scholarly journals Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models

2016 ◽  
Vol 7 ◽  
Author(s):  
Danmei Su ◽  
Yuanyang Nie ◽  
Airu Zhu ◽  
Zishuo Chen ◽  
Pengfei Wu ◽  
...  
2020 ◽  
Vol 318 (3) ◽  
pp. G542-G553 ◽  
Author(s):  
Yilan Zeng ◽  
Mei Luo ◽  
Liwei Pan ◽  
Yuan Chen ◽  
Siqi Guo ◽  
...  

A lack of sunlight exposure, residence in the northern latitudes, and dietary vitamin D insufficiency are coprevalent with metabolic syndrome (MetS), Type 2 diabetes (T2D), and nonalcoholic fatty liver diseases (NAFLD), implying a potential causality and underlying mechanism. Whether vitamin D supplementation or treatment can improve these disorders is controversial, in part, because of the absence of large-scale trials. Experimental investigations, on the other hand, have uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin that maintained calcium homeostasis. While the large intestine harbors massive numbers of microbes, the small intestine has a minimal quantity of bacteria, indicating the existence of a gating system located in the distal region of the small intestine that may restrain bacterial translocation to the small intestine. Vitamin D receptor (VDR) was found to be highly expressed at the distal region of small intestine, where the vitamin D signaling promotes innate immunity, including the expression of α-defensins by Paneth cells, and maintains the intestinal tight junctions. Thus, a new hypothesis is emerging, indicating that vitamin D deficiency may impair the intestinal innate immunity, including downregulation of Paneth cell defensins, leading to bacterial translocation, endotoxemia, systemic inflammation, insulin resistance, and hepatic steatosis. Here, we review the studies for vitamin D for innate immunity and metabolic homeostasis, and we outline the clinical trials of vitamin D for mitigating MetS, T2D, and NAFLD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Zhang ◽  
Min Feng ◽  
Lisha Pan ◽  
Feng Wang ◽  
Pengfei Wu ◽  
...  

AbstractVertical sleeve gastrectomy (VSG) is one of the most commonly performed clinical bariatric surgeries for the remission of obesity and diabetes. Its effects include weight loss, improved insulin resistance, and the improvement of hepatic steatosis. Epidemiologic studies demonstrated that vitamin D deficiency (VDD) is associated with many diseases, including obesity. To explore the role of vitamin D in metabolic disorders for patients with obesity after VSG. We established a murine model of diet-induced obesity + VDD, and we performed VSGs to investigate VDD's effects on the improvement of metabolic disorders present in post-VSG obese mice. We observed that in HFD mice, the concentration of VitD3 is four fold of HFD + VDD one. In the post-VSG obese mice, VDD attenuated the improvements of hepatic steatosis, insulin resistance, intestinal inflammation and permeability, the maintenance of weight loss, the reduction of fat loss, and the restoration of intestinal flora that were weakened. Our results suggest that in post-VSG obese mice, maintaining a normal level of vitamin D plays an important role in maintaining the improvement of metabolic disorders.


2010 ◽  
Vol 121 (1-2) ◽  
pp. 362-367 ◽  
Author(s):  
Donald Matthews ◽  
Erika LaPorta ◽  
Glendon M. Zinser ◽  
Carmen J. Narvaez ◽  
JoEllen Welsh

Endocrinology ◽  
2021 ◽  
Author(s):  
Tao Tao ◽  
Margaret M Kobleski ◽  
Vaibhav Saini ◽  
Marie B Demay

Abstract Risk factors for non-alcoholic hepatic steatosis include obesity and vitamin D deficiency which commonly co-exist. Thus, the role of vitamin D signaling in the prevention of hepatic steatosis in the absence of obesity or a “western” high fat diet is unclear. These studies were performed to address the role of the adipocyte Vitamin D Receptor (VDR) in the prevention of hepatic steatosis in mice fed a chow diet containing 5% fat by weight. Female mice with adipocyte VDR ablation (Adipoq-Cre; VDR flox/flox) exhibited a mild increase in weight gain at 70 days of age, accompanied by an increase in visceral adipose tissue (VAT) weight. While they did not exhibit evidence of hepatic inflammation or fibrosis, an increase in hepatic lipid content was observed. This was accompanied by an increase in the hepatic expression of genes involved in fatty acid transport and synthesis, as well as fatty acid oxidation. Markers of hepatic inflammation and fibrosis were unaffected by adipocyte VDR ablation. Consistent with the increase in VAT weight in the Adipoq-Cre; VDR flox/flox mice, higher levels of transcripts encoding adiopogenesis related genes were observed in VAT. In contrast to other models of impaired vitamin D signaling studied in the setting of a high fat or “western” diet, the Adipoq-Cre; VDR flox/flox mice do not exhibit hepatic inflammation or fibrosis. These findings suggest that the adipocyte VDR regulates hepatic lipid accumulation, but in the absence of obesity or a high fat diet, is not required to prevent hepatic inflammation or fibrosis.


2019 ◽  
Vol 39 (4) ◽  
pp. 223-237 ◽  
Author(s):  
Muhammad Sajid Hamid Akash ◽  
Fareeha Fiayyaz ◽  
Kanwal Rehman ◽  
Shakila Sabir ◽  
Muhammad Hidayat Rasool

2018 ◽  
Vol 69 (8) ◽  
pp. 2260-2267 ◽  
Author(s):  
Andra Iulia Suceveanu ◽  
Anca Pantea Stoian ◽  
Irinel Parepa ◽  
Claudia Voinea ◽  
Razvan Hainarosie ◽  
...  

Gut microbiota plays a major role in the process of food absorption and low grade inflammation, two key steps in obesity and diabetes mellitus occurrence. Gut microbiota metabolites, such as short chain fatty acids (SCFA), have an important impact over the metabolic pathways like insulin signalling, incretin production and inflammation. [1-3] We aimed to study the microbiota patterns in obese and T2D patients from Black Sea Coast region, considering the ethnic mixture, environmental and geographical particularities, involving diet or various habits in this area. 100 patients and 100 controls matched by age, gender and ethnicity were studied regarding feaces predominance of Lactobacillus and Bifidobacterium species. We compared the results of microbiota patterns from patients to those obtained in a similar control group of healthy subjects. The standard pour plate 0.05% L-cystine enriched method was used to obtain the bacterial cultures and anaerobic conditions. Morphological and biochemical tests were used to identify the Lactobacillus and Bifidobacterium spp. Fecal organic acid concentrations were explored in frozen samples. The association between bacterial counts/organic acid concentrations and independent variables, including age, diet, ethnicity and other risk factors were calculated using multivariable linear regression analysis. Pearson�s correlation coefficients were calculated to detect associations between fecal bacteria counts/organic acid concentrations and laboratory variables (serum biomarkers, body mass index, age, and severity of obesity/T2D according to international scales). Junk and sweet diets, lack of physical activity and familial aggregation of hypercholesterolemia and diabetes were significantly more often present in our T2D/obese patients than in controls. The bacterial counts of the L. acidophilus, L plantarum and L. reuteri subgroups of Lactobacillus sp were significantly lower among patients with T2D and obesity than in controls. The counting of Bifidobacterium spp revealed a higher presence of B. bifidum in controls than in obese or T2D patients. Diet type (junk food and sweets), BMI (]25) and personal history of metabolic disorders were associated with decreased counts of L acidophilus and increased counts of L. fermentum and B. adolescentis in T2D patients. Ethnicity, metabolic disorders history and junk and sweet diet were associated with low counts of L. acidophilus and L. reuteri and low counts of B. longum. Junk and sweet diet was associated with low counts of B. bifidum. Romanian ethnicity and metabolic disorders were associated with low counts of B. choerinum at obese patients, independent of age or previous antidiabetic treatments. The concentrations of acetic and butyric acids were significantly lower in all patients groups, while the concentrations of valeric acid were significantly higher in patients with untreated T2D and obese patients compared to the controls. Low counts of L. acidophilus and L. reuteri were positively correlated with the increased levels of HbA1c, LDL cholesterol, TG and inflammatory markers such as CRP, ESR and IL-6, no matter of diet, age, ethnicity or metabolic disorders history. Also, low counts of B. bifidum and B. infantis were positively correlated with high levels of CRP, IL-6 and TG. In obese patients, statistic analysis results showed that low counts of L. acidophilus, L. plantarum, L. johnsonii and L. reuteri were positively associated with increased levels of CPR, IL-6 and TG, while low counts of B. bifidum, B infantis and B. breve were positively correlated with higher counts of CPR, LDL cholesterol and TG. Low counts of B. bifidum and B choerinum were positively correlated with low counts of HDL cholesterol in Romanian ethnicity patients and in those with previous metabolic disorders. Low bacterial counts of some particular strains of Lactobacillus spp and Bifidobacterium spp were positively correlated with diet type, BMI, Romanian ethnicity and personal history of metabolic disorders obese and T2D patients from Romanian Black Sea Coast Region.


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