Nonlinear transcriptomic response to dietary fat intake in the small intestine of C57BL/6J mice

Nyima, Tenzin, Müller, Michael, Hooiveld, Guido J. E. J., Morine, Melissa J. and Scotti, Marco (2016) Nonlinear transcriptomic response to dietary fat intake in the small intestine of C57BL/6J mice BMC Genomics, 17 (1). DOI 10.1186/s12864-016-2424-9.

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Text (Diet composition. Main ingredients are in bold (e.g., palm oil is the main source of saturated fats whereas corn starch is the main source of carbohydrates).Table A1.2. Food and caloric intake in week 4. Data refer to the week the mice were killed...)
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Text (Schematic representation of the workflow adopted for the analysis of microarray data. We identified linear and nonlinear response patterns for significantly over-represented GOBP terms. Trends for the response patterns specific to each term were examined )
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[img] Other ( Differentially expressed genes (normalized and processed data) in the three sections of small intestine. There are 1,976 genes in the proximal section, 2,489 genes in the middle part and 313 genes in the distal section. For each gene we indicated ...)
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Text (Count of genes that responded in a significant, dose-dependent way to fat intake (model selection based on AIC). We identified the significant responses in three sections of small intestine (limma library, adjusted p-value < 0.1). Differential gene ...)
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Text (Over-represented Gene Ontology Biological Process (GOBP) terms associated with differentially expressed genes in the three intestinal sections...)
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Text (Over-represented Gene Ontology Biological Process (GOBP) terms that can be found in various intestinal sections. For each GOBP term we specify up- and down-regulated genes (adjusted p-value < 0.1; however, most of the results of gene set enrichment ...)
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Text (Over-represented Gene Ontology Biological Process (GOBP) terms that are completely up-regulated. For each GOBP term we summarize: the total number of genes in the microarray (gene set size, labelled as Set size), the count of genes extracted with our ...)
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Text (Over-represented Gene Ontology Biological Process (GOBP) terms that include up-regulated genes only and can be found in various intestinal sections...)
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Text (Over-represented Gene Ontology Biological Process (GOBP) terms that are completelydown-regulated. Data refer to GOBP terms that can be found in various intestinal sections...)
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Text (Over-represented Gene Ontology Biological Process (GOBP) terms that include down-regulated genes only and can be found in various intestinal sections. For each term we specify the associated differentially expressed genes ...)
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Supplementary data:

Abstract

Background: A high caloric diet, in conjunction with low levels of physical activity, promotes obesity. Many studies are available regarding the relation between dietary saturated fats and the etiology of obesity, but most focus on liver, muscle and white adipose tissue. Furthermore, the majority of transcriptomic studies seek to identify linear effects of an external stimulus on gene expression, although such an assumption does not necessarily hold. Our work assesses the dose-dependent effects of dietary fat intake on differential gene expression in the proximal, middle and distal sections of the small intestine in C57BL/6J mice. Gene expression is analyzed in terms of either linear or nonlinear responses to fat intake.

Results: The highest number of differentially expressed genes was observed in the middle section. In all intestine sections, most of the identified processes exhibited a linear response to increasing fat intake. The relative importance of logarithmic and exponential responses was higher in the proximal and distal sections, respectively. Functional enrichment analysis highlighted a constantly linear regulation of acute-phase response along the whole small intestine, with up-regulation of Serpina1b. The study of gene expression showed that exponential down-regulation of cholesterol transport in the middle section is coupled with logarithmic up-regulation of cholesterol homeostasis. A shift from linear to exponential response was observed in genes involved in the negative regulation of caspase activity, from middle to distal section (e.g., Birc5, up-regulated).

Conclusions: The transcriptomic signature associated with inflammatory processes preserved a linear response in the whole small intestine (e.g., up-regulation of Serpina1b). Processes related to cholesterol homeostasis were particularly active in the middle small intestine and only the highest fat intake down-regulated cholesterol transport and efflux (with a key role played by the down-regulation of ATP binding cassette transporters). Characterization of nonlinear patterns of gene expression triggered by different levels of dietary fat is an absolute novelty in intestinal studies. This approach helps identifying which processes are overloaded (i.e., positive, logarithmic regulation) or arrested (i.e., negative, exponential regulation) in response to excessive fat intake, and can shed light on the relationships linking lipid intake to obesity and its associated molecular disturbances.

Document Type: Article
Additional Information: WOS:000369695500007
Keywords: ABC transporters; Acute-phase response; Cholesterol homeostasis; Cholesterol transport and efflux; Inflammatory response; Small intestine absorption; Transcriptomic response to fat intake
Research affiliation: OceanRep > GEOMAR > FB3 Marine Ecology > FB3-EOE-N Experimental Ecology - Food Webs
Refereed: Yes
DOI etc.: 10.1186/s12864-016-2424-9
ISSN: 1471-2164
Date Deposited: 26 Feb 2016 08:28
Last Modified: 03 May 2017 12:14
URI: http://eprints.uni-kiel.de/id/eprint/31552

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