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

Abstract

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
• Obesity
• Inflammation
• Saturated
• Polyunsaturated
• Linoleic acid

Acknowledgements

The authors thank Dr Sara Campbell for the use of the EMD Millipore MAGPIX^® Multiplex^® System and Dr Judith Storch for the use of the Comprehensive Lab Animal Monitoring System and EchoMRI Body Composition Analyzer.

Disclaimer statements

Contributors KJM and TAR contributed to conceptualization; KJM, AY, and TAR contributed to methodology; KJM, MRH, NM, and TAR contributed to formal analysis; KJM, MRH, NM, AY and TAR contributed to investigation; KJM, MRH, and TAR contributed to writing, review, and editing; TAR contributed to funding acquisition and supervised the research.

Funding This research was supported by funds from USDA-NIFA NJ06107 and from National Institutes of Health R00DK083457, R00DK083457-S1, and P30ES005022.

Conflicts of interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethics approval None.

ORCID

Kyle J. Mamounis http://orcid.org/0000-0002-5489-0198

Ali Yasrebi http://orcid.org/0000-0003-1745-4298

Troy A. Roepke http://orcid.org/0000-0001-5426-2266