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| Status |
Public on Feb 02, 2017 |
| Title |
Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
BACKGROUND. Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice.
METHODS. Fourteen lean, healthy individuals randomly received either palm oil (PO) or vehicle (VCL). Hepatic metabolism was analyzed using in vivo 13C/31P/1H and ex vivo 2H magnetic resonance spectroscopy before and during hyperinsulinemic-euglycemic clamps with isotope dilution. Mice underwent identical clamp procedures and hepatic transcriptome analyses.
RESULTS. PO administration decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively. Hepatic triglyceride and ATP content rose by 35% and 16%, respectively. Hepatic gluconeogenesis increased by 70%, and net glycogenolysis declined by 20%. Mouse transcriptomics revealed that PO differentially regulates predicted upstream regulators and pathways, including LPS, members of the TLR and PPAR families, NF-κB, and TNF-related weak inducer of apoptosis (TWEAK).
CONCLUSION. Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD.
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| Overall design |
We performed gene expression microarray analysis of liver derived from mice treated with palm oil under euglycemic hyperinsulinemic clamps and control animals.
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| Contributor(s) |
Álvarez Hernández E, Kahl S, Seelig A, Begovatz P, Irmler M, Kupriyanova Y, Nowotny B, Nowotny P, Herder C, Barosa C, Carvalho F, Rozman J, Neschen S, Jones JG, Beckers J, Hrabe de Angelis M, Roden M |
| Citation(s) |
28112681 |
| Submission date |
Apr 13, 2016 |
| Last update date |
Mar 08, 2018 |
| Contact name |
Johannes Beckers |
| E-mail(s) |
johannes.beckers@helmholtz-munich.de
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| Organization name |
Helmholtz Zentrum Muenchen
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| Department |
Institute of Experimental Genetics
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| Street address |
Ingolstaedter Landstr. 1
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| City |
Neuherberg |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA318412 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE80259_RAW.tar |
129.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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