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

Estradiol and exercise can decrease risk factors associated with type 2 diabetes (T2D) including total body weight gain and abdominal fat gain. Estradiol functions through estrogen receptor (ER) α and ERß. Some studies suggest that activation of ERα may provide protection against T2D. Female Wistar rats were ovariectomized and fed a high-fat diet for 10 weeks and divided into the following 5 experimental groups: (1) no treatment (control), (2) exercise, (3) estradiol, (4) propylpyrazoletriyl (a selective ERα agonist), and (5) diarylpropionitrile (a selective ERß agonist). ERα activation decreased the abundance of Firmicutes, and ERα and ERß activation increased the abundance of Bacteroidetes. ERα activation decreased food consumption, and ERα and ERß activation increased voluntary activity. Exercise was the only treatment to decrease the blood glucose and serum insulin levels. ERα activation, but not ERß, increased hepatic protein expression of ACC and FAS and decreased hepatic protein expression of LPL. ERα activation also decreased hepatic mRNA expression of PPARα and PPARγ. This study elucidates the functions of estradiol by assessing specific activation of ERα and ERß. As obesity increases the abundance of Firmicutes and decreases the abundance of Bacteroidetes, our study shows that ERα activation can restore the gut microbiome to non-obese abundances. This study further provides novel insights into ERα's role in hepatic fat metabolism via regulation of ACC, FAS, LPL, PPARα, and PPARγ.

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

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. Female Wistar rats were ovariectomized and fed a high-fat diet for 10 wk and divided into the following four experimental groups: 1) no treatment (control), 2) exercise (Ex), 3) estradiol replacement, and 4) Ex + estradiol. 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 noninsulin-stimulated pAkt levels in the WAT. In the liver, estradiol increased the protein expression of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) and estradiol decreased the hepatic protein expression of lipoprotein lipase (LPL). In the WAT, estradiol and exercise increased the protein expression of adipose triglyceride lipase (ATGL). Exercise provides better protection against T2D when considering whole body measurements, which may be due to increased noninsulin-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.NEW & NOTEWORTHY Exercise provides better protection than estradiol against type 2 diabetes when considering whole body measurements including adipose tissue weight, blood glucose levels, and serum insulin levels, which may be due to increased noninsulin-stimulated pAkt in the adipose tissue. However, at the cellular level, several molecular changes in fat metabolism and fat storage occurred in the liver and adipose tissue with estradiol treatment.

Using exam reflections to augment learning.

While teaching, learning, and assessment should undoubtedly encompass more than just focusing on student exam scores, exams are a pervasive assessment tool at many academic institutions. This paper describes a newly developed exam reflection assignment, which is a tool to assist students in successful exam experiences throughout the course. The exam reflection is described and compared and contrasted to other types of exam reflections.

Exercise improves high-fat diet- and ovariectomy-induced insulin resistance in rats with altered hepatic fat regulation.

A high-fat diet (HFD) and loss of endogenous estrogens increases the risk for type 2 diabetes (T2D) and insulin resistance. Although exercise is known to prevent and manage insulin resistance, the cellular mechanisms remain largely unknown, especially in the context of a combined HFD and endogenous estrogen loss via ovariectomy (OVX). This study uses female Wistar rats to assess the effect of diet, endogenous estrogens, an exercise on insulin resistance, serum hormones, hepatic AMPK, hepatic regulators of fat metabolism, and expression of signaling molecules of the brain reward pathway. The combination of the HFD/OVX increased the homeostatic model assessment of insulin resistance (HOMA-IR), the glucose-insulin (G-I) index, and the serum adiponectin and leptin values, and exercise decreased these factors. The combination of the HFD/OVX decreased hepatic pAMPK, and exercise restored hepatic pAMPK, an important regulator of fat and glucose metabolism. Furthermore, consumption of the HFD by rats with intact ovaries (and endogenous estrogens) did not result in these drastic changes compared to intact rats fed a standard diet, suggesting that the presence of estrogens provides whole body benefits. Additionally, the HFD decreased the hepatic protein expression of acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS), two proteins involved in de novo lipid synthesis and increased the hepatic protein expression of lipoprotein lipase (LPL), a protein involved in fat storage. Finally, exercise increased mRNA expression of the dopamine D2 receptor and tyrosine hydroxylase in the dopaminergic neuron cell body region of the ventral tegmental area, which is a key component of the brain reward pathway. Overall, this study demonstrates that exercise prevents insulin resistance even when a HFD is combined with OVX, despite hepatic changes in ACC, FAS, and LPL.

Exercise prevents HFD- and OVX-induced type 2 diabetes risk factors by decreasing fat storage and improving fuel utilization.

Previous studies suggest that the loss of estrogens increase one's risk for type 2 diabetes (T2D), and combining the loss of estrogens with a high-fat diet (HFD) poses an even greater risk for T2D. The extent to which exercise can ameliorate the deleterious effects of estrogen loss combined with a HFD and the molecular mechanisms accounting for the whole body changes is currently unknown. Therefore, we fed female Wistar rats a standard diet or a HFD for 10 weeks. The rats fed the HFD were either ovariectomized (OVX) or their ovaries remained intact. A subset of the HFD/OVX rats also underwent exercise training on a motor-driven treadmill. Exercise significantly reduced the total body weight gain, periuterine white adipose tissue (WAT) weight, hyperglycemia, and hyperinsulinemia. Additionally, the ability to store fat, as measured by lipoprotein lipase (LPL) in the WAT, was increased in the HFD/OVX group; however, exercise reduced the LPL levels. Furthermore, the combination of the HFD with OVX decreased the WAT citrate synthase protein level, which was increased with exercise. These data suggest that even during the combined HFD/OVX physiological state, exercise can decrease several risk factors associated with T2D, decrease fat storage, and increase fuel utilization.

Positive outcomes increase over time with the implementation of a semiflipped teaching model.

The flipped teaching model can engage students in the learning process and improve learning outcomes. The purpose of the present study was to assess the outcomes of a semiflipped teaching model over time. Neurophysiology students spent the majority of class time listening to traditional didactic lectures, but they also listened to 5 online lectures and spent 8-10 class periods completing an active learning assignment. At the end of the term, students completed a survey to assess the outcomes of the active learning assignments. The positive outcomes were greater the second time the course was taught in a semiflipped manner. While completely flipping a course takes a tremendous amount of time, instructors can still obtain positive outcomes by implementing a semiflipped teaching model.