Estradiol Prevents Fat Accumulation and Overcomes Leptin Resistance in Female High-Fat Diet Mice

Abstract

In premenopausal and menopausal women in particular, suboptimal estrogens have been linked to the development of the metabolic syndrome as major contributors to fat accumulation. At the same time, estrogens have been described to have a role in regulating body metabolic status. We evaluated how endogenous or administered estrogens impact on the changes associated with high-fat diet (HFD) consumption in 2 different paradigms; ovarian-intact and in ovariectomized mice. When estradiol (E2) was cyclically administered to ovarian-intact HFD-fed mice for 12 weeks, animals gained significantly less weight than ovarian-intact vehicle controls (P < .01). This difference was mainly due to a reduced caloric intake but not to an increase in energy expenditure or locomotor activity. This E2 treatment regime to mice exposed to HFD was overall able to avoid the increase of visceral fat content to levels of those found in mice fed a regular chow diet. In the ovariectomized model, the main body weight and fat content reducing action of E2 was not only through decreasing food intake but also by increasing the whole-body energy expenditure, locomotor activity, and by inducing fat oxidation. Importantly, these animals became responsive to the anorexigenic effects of leptin in contrast to the vehicle-treated and the pair-fed control groups (P < .01). Further, in vitro hypothalamic secretion experiments revealed that treatment of obese mice with E2 is able to modulate the secretion of appetite-regulating neuropeptides; namely, E2 increased the secretion of the anorectic neuropeptide α-melanocyte-stimulating hormone and decreased the secretion of the orexigenic neuropetides neuropeptide Y and Agouti-related peptide. In conclusion, differences in response to E2 treatment of HFD-fed animals depend on their endogenous estrogenic status. Overall, E2 administration overcomes arcuate leptin resistance and partially prevents fat accumulation on these mice.

Low-Dose Mineralocorticoid Receptor Blockade Prevents Western Diet–Induced Arterial Stiffening in Female Mice

“…In contrast to our study, others have reported resistance to the metabolic and CV complications associated with high fat diets in female mice, 38 suggesting estrogen-mediated CV protection. 39 Such studies have mostly utilized high fat diets rather than diets high in both fat and refined sugars like the diet used in this investigation.…”

Changes in body composition and mRNA expression of ghrelin and lipoprotein lipase in rats treated with leuprolide acetate, a GnRH agonist

“…It has been reported that decreasing E 2 causes not only an overproduction of NPY, but also an impaired leptin sensitivity in ovariectomized rats (31). Estrogen replacement has been studied as a method to prevent increases in body weight in experimental and clinical trials (32,33). However, in the present study, the OVX+LA group exhibited less FM and FFM compared with that in the OVX group.…”

Obesogen effects after perinatal exposure of 4,4′-sulfonyldiphenol (Bisphenol S) in C57BL/6 mice

“…Estrogen and androgen promote energy homeostasis, reduce fat body mass and ameliorate insulin resistance (ie enhance insulin sensitivity) (Mauvais-Jarvis et al, 2013;Navarro et al, 2015). However, suboptimal or deficient levels of estrogens have been linked to the fat accumulation and obesity in female (Litwak et al, 2014). Likewise, low testosterone levels are strongly correlated with obesity in men (Navarro et al, 2015).…”