Cellular Mechanism by Which Estradiol Protects Female Ovariectomized Mice From High-Fat Diet-Induced Hepatic and Muscle Insulin Resistance

Abstract

Estrogen replacement therapy reduces the incidence of type 2 diabetes in postmenopausal women; however, the mechanism is unknown. Therefore, the aim of this study was to evaluate the metabolic effects of estrogen replacement therapy in an experimental model of menopause. At 8 weeks of age, female mice were ovariectomized (OVX) or sham (SHAM) operated, and OVX mice were treated with vehicle (OVX) or estradiol (E2) (OVX+E2). After 4 weeks of high-fat diet feeding, OVX mice had increased body weight and fat mass compared with SHAM and OVX+E2 mice. OVX mice displayed reduced whole-body energy expenditure, as well as impaired glucose tolerance and whole-body insulin resistance. Differences in whole-body insulin sensitivity in OVX compared with SHAM mice were accounted for by impaired muscle insulin sensitivity, whereas both hepatic and muscle insulin sensitivity were impaired in OVX compared with OVX+E2 mice. Muscle diacylglycerol (DAG), content in OVX mice was increased relative to SHAM and OVX+E2 mice. In contrast, E2 treatment prevented the increase in hepatic DAG content observed in both SHAM and OVX mice. Increases in tissue DAG content were associated with increased protein kinase Cε activation in liver of SHAM and OVX mice compared with OVX+E2 and protein kinase Cθ activation in skeletal muscle of OVX mice compared with SHAM and OVX+E2. Taken together, these data demonstrate that E2 plays a pivotal role in the regulation of whole-body energy homeostasis, increasing O(2) consumption and energy expenditure in OVX mice, and in turn preventing diet-induced ectopic lipid (DAG) deposition and hepatic and muscle insulin resistance.

High-intensity interval training beneficial effects on body mass, blood pressure, and oxidative stress in diet-induced obesity in ovariectomized mice

“…2 Experimental studies often consider an ovariectomy associated with a HF diet as an attempt to mimic menopause, and the results resemble the metabolic alterations observed in women. 20,21 The decline in the estrogen levels, observed in postmenopausal women and in ovariectomized animals, raises BP. Estrogen regulates the production of NO synthase, liberating the NO that acts as a potent vasodilator to reduce BP.…”

Fıbroblast growth factor 21 and ıts relatıonshıp wıth ınsulın sensıtıvıty ın fırst-degree relatıves of patıents wıth type 2 dıabetes mellıtus

“…Consistently, in our study, plasma FGF 21 concentrations were observed to be positively correlated with HOMA-IR, AUCG, and AUCI and negatively with Matsuda ISI. Camporez et al [20] suggested that FGF 21 protects mice from lipid-induced liver and muscle insulin resistance as one of the possible pathogenetic mechanisms. Furthermore, recently, treatment with FGF 21 has been suggested as a novel therapy for the treatment of insulin resistance and T2DM [21].…”

Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism

“…Hyperinsulinemic-glucose clamps were performed in awake mice as previously described (37). At the end of the clamp, relative flux through PDH (V PDH ) and CS (V CS ) pathways in individual tissues was assessed as the ratio of 13 C 2 acetyl CoA to 13 C 3 alanine (i.e., the precursor and product of PDH flux).…”