Estradiol replacement improves high‐fat diet‐induced insulin resistance in ovariectomized rats

Abstract

The role of 17β‐estradiol (E2) in high‐fat diet (HFD)‐induced alteration of the protein kinase B (Akt) signaling pathway in ovariectomized (OVX) rats is unclear. Therefore, we examined whether chronic estrogen replacement restores HFD‐induced impairment in insulin sensitivity by its effects concomitant with alterations in the Akt isoform 2 (Akt2) and Akt substrate of 160 kDa (AS160) phosphorylation in muscles of OVX rats. Nine‐week‐old female Wistar rats underwent ovariectomy under anesthesia; after 4 weeks, subcutaneous implantation of either E2 or placebo (PL) pellets was performed, and HFD feeding was initiated. Intravenous glucose tolerance tests were performed to assess insulin sensitivity. Following insulin injection into rats’ portal vein, the liver and gastrocnemius muscle were dissected for insulin signaling analysis. We observed that HFD increased energy intake and body weight in the PL group; however, it was temporarily decreased in the E2 group. Adipose tissue accumulation was larger in HFD‐fed rats than in normal chow diet (NCD)‐fed rats in the PL group; however, this difference was not observed in the E2 group. HFD reduced insulin sensitivity in the PL group only. In vivo insulin stimulation increased Akt2 phosphorylation in the muscles of NCD‐fed rats in both groups. In contrast, HFD affected insulin‐stimulated phosphorylation of Akt2 and AS160 in the muscles of rats in the PL group but not in the E2 group. Our data suggest that E2 replacement improves HFD‐induced insulin resistance, and this effect is accompanied by the alterations in the Akt2 and AS160 phosphorylation in insulin‐stimulated muscles of OVX rats.

A review of current chemistry, pharmacology, and regulation of endogenous anabolic steroids testosterone, boldenone, and nandrolone in horses

“…Estrogens, antiestrogens, antiepileptic drugs, age, and hyperthyroidism can increase SHBG levels, whereas exogenous androgens, glucocorticoids, growth hormone therapy, hypothyroidism, obesity, and hyperinsulinemia may decrease SHBG (Gerald & Raj, 2022). Testosterone is also the precursor to hormones with potent peripheral activity, namely dihydrotestosterone formed primarily in the skin, liver, and the genitourinary tract by 5α‐reductase, and estradiol formed by Cyp19 with important effects on bone mineralization, epiphyseal plate closure, and insulin sensitivity (Rodd et al, 2004; Simpson et al, 2002; Swerdloff et al, 2017; Yokota‐Nakagi et al, 2022).…”

Insight into genetic, biological, and environmental determinants of sexual-dimorphism in type 2 diabetes and glucose-related traits

“…Estrogen supplementation, another commonly used chemical procedure in rodents, has been shown to restore glucose homoeostasis in ovariectomized female ZDF rats ( 123 ), and improve glucose tolerance and fasting blood glucose levels in males ( 152 ). Estrogen replacement reversed insulin resistance and visceral fat accumulation, and improved insulin sensitivity in the skeletal muscle (when combined with high fat diet) in ovariectomized female Wistar rats ( 153 , 154 ). Estrogen supplementation in ovariectomized female C57BL/6J mice significantly improved blood glucose levels, glucose-stimulated insulin secretion as well as insulin content in pancreatic beta cells ( 155 ) and improved insulin sensitivity in the hepatic tissue ( 156 ).…”

Changes in taste palatability across the estrous cycle are modulated by hypothalamic estradiol signaling

“…Of course, dissecting the ways in which palatability-related behavior changes across estrous phases is a non-trivial problem, because rodents cycle fast—each phase lasts approximately 1 day. One way to deal with this technical difficulty would be to perform tests on ovariectomized rats, such that circulating estradiol levels can be determined by experimenter injection (Taschetto et al, 2018; Yoest et al, 2019; Yokota-Nakagi et al, 2022). We have chosen not to use this technique here, because while it allows nominal control of estradiol levels (in isolation of other sex-specific hormones), it is difficult to be sure that one is administering the hormone of interest at naturalistic concentrations (studies tend to involve estradiol injections in the vicinity of 5µg/0.1mL, versus natural fluctuations between 2-50pg/mL across the cycle; see for instance Yoest et al, 2019).…”