transcriptomic data collected from three sections of the small intestine (i.e., proximal, middle and distal). Data were collected after four weeks of dietary intervention during which mice were fed with various levels of fat (i.e., fat providing 10%, 20%, 30% or 45% kcal out of the total energy intake). Different intestinal sections were expected to exhibit regionalized functionality and display unique digestive and absorptive capacity. The goal was investigating linear and nonlinear (i.e., logarithmic, exponential, quadratic or cubic) transcriptomic responses as a continuous function of dietary fat intake along the longitudinal axis of small intestine. Middle section was the most responsive to dietary fat, and the majority of the genes showed linear response to fat intake. The highest relative importance of logarithmic (saturated) and exponential (unsaturated) response was in the proximal and in the distal section, respectively. Such pattern is coherent with the progressive absorp