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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 …