Saturated Fatty Acids and Omega-3 Polyunsaturated Fatty Acids Improve Metabolic Parameters in Ovariectomized Female Mice.

In menopausal and postmenopausal women, the risk for obesity, cardiovascular disease, osteoporosis, and gut dysbiosis are elevated by the depletion of 17ß-estradiol. A diet that is high in omega-6 polyunsaturated fatty acids (PUFAs), particularly linoleic acid (LA), and low in saturated fatty acids (SFAs) found in coconut oil and omega-3 PUFAs may worsen symptoms of estrogen deficiency. To investigate this hypothesis, ovariectomized C57BL/6J and transgenic fat-1 mice, which lower endogenous omega-6 polyunsaturated fatty acids, were treated with either a vehicle or estradiol benzoate (EB) and fed a high-fat diet with a high or low PUFA:SFA ratio for ~15 weeks. EB treatment reversed obesity, glucose intolerance, and bone loss in ovariectomized mice. fat-1 mice fed a 1% LA diet experienced reduced weight gain and adiposity, while those fed a 22.5% LA diet exhibited increased energy expenditure and activity in EB-treated ovariectomized mice. Coconut oil SFAs and omega-3 FAs helped protect against glucose intolerance without EB treatment. Improved insulin sensitivity was observed in wild-type and fat-1 mice fed 1% LA diet with EB treatment, while fat-1 mice fed 22.5% LA diet was protected against insulin resistance without EB treatment. The production of short-chain fatty acids by gut microbial microbiota was linked to omega-3 FAs production and improved energy homeostasis. These findings suggest that a balanced dietary fatty acid profile containing SFAs and a lower ratio of omega-6:omega-3 FAs is more effective in alleviating metabolic disorders during E2 deficiency.

Coconut Oil Saturated Fatty Acids Improved Energy Homeostasis but not Blood Pressure or Cognition in VCD-Treated Female Mice.

Obesity, cardiometabolic disease, cognitive decline, and osteoporosis are symptoms of postmenopause, which can be modeled using 4-vinylcyclohexene diepoxide (VCD)-treated mice to induce ovarian failure and estrogen deficiency combined with high-fat diet (HFD) feeding. The trend of replacing saturated fatty acids (SFAs), for example coconut oil, with seed oils that are high in polyunsaturated fatty acids, specifically linoleic acid (LA), may induce inflammation and gut dysbiosis, and worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or VCD-treated C57BL/6J mice were fed a HFD (45% kcal fat) with a high LA:SFA ratio (22.5%: 8%), referred to as the 22.5% LA diet, or a HFD with a low LA:SFA ratio (1%: 31%), referred to as 1% LA diet, for a period of 23 to 25 weeks. Compared with VCD-treated mice fed the 22.5% LA diet, VCD-treated mice fed the 1% LA diet showed lower weight gain and improved glucose tolerance. However, VCD-treated mice fed the 1% LA diet had higher blood pressure and showed evidence of spatial cognitive impairment. Mice fed the 1% LA or 22.5% LA diets showed gut microbial taxa changes that have been associated with a mix of both beneficial and unfavorable cognitive and metabolic phenotypes. Overall, these data suggest that consuming different types of dietary fat from a variety of sources, without overemphasis on any particular type, is the optimal approach for promoting metabolic health regardless of estrogen status.