Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance

作者：Hernandez Elisa Alvarez; Kahl Sabine; Seelig Anett; Begovatz Paul; Irmler Martin; Kupriyanova Yuliya; Nowotny Bettina; Nowotny Peter; Herder Christian; Barosa Cristina; Carvalho Filipa; Rozman Jan; Neschen Susanne; Jones John G; Beckers Johannes; de Angelis Martin Hrabe; Roden Michael

来源：Journal of Clinical Investigation, 2017, 127(2): 695-708.

DOI：10.1172/JCI89444

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 C-13/P-31/H-1 and ex vivo H-2 magnetic resonance spectroscopy before and during hyperinsulinemiceuglycemic 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-kB, 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.

• 出版日期2017-2-1