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 (PUFAs), specifically linoleic acid (LA), may induce inflammation, gut dysbiosis, and worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or VCD-treated C57BL/6J mice were fed HFD (45% kcal fat) with a high LA:SFA ratio (22.5%: 8%) referred to as 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 23-25 weeks. Compared with VCD-treated mice fed 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 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.