Exercise prevents whole body type 2 diabetes risk factors better than estradiol replacement in rats

Abstract

Introduction: The absence of estrogens in postmenopausal women is linked to an increased risk of type 2 diabetes (T2D), and estradiol replacement can decrease this risk. Notably, exercise can also treat and prevent T2D. This study seeks to understand the molecular mechanisms by which estradiol and exercise induce their beneficial effects via assessing whole-body and cellular changes. Methods: Female Wistar rats were ovariectomized and fed a high-fat diet for 10 weeks and divided into the following 4 experimental groups: 1) no treatment (control), 2) exercise (Ex), 3) estradiol replacement, and 4) Ex+estradiol. Results: Both Ex and estradiol decreased the total body weight gain. However, only exercise effectively reduced the white adipose tissue (WAT) weight gain, food intake, blood glucose levels and serum insulin levels. At the molecular level, exercise increased the non-insulin stimulated pAkt levels in the WAT. In the liver, estradiol increased the protein expression of ACC and FAS, and estradiol decreased the hepatic protein expression of LPL. In the WAT, estradiol and exercise increased the protein expression of ATGL. Conclusion: Exercise provides better protection against T2D when considering whole body measurements, which may be due to increased non-insulin stimulated pAkt in the WAT. However, at the cellular level, several molecular changes in fat metabolism and fat storage occurred in the liver and WAT with estradiol treatment.

Estrogen receptor α activation modulates the gut microbiome and type 2 diabetes risk factors

“…Two genes regulated by SREBP‐1c that we measured include FAS and ACC (Griffin & Sul, 2004 ), which are involved in de novo lipid synthesis. Although Ex modulated SREBP‐1c in our study, FAS and ACC protein expression did not change with Ex, which is in accordance with our previous research (Fritsch et al, 2021 ). Additionally, we previously reported that E 2 treatment increases hepatic FAS and ACC protein expression in OVX rats fed a HFD (Fritsch et al, 2021 ).…”

“…Although Ex modulated SREBP‐1c in our study, FAS and ACC protein expression did not change with Ex, which is in accordance with our previous research (Fritsch et al, 2021 ). Additionally, we previously reported that E 2 treatment increases hepatic FAS and ACC protein expression in OVX rats fed a HFD (Fritsch et al, 2021 ). The present study also shows the same increase and further adds to the literature that this increase occurs via ERα activation.…”

“…However, we did show that Ex decreased the glucose and insulin AUC during a glucose tolerance test, which signifies improved glucose control and improved insulin sensitivity. The beneficial effect of Ex decreasing blood glucose and serum insulin levels without improvements due to E 2 has been shown previously (Fritsch et al, 2021). In that study, Ex treatment alone or in combination with E 2 replacement decreased blood glucose and serum insulin in OVX rats fed a HFD, but E 2 treatment alone did not show similar improvements.…”

“…Leptin is secreted from the WAT and simulates feelings of satiety. We and others have previously shown that exercise decreases serum leptin levels (Essig et al, 2000;Fritsch et al, 2021;Jacobs et al, 2020;Metz et al, 2016). The effect of E 2 on serum leptin levels remains unknown.…”

“…We recently published a study showing that exercise prevents whole‐body type 2 diabetes risk factors better than E 2 replacement in OVX rats fed a high‐fat diet, but E 2 altered hepatic proteins involved in lipid metabolism (Fritsch et al, 2021 ). However, the receptors by which E 2 provides benefits remain unknown.…”