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

Mol Nutr Food Res. 2017 May;61(5). doi: 10.1002/mnfr.201600528. Epub 2017 Feb 22.


Scope: 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.

Methods and results: 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.

Conclusion: 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.

Keywords: glucose intolerance; hepatic lipid metabolism; inflammation; leucocytes; safflower oil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects*
  • Dietary Fats / administration & dosage
  • Dietary Sucrose / administration & dosage
  • Dietary Sucrose / adverse effects*
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / blood
  • Fatty Acids, Omega-6 / administration & dosage
  • Fatty Acids, Omega-6 / blood
  • Gastrointestinal Microbiome*
  • Gastrointestinal Tract / microbiology
  • Glucose Intolerance / blood*
  • Glucose Intolerance / etiology
  • Inflammation / blood
  • Inflammation / etiology
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Safflower Oil / administration & dosage*


  • Dietary Fats
  • Dietary Sucrose
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Safflower Oil