title: Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance.
abstract: 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).
  
  
  CONCLUSIONS
  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.REGISTRATION. ClinicalTrials.gov NCT01736202.
  
  
  BACKGROUND
  Germany: Ministry of Innovation, Science, and Research North Rhine-Westfalia, German Federal Ministry of Health, Federal Ministry of Education and Research, German Center for Diabetes Research, German Research Foundation, and German Diabetes Association. Portugal: Portuguese Foundation for Science and Technology, FEDER - European Regional Development Fund, Portuguese Foundation for Science and Technology, and Rede Nacional de Ressonância Magnética Nuclear.
authors.forename: Elisa Álvarez
authors.initials: EÁ
authors.lastname: Hernández
authors.forename: Sabine
authors.initials: S
authors.lastname: Kahl
authors.forename: Anett
authors.initials: A
authors.lastname: Seelig
authors.forename: Paul
authors.initials: P
authors.lastname: Begovatz
authors.forename: Martin
authors.initials: M
authors.lastname: Irmler
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Kupriyanova
authors.forename: Bettina
authors.initials: B
authors.lastname: Nowotny
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Cristina
authors.initials: C
authors.lastname: Barosa
authors.forename: Filipa
authors.initials: F
authors.lastname: Carvalho
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.forename: Susanne
authors.initials: S
authors.lastname: Neschen
authors.forename: John G
authors.initials: JG
authors.lastname: Jones
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.forename: Martin Hrabě
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000818:Animals; D000074049:Cytokine TWEAK; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000073878:Palm Oil; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D010938:Plant Oils / Q000008:administration & dosage / Q000009:adverse effects*; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D000074049:Cytokine TWEAK; D004041:Dietary Fats; D016328:NF-kappa B; D047492:Peroxisome Proliferator-Activated Receptors; D010938:Plant Oils; C491645:Tnfsf12 protein, mouse; D048069:Tumor Necrosis Factors; D000073878:Palm Oil