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 O 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.

The effects of dietary fatty acids in the physiological outcomes of maternal high-fat diet on offspring energy homeostasis in mice

“…These results are similar to our previous findings of 22.5% producing glucose intolerance in male mice. 17 The results of maternal 22.5% on ITT in females, likewise, were similar to the results of that same diet on adult female mice 35 and to insulin resistance previously demonstrated from dietary LA, 13 through the mechanism of increasing stimulation of the carnitine palmitoyltransferase I system 36 and subsequent inhibition of mitochondrial glucose oxidation. This provides evidence for a relationship between the intergenerational and adult effects on LA on glucose metabolism.…”

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

“…Blood samples were collected after 5-h fasting on day (D) D8 (during STND) and on D23 (9 days on the start of HFD) by tail vein puncture (Analytic Core, MMPC). Plasma E2 on D23 was measured using Mouse/Rat Estradiol ELISA kit (#ES180S, Calbiotech [ 12 , 97 ]. The cytokines Il-6 and TNF-α, the adipokines leptin and resistin, and intestinal hormones, ghrelin and GLP-1 were measured using an ELISA with a Luminex 200 Multiplex system (Millipore, Darmstadt, Germany).…”

“…Ovariectomized rodents provide excellent models for studying estrogen-dependent effects on energy homeostasis. Ovariectomy causes diet-induced obesity, hyperglycemia and insulin resistance in rodents, which can be rescued by estradiol (E2) treatment [ 11 , 12 , 13 , 14 , 15 ]. In further support of a protective role for estrogens, mice lacking estrogen receptors or the estrogen synthesizing enzyme, aromatase, develop obesity [ 16 , 17 , 18 ].…”

Chlorpyrifos Induces Metabolic Disruption by Altering Levels of Reproductive Hormones

“…It has a vital role in preventing excess gain in body weight. Numerous studies have shown that E 2 can reduce blood levels of cholesterol, body-fat accumulation, and increase calcium levels in bone …”