Saturated fatty acids and omega-3 polyunsaturated fatty acids improve metabolic parameters in ovariectomized female mice. Effects of dietary fatty acids on metabolic parameters in the state of estrogen deficiency

In menopausal and postmenopausal women, obesity, cardiovascular disease, osteoporosis and gut dysbiosis are induced by loss of ovarian 17β-estradiol (E2). Dietary fatty acid profile high in omega-6 polyunsaturated fatty acids (PUFAs), specifically linoleic acid (LA), and low in coconut oil saturated fatty acids (SFAs) and omega-3 PUFAs may worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or estradiol benzoate (EB)-treated ovariectomized C57BL/6J and transgenic fat-1 mice were fed high-fat diet (HFD, 45% kcal fat) with a high LA:SFA ratio (22.5%:8%; 22.5% LA diet) or a HFD with a low LA:SFA ratio (1%:31%; 1% LA) diet for a period of 14-15 weeks. EB treatment rescued obesity, glucose intolerance, and bone loss in OVX mice. fat-1 mice fed 1% LA diet mitigated weight gain and adiposity in Veh-treated OVX mice. fat-1 mice fed 22.5% LA diet had increased EE and activity as wheel running in EB-treated OVX mice. Except EB treatment, coconut oil SFAs and omega-3 FAs can protect against glucose intolerance. Apparent improvement of insulin sensitivity was achieved by EB treatment in both WT and fat-1 mice fed 1% LA diet, while fat-1 mice fed 22.5% LA diet was protected against insulin resistance without EB treatment. Increase of relative abundance of gut microbial taxa as SCFA producers were associated with omega-3 FAs production and improved energy homeostasis. These data suggest that a balanced dietary FA profile containing coconut oil SFAs, and a lower ratio of omega-6/omega-3 FAs is a safer strategy for alleviating metabolic disorders during E2 deficiency.