Estrogen deprivation aggravates cardiac hypertrophy in nonobese Type 2 diabetic Goto–Kakizaki (GK) rats

Abstract

Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto–Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) (n = 6/subgroup). Four months after the operation, the rats were killed, and the heart was excised rapidly. Metabolic parameters, cardiomyocytes hypertrophy, cardiac fibrosis, and biochemical parameters were determined. GK rats had hyperglycemia with hypoinsulinemia, and estrogen deprivation did not increase the severity of T2DM. Cardiac hypertrophy, cardiac oxidative stress, and phosphor-antinuclear factor κB were higher in WTO and GKS rats than WTS rats, and they markedly increased in GKO rats compared with GKS rats. Furthermore, cardiac fibrosis, transforming growth factor-β, Bax, phosphor-p38, and peroxisome proliferator- activated receptor γ coactivator-1α expression were increased in GKS and GKO rats compared with the lean rats. However, mitochondrial dynamics proteins including dynamin-related protein 1 and mitofusin-2 were not altered by T2DM and estrogen deprivation. Although estrogen deprivation did not aggravate T2DM in GK rats, it increased the severity of cardiac hypertrophy by provoking cardiac inflammation and oxidative stress in nonobese GK rats.

Anomalous bone changes in ovariectomized type 2 diabetic rats: inappropriately low bone turnover with bone loss in an estrogen-deficient condition

“…As expected, these rats exhibited a marked decrease in uterine weight at 4 mo post-OVX, i.e., 0.56 Ϯ 0.20 g Sham-WT vs. 0.14 Ϯ 0.02 g OVX-WT (P Ͻ 0.05; n ϭ 10/group) and 0.58 Ϯ 0.05 g Sham-GK vs. 0.18 Ϯ 0.02 g OVX-GK (P Ͻ 0.05; n ϭ 10/group). This change in the reproductive system was consistent with the deterioration of ovarian function associated with OVX and thus inducing estrogen deficiency in these rats, as reported previously (3). Having established the OVX models, we then focused on the changes in calcium and bone metabolism.…”

“…At 9 mo old, WT and GK rats were subdivided into sham-operated (Sham-WT; n ϭ 10, Sham-GK; n ϭ 10) and ovariectomized groups (OVX-WT; n ϭ 10, OVX-GK; n ϭ 10). The circulating levels of estradiol in Sham-WT, Sham-GK, OVX-WT, and OVX-GK have been reported to be 48.6 Ϯ 9.2, 49.6 Ϯ 3.7, 26.6 Ϯ 2.6, and 30.1 Ϯ 2.1 pg/mL, respectively (3). Four months after surgery (at 13 mo old), the animals were subcutaneously injected with two separate doses of calcein (10 mg/kg body wt) on day 7 and 1 before euthanasia.…”

“…As previously described by Aeimlapa et al (1), tibiae were enwrapped and scanned with moist gauze at 65 kV, 615 A [Skyscan 1178 high-speed in vivo/ex vivo microcomputed tomography (CT); Bruker MicroCT, Kontich, Belgium]. Cortical BMD (g/cm 3 ) was analyzed at 14.110 -18.360 mm distal to the proximal growth plate (tibial midshaft). The results are expressed as percentage of Sham-WT.…”

Progesterone eliminates 17β-estradiol-Mediated cardioprotection against diabetic cardiovascular dysfunction in ovariectomized rats

“…Given that there was no significant difference between the combined and the E2+Veh groups, it can also be concluded that P4 in combination with E2 eliminates the beneficial effects of E2 on insulin resistance. Evidence suggests that reduction of E2 along with T2D causes an increase in dysfunction of beta-pancreatic cells [ 29 ], and in humans similar to rodents, the loss of E2 results in metabolic imbalances [ 30 ]. P4 has been shown to cause insulin resistance [ 31 ] and reduce insulin sensitivity in gestational diabetes by reducing the expression of glucose transporter 4 (GLUT4) in muscle and fat tissues [ 32 ].…”

Effects of Supraphysiological Doses of Anabolic Androgenic Steroids on the Left Ventricles of Male and Female Mice Submitted to Swimming

“…This hormone is a protective factor for the cardiovascular system, and such concept has already been evidenced in some previously published papers. [21][22][23] Nonetheless, some authors suggested that the decrease in the diameter of the left ventricle in female animals under supraphysiological doses of the AAS could be due to an increase in the left ventricular wall, leading to a decrease in the ventricular chamber volume with consequent hypertension, resulting in heart failure and left ventricular hypertrophy. 24,25 Another hypothesis that would lead to an increase of muscle mass in females would be based on the same reason observed by Hayward et al, 26 who administered AAS to women and consequently observed an increase in cardiac muscle mass.…”