Vitamin D prevents hepatic steatosis and cardiovascular damage in a rat model of fatty Western diet

The glycerol phosphate pathway produces more than 90% of the liver triacylglycerol (TAG). LysoPA, an intermediate in this pathway, is produced by glycerol-3-phosphate acyltransferase. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), whose gene was recently cloned, contains lysophospholipase D activity, which produces LysoPA from lysophospholipids. Whether human GDPD3 plays a role in hepatic TAG homeostasis is unknown. We hypothesized that human GDPD3 increases LysoPA production and availability in the glycerol phosphate pathway, promoting TAG biosynthesis. To test our hypothesis, we infected C57BL/6J mice with adeno-associated virus encoding a hepatocyte-specific albumin promoter that drives GFP (control) or FLAG-tagged human GDPD3 overexpression and fed the mice chow or a Western diet to induce hepatosteatosis. Hepatic human GDPD3 overexpression induced LysoPA production and increased FA uptake and incorporation into TAG in mouse hepatocytes and livers, ultimately exacerbating Western diet-induced liver steatosis. Our results also showed that individuals with hepatic steatosis have increased GDPD3 mRNA levels compared with individuals without steatosis. Collectively, these findings indicate that upregulation of GDPD3 expression may play a key role in hepatic TAG accumulation and may represent a molecular target for managing hepatic steatosis.

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Vitamin D and hydroxychloroquine reduce renal injury and Ki67 expression in a rat model of IgA nephropathy via TLR4

Chinese Medical Journal ◽

10.1097/cm9.0000000000001618 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

You Li ◽

Wei Li ◽

Hong Jiang

Keyword(s):

Vitamin D ◽

Iga Nephropathy ◽

Rat Model ◽

Renal Injury ◽

Ki67 Expression

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A Combination Treatment of Raloxifene and Vitamin D Enhances Bone-to-Tendon Healing of the Rotator Cuff in a Rat Model

The American Journal of Sports Medicine ◽

10.1177/0363546520927015 ◽

2020 ◽

Vol 48 (9) ◽

pp. 2161-2169

Author(s):

Dong Min Kim ◽

In Kyoung Shim ◽

Myung Jin Shin ◽

Jae Hee Choi ◽

Yu Na Lee ◽

...

Keyword(s):

Vitamin D ◽

Rotator Cuff ◽

Bone Healing ◽

Rat Model ◽

Combination Treatment ◽

Biomechanical Testing ◽

Female Rats ◽

Muscle Quality ◽

Control Group ◽

The Mean

Background: Tearing and degeneration of the rotator cuff at the tendon-to-bone junction are common in adults aged ≥50 years. Few studies have reported on the relationship between estrogen and the rotator cuff enthesis. In addition to preventing bone loss, selective estrogen receptor modulators have been shown to improve tendon and muscle quality. Purpose: To evaluate the effects of raloxifene (RLX) and vitamin D on rotator cuff tendon-to-bone healing in a rat model. Study Design: Controlled laboratory study. Methods: A total of 29 female rats (58 shoulders) were assigned to 4 groups: (1) control group, (2) ovariectomy (OVX)–only group, (3) no RLX group (OVX and rotator cuff repair [RCR]), and (4) RLX group (OVX, RCR, and RLX). Rats that did not undergo rotator cuff tear (RCT) surgery were divided into the control and OVX-only groups according to OVX surgery. Rats that underwent RCT surgery and RCR were divided into the no RLX and RLX groups according to RLX and vitamin D administration. An estrogen-deficient state was induced by OVX at 12 weeks of age. Bone mineral density (BMD) and trabecular bone characteristics were measured by micro–computed tomography, and healing of the tendon-to-bone junction was evaluated by biomechanical testing, histomorphometry, and micro–magnetic resonance imaging (MRI). Results: The mean final body weight (BW; 461.6 ± 47.3 g) of the OVX-only group was significantly higher and BMD (0.25 ± 0.07 g/cm3) was significantly lower ( P < .001) than the mean final BW (338.5 ± 35.1 g) and BMD (0.48 ± 0.05 g/cm3) of the control group. In contrast, the RLX group showed that the BW (369.6 ± 35.8 g) and BMD (0.41 ± 0.08 g/cm3) were not significantly different from the control group. The RLX group had a significantly higher histomorphometric total score (8.50 ± 1.05) than the no RLX group (4.83 ± 2.48). On biomechanical testing, the RLX group (29.7 ± 9.1 N) showed a significantly higher load to failure than the no RLX group (19.4 ± 8.8 N). On micro-MRI, the RLX group had a more homogeneous low signal and tendon continuity than the no RLX group. Conclusion: The combination treatment of RLX and vitamin D prevented a decrease in local BMD (greater tuberosity of the proximal humerus) and enhanced tendon-to-bone healing of the rotator cuff in a rat model. Clinical Relevance: This study induced an estrogen-deficient state similar to the human postmenopausal state and used drugs that are actually being prescribed in a clinical situation.

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Vitamin D Promotes Adiposity But Improves Associated Metabolic Derangements In An Obese Rat Model

QJM ◽

10.1093/qjmed/hcaa065 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

N A Mohamed ◽

A A Seif ◽

M S Abdelhamid ◽

R S A Eissa

Keyword(s):

Body Mass Index ◽

Vitamin D ◽

Adipose Tissue ◽

Lipid Profile ◽

Body Mass ◽

Visceral Adipose Tissue ◽

Rat Model ◽

Dose Group ◽

Tnf Α ◽

Visceral Adipose

Abstract Background Obesity is a worldwide problem and is a major risk factor for chronic diseases. The relation between obesity and vitamin D is not completely understood. Obesity is associated with vitamin D insufficiency. Some studies claim that vitamin D may reduce lipogenesis and others claim that vitamin D can promote adipogenesis. Aim of the study This study was planned to evaluate the effect of alteration in vitamin D level on body weight and adipose tissue metabolism in an obese rat model. Methods 32 Female Albino-rats were randomly allocated into: control group (C, n = 8), fed on control diet containing 1000 IU vitamin D/kg diet, and a high caloric diet group (HCD, n = 32). The HCD group was further subdivided into 3 groups according to the vitamin D dose into: standard vitamin D dose group (HCD+SVD) containing 1000 IU vitamin D/kg diet, low vitamin D dose group (HCD+LVD) containing 25 IU vitamin D/kg diet and high vitamin D dose group (HCD+HVD) containing 5169 IU vitamin D/kg diet. Body mass index, serum vitamin D, glucose, lipid profile, TNF-α and adipose tissue UCP-1 were measured. Different fat depots were weighed and histopathologically assessed. Results HCD+HVD group showed a significant increase in the final body mass index and in the different fat depot weights compared to all groups. Compared to the HCD+SVD group, the HCD+HVD group showed significantly lower serum total cholesterol and LDL-c levels, while it showed a non-significant change in serum glucose, TNF-α and visceral adipose tissue UCP-1. A significant negative correlation was found between serum 25(OH)D and visceral adipose tissue UCP-1. HCD+LVD showed the highest visceral adipose tissue UCP-1 compared to all groups. Conclusion Vitamin D promoted adiposity and decreased visceral adipose tissue UCP-1 but improved the associated derangements in lipid profile.

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