Interaction of 17β-estradiol and dietary fatty acids on energy and glucose homeostasis in female mice

Nutr Neurosci. 2018 Dec;21(10):715-728. doi: 10.1080/1028415X.2017.1347374. Epub 2017 Jul 7.


Fatty acid-induced hypothalamic inflammation (HI) is a potential cause of the obesity epidemic. It is unclear whether saturated or n-6 polyunsaturated fat is the primary driver of these effects. Premenopausal women are protected, in part, from obesity and associated comorbidities by circulating 17β-estradiol (E2). It is unknown how HI interacts with E2, because most studies of HI do not examine females despite the involvement of E2 in hypothalamic energy homeostasis. Our objective is to determine the effects of high-fat diets with varying levels of linoleic acid (LA) and saturated fat on the energy and glucose homeostasis in female mice with and without E2. Female C57BL/6J mice were fed either a control diet or a 45% kilocalories from fat diet with varying levels of LA (1, 15, or 22.5% kilocalories from LA) with or without E2 (300 μg/kg/day orally). After 8 weeks, the oil-treated high-fat groups gained more weight than control groups regardless of fat type. E2 reduced body fat accumulation in all high-fat groups. Glucose clearance from glucose challenge was impaired by LA. Nighttime O2 consumption was increased by E2, regardless of diet and independent of activity. Neuropeptides and HI genes were not affected by LA or SFA content. These data show that fatty acid type does not affect body weight, but does affect glucose metabolism in females, and these effects are not associated with an induction in HI gene expression.

Keywords: Estrogen; Fatty acids; Inflammation; Linoleic acid; Obesity; Polyunsaturated; Saturated.

MeSH terms

  • Adiposity
  • Animals
  • Blood Glucose / metabolism*
  • Body Composition
  • Body Weight
  • Diet
  • Diet, High-Fat / adverse effects*
  • Dietary Fats / administration & dosage
  • Estradiol / blood
  • Estradiol / pharmacology*
  • Fatty Acids / administration & dosage
  • Female
  • Homeostasis
  • Hypothalamus / metabolism
  • Hypothalamus / physiopathology
  • Interleukin-6 / blood
  • Leptin / blood
  • Linoleic Acid / administration & dosage
  • Mice
  • Mice, Inbred C57BL
  • Obesity / blood
  • Obesity / etiology
  • Obesity / prevention & control
  • Oxygen Consumption
  • Weight Gain


  • Blood Glucose
  • Dietary Fats
  • Fatty Acids
  • Interleukin-6
  • Leptin
  • interleukin-6, mouse
  • Estradiol
  • Linoleic Acid