Aerobic training with moderate or high doses of vitamin D improve liver enzymes, LXRα and PGC-1α levels in rats with T2DM.

Dysregulation of key transcription factors involved in hepatic energy metabolism, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and liver X receptor alpha (LXRα), has been observed in T2DM. The present study aims to investigate the effects of aerobic training and vitamin D supplementation on liver enzyme levels and the levels of PGC-1α and LXRα proteins in hepatocytes, in a rat model of T2DM. The study involved 56 male Wistar rats, divided into two groups: one was non-diabetic and acted as a control group (n = 8), and the other had induced diabetes (n = 48). The diabetic rats were then split into six subgroups: two groups received high or moderate doses of vitamin D and aerobic training (D + AT + HD and D + AT + MD); two groups received high or moderate doses of vitamin D alone (D + HD and D + MD); one group underwent aerobic training with vehicle (sesame oil; D + AT + oil), and one group was a diabetic control receiving only sesame oil (oil-receiving). The D + AT + HD and D + HD groups received 10,000 IU of vitamin D, while the D + AT + MD and D + MD groups received 5000 IU of vitamin D once a week by injection. The D + AT + oil group and the sham group received sesame oil. After eight weeks of treatment, body weight, BMI, food intake, serum insulin, glucose, 25-hydroxyvitamin D, ALT, AST, and visceral fat were measured. The levels of PGC-1α and LXRα proteins in the liver was assessed by western blotting. Statistical analysis was performed using the paired t-test, one-way analysis of variance (ANOVA), and the Tukey post hoc test at a significance level of P < 0.05. Body weight, food intake, and BMI decreased significantly in the D + AT + HD, D + AT + MD, D + AT + oil, D + HD, and D + MD groups with the highest reduction being observed in body weight and BMI in the D + AT + HD group. The D + AT + HD group exhibited the lowest levels of insulin, glucose, and HOMA-IR while the D + C group exhibited the highest levels among the diabetic groups. The D + AT + HD and D + AT + MD groups had lower levels of ALT and AST enzymes compared to the other groups with no significant difference between D + AT + HD and D + AT + MD. D + AT + HD (p = 0.001), D + AT + MD (p = 0.001), D + HD (p = 0.023), D + MD (p = 0.029), and D + AT + oil (p = 0.011) upregulated LXRα compared to D + C. Among these groups, D + AT + HD exhibited a more profound upregulation of LXRα than D + AT + MD, D + AT + oil, D + HD, and D + MD (p = 0.005; p = 0.002, p = 0.001, and p = 0.001, respectively). Similarly, D + AT + HD showed a more notable upregulation of PGC-1α compared to D + AT + oil, D + HD, and D + MD (p = 0.002; p = 0.001, and p = 0.001, respectively). Pearson correlation tests showed significant and negative correlations between serum 25-hydroxyvitamin levels and both visceral fat (r = - 0.365; p = 0.005) and HOMA-IR (r = - 0.118; p = 0.009); while positive and significant correlations between the liver-to-bodyweight ratio with both ALT and AST enzymes and also between QUICKI levels with LXRα (r = 0.578; p = 0.001) and PGC-1α (r = 0.628; p = 0.001). Combined administration of aerobic training and vitamin D supplementation potentially improves liver enzymes in type-2 diabetic rats that were simultaneous with upregulating the levels of PGC-1α and LXRα proteins in hepatocytes. These improvements were more significant when combining exercise with high-dose vitamin D supplementation. This study highlights the potential of this combination therapy as a new diabetes treatment strategy.

Vitamin D improves the antidiabetic effectiveness of aerobic training via modulation of Akt, PEPCK, and G6Pase expression.

BACKGROUND: Although the effect of Vitamin D Supplementation (Vit D) on several chronic diseases has been well conceded, its role in diabetes remains ambiguous. The present study investigated the interactive effects of Aerobic Training (AT) and different Vit D doses on Protein Kinase B (Akt), Phosphoenolpyruvate Carboxylase (PEPCK), and Glucose-6-Phosphatase (G6Pase) protein expressions in hepatocytes of type-2 diabetic rats. METHODS: Fifty-six male Wistar rats were divided into 2 groups SHAM (non-diabetic control; n = 8), and diabetic (n = 48). Then, diabetic rats were divided into six groups: AT with high doses of Vit D (D + AT + HD), AT with moderate doses of Vit D (D + AT + MD), high doses of Vit D (D + HD), moderate doses of Vit D (D + MD), AT receiving vehicle (sesame oil; D + AT + oil), and control (oil-receiving). D + AT + HD and D + HD groups received 10,000 IU of Vit D; while D + AT + MD and D + MD groups receive 5000 IU of Vit D once a week by injection; D + AT + oil and SHAM groups received sesame oil. Diabetes was induced via intraperitoneal (IP) injection of streptozotocin (50 mg/kg body weight). After 2 months of intervention, serum insulin, glucose, and visceral fat were measured; protein expressions of Akt, PEPCK, and G6Pase were assessed by western blotting. The paired t-test, one-way analysis of variance (One-Way ANOVA), and the Tukey post hoc test were used at the signification level of P < 0.05. RESULTS: Our data indicate that the diabeticization of rats increased the level of insulin, glucose, and PEPCK and G6Pase protein expressions and decreased the expression of the Akt (P < 0.05 for all variables). Combined AT and moderate or high Vit D significantly reduced body weight (P = 0.001; P = 0.001), body mass index (P = 0.001; P = 0.002), food intake (P = 0.001; P = 0.001) comparing the pre-test with the post-test, respectively. Also, AT and either high or moderate Vit D alone therapies lead to the improvement of the metabolic state, however, their combination had a more significant effect on the treatment of type 2 diabetes. CONCLUSIONS: Findings from the present study suggested that combined Vit D supplementation and AT successfully improve liver function and attenuate insulin resistance via upregulating Akt and downregulating PEPCK and G6Pase expressions, compared with monotherapy.

Alterations of liver enzymes and lipid profile in response to exhaustive eccentric exercise: vitamin D supplementation trial in overweight females with non-alcoholic fatty liver disease.

BACKGROUND: Eccentric exhaustive exercise (EEE) training has been known as a promising training modality to enhance performance and stimulate adaptation in healthy individuals or patients that might also cause abnormal liver enzymes and lipid profiles. Vitamin D (Vit D) supplementation is believed to improve the condition of Non-Alcoholic Fatty Liver Disease (NAFLD) patients. However, there is limited evidence on the effect of Vit D supplementation on the EEE-induced alterations. This study aimed to investigate the effect of short-term supplementation of Vit D on the liver enzymes and lipid profile alterations following EEE in overweight women with NAFLD. METHODS: In this clinical trial, 22 overweight women with NAFLD were randomly divided into experimental and control (n = 11 in each). The experimental group consumed 2000 IU of Vit D per day for six weeks; the control group consumed a lactose placebo daily with the same color, shape, and warmth percentage. Two treadmill EEE sessions were performed before and after the six-week Vit D supplementation. Blood was taken from the antecubital vein to measure the liver enzymes, lipid profile, and Vit D at four stages: Pre 1(before the first EEE session), Post 1(after the first EEE session), Pre 2 (before the second EEE session), and Post 2 (after the second EEE session). RESULTS: The results indicate that Vit D supplementation significantly reduced Bodyweight (BW; P = 0.047), Body Mass Index (BMI; P = 0.044), Body Fat Percentage (BFP; P = 0.001), and Waist Hip Ratio (WHR; P = 0.001) in the experimental group. Additionally, the results showed increased liver enzymes (ALT, AST, and GGT) and lipid profile (TC, TG, and LDL) following EEE. While the HDL levels decreased significantly after EEE. Compared with control, the results of the independent t-test showed significantly lower ALT (P = 0.001; P = 0.001), AST (P = 0.001; P = 0.001), and GGT (P = 0.001; P = 0.001); while significantly higher Vit D (P = 0.001, P = 0.001) in the experimental in both Pre 2 and Post 2; receptively. Also, significantly lower TC (P = 0.001; P = 0.001), TG (P = 0.048; P = 0.001), and LDL (P = 0.001; P = 0.001); while significantly higher HDL (P = 0.001, P = 0.001) were observed in the experimental group compared to the control in both Pre 2 and Post 2; receptively. CONCLUSIONS: Vit D supplementation reduces the liver enzymes and improves lipid profile alterations following EEE in overweight women with NAFLD. Thus, Vit D supplementation can be considered a functional supplement to improve the EEE-induced alteration. TRIAL REGISTRATION: The trial was in the Iranian Clinical Trial Registration Center under the (IRCT20201130049538N1) on 05/07/2021.

Effect of Short-term Vitamin D Supplementation on the Alterations of Glycemic Variables in Response to Exhaustive Eccentric Exercise in Patients with Non-alcoholic Fatty Liver.

BACKGROUND: Exhaustive eccentric exercise (EEE), along with a positive role in weight loss and physiological adaptation, increases liver enzymes and disturbs glucose homeostasis. Many studies have been considered to neutralize the adverse effects of EEE, including vitamin D (Vit D) supplementation. The present study aimed to investigate the effect of short-term Vit D supplementation on the alteration of glycemic variables in response to EEE in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In this clinical trial, 22 overweight women with NAFLD were randomly assigned to control (C; n=11) and experimental (Exp; n=11) groups. C group received a lactose placebo daily with the same color, shape, and warmth percentage; Exp group received 2000 IU of Vit D daily for 6 weeks (42 days). Blood samples were taken to measure the liver enzymes, lipid profile, and Vit D levels alteration at four stages: Pre1(before the first EEE session), post 1 (after the first EEE session), pre 2 (before the second EEE session), and post 2 (after the second EEE session). Repeated measures ANOVA and independent t test were used to analyze the data using SPSS software (version 26) at a significance level of P < 0.05. RESULTS: The results show a significant increase in glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) levels in both C and Exp groups following the EEE (comparing pre 1 and post 1). Also, after 6 weeks of Vit D supplementation, glucose, insulin, and HOMA-IR increased significantly in both C (P = 0.001, P = 0.001, and P = 0.001, respectively) and Exp (P = 0.001, P = 0.001, and P = 0.001, respectively) groups following EEE (comparison of pre 2 and post 2). However, these increases were significantly lower in Exp group compared with the C group (comparing post 2). CONCLUSION: Short-term Vit D supplementation downregulates the increased glucose, insulin, and insulin resistance induced by EEE in patients with NAFLD.