title: A safflower oil based high-fat/high-sucrose diet modulates the gut microbiota and liver phospholipid profiles associated with early glucose intolerance in the absence of tissue inflammation.
abstract: Omega-6 (n-6) PUFA-rich diets are generally considered obesogenic in rodents. Here, we examined how long-term intake of a high-fat/high-sucrose (HF/HS) diet based on safflower oil affected metabolism, inflammation, and gut microbiota composition.
  
  
  
  We fed male C57BL/6J mice a HF/HS diet based on safflower oil-rich in n-6 PUFAs-or a low-fat/low-sucrose diet for 40 wk. Compared to the low-fat/low-sucrose diet, intake of the safflower-based HF/HS diet only led to moderate weight gain, while glucose intolerance developed at week 5 prior to signs of inflammation, but concurrent with increased levels of linoleic acid and arachidonic acid in hepatic phospholipids. Intake of the HF/HS diet resulted in early changes in the gut microbiota, including an increased abundance of Blautia, while late changes coincided with altered inflammatory profiles and increased fasting plasma insulin. Analysis of immune cells in visceral fat and liver revealed no differences between diets before week 40, where the number of immune cells decreased in the liver of HF/HS-fed mice.
  
  
  
  We suggest that a diet-dependent increase in the n-6 to omega-3 (n-3) PUFA ratio in hepatic phospholipids together with gut microbiota changes contributed to early development of glucose intolerance without signs of inflammation.
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels Banhos
authors.initials: NB
authors.lastname: Danneskiold-Samsøe
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Andersen
authors.affiliation: Rigshospitalet Department 3733, Copenhagen Biocenter, The Bartholin Institute, Copenhagen, Denmark.
authors.forename: Ilinca Daria
authors.initials: ID
authors.lastname: Radulescu
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ann
authors.initials: A
authors.lastname: Normann-Hansen
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Asker
authors.initials: A
authors.lastname: Brejnrod
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Kragh
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Tobias
authors.initials: T
authors.lastname: Madsen
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Nielsen
authors.affiliation: Rigshospitalet Department 3733, Copenhagen Biocenter, The Bartholin Institute, Copenhagen, Denmark.
authors.forename: Knud
authors.initials: K
authors.lastname: Josefsen
authors.affiliation: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense M, Denmark.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fretté
authors.affiliation: National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Even
authors.initials: E
authors.lastname: Fjaere
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.|National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Hellgren
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.|BGI-Shenzhen, Shenzhen, China.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000009:adverse effects*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000097:blood; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology; D018149:Glucose Intolerance / Q000097:blood* / Q000209:etiology; D007249:Inflammation / Q000097:blood / Q000209:etiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012450:Safflower Oil / Q000008:administration & dosage*
chemical_list: D004041:Dietary Fats; D019422:Dietary Sucrose; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D012450:Safflower Oil
keywords: glucose intolerance; hepatic lipid metabolism; inflammation; leucocytes; safflower oil