Effect of vitamin D supplementation on inflammation and nuclear factor kappa-B activity in overweight/obese adults: a randomized placebo-controlled trial

Mousa, Aya; Naderpoor, Negar; Johnson, Josphin; Sourris, Karly C.; Courten, Maximilian Pangratius J De; Wilson, Kirsty; Scragg, Robert; Plebanski, Magdalena

doi:10.1038/s41598-017-15264-1

Cited by 41 publications

(32 citation statements)

References 58 publications

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“…The plasma levels of several inflammatory markers, including IL1β, IL6, IL8, IL10, IL12, IL17, IL18, IL23, IL33, interferon alpha (INFα), and gamma (INFγ), monocyte chemoattractant protein‐1 (MCP‐1), and tumor necrosis factor (TNF), were measured simultaneously in a single sample (25 μL) using a commercial bead‐based multi‐analyte assay (LEGENDplex, Biolegend, CA, USA) as previously described. [ 47 ] Briefly, a kit‐specific protocol on 96‐well plates was performed following manufacturer's instructions. After addition of beads, samples, standards and reagents, plates were incubated in the dark for 2 h at 600 rpm.…”

Section: Methodsmentioning

confidence: 99%

Low AMY1 Copy Number Is Cross‐Sectionally Associated to an Inflammation‐Related Lipidomics Signature in Overweight and Obese Individuals

Mayneris‐Perxachs

Mousa

Naderpoor

et al. 2020

Molecular Nutrition Food Res

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Scope Reduced amylase 1 (AMY1) copy numbers are associated with obesity, insulin resistance, and inflammation. Although mechanisms linking AMY1 copy number with metabolic disorders are poorly understood, recent findings suggest that lipids play a key role. Methods and results Plasma lipidomic signatures associated with AMY1 copy number are explored in 57 non‐diabetic overweight/obese subjects aged 18–60. Serum amylase and inflammatory cytokines levels are also measured. AMY1 copy number is strongly associated with the serum amylase concentration. Participants are divided into low‐(≤4) and high‐(>4) AMY1 carriers based on the median. Low‐AMY1 carriers have higher BMI and fat mass. They also have higher levels of dihexosylceramides (R = −0.27, p = 0.044), cholesterol esters (CE) (R = −0.32, p = 0.020), alkylphosphatidylcholines [PC(O)] (R = −0.33, p = 0.014), and sphingomyelins (SM) (R = −0.38, p = 0.005). From 459 lipid species, 28 differ between low‐ and high‐AMY1 carriers. These include CE species with long‐chain PUFA; PC(O) and PC plasmalogens containing arachidonic acid; and PC, mono‐, di‐, and tri‐hexosylceramides, and SM containing saturated fatty acids (mainly C16:0 and C20:0). This lipidomic signature is strongly associated with inflammatory cytokines, which are also negatively associated with the AMY1 copy number. Conclusion A lipidomics signature associated with low AMY1 copy numbers is revealed, which is linked to obesity and chronic low‐grade inflammation.

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Section: Methodsmentioning

confidence: 99%

Low AMY1 Copy Number Is Cross‐Sectionally Associated to an Inflammation‐Related Lipidomics Signature in Overweight and Obese Individuals

Mayneris‐Perxachs

Mousa

Naderpoor

et al. 2020

Molecular Nutrition Food Res

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“…Pharmacological activation of VDR signaling by a synthetic ligand in combination with a Bromodomain‐containing protein 9, or BRD9 inhibitor is able to partially restore β‐cell function and glucose homeostasis in T2DM mouse models . In line with this, vitamin D supplementation has been reported to improve chronic low‐grade inflammation and diabetic condition in patients with type T2DM . Therefore, targeting VDR signaling highlights great potential for ameliorating chronic metabolic diseases.…”

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confidence: 85%

Vitamin D Receptor Activation in Liver Macrophages Ameliorates Hepatic Inflammation, Steatosis, and Insulin Resistance in Mice

et al. 2020

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Background and Aims Obesity‐induced chronic inflammation is a key component in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and insulin resistance. Increased secretion of proinflammatory cytokines by macrophages in metabolic tissues promotes disease progression. In the diet‐induced obesity (DIO) mouse model, activation of liver resident macrophages, or Kupffer cells (KCs), drives inflammatory responses, which recruits circulating macrophages and promotes fatty liver development, and ultimately contributes to impaired hepatic insulin sensitivity. Hepatic macrophages express the highest level of vitamin D receptors (VDRs) among nonparenchymal cells, whereas VDR expression is very low in hepatocytes. VDR activation exerts anti‐inflammatory effects in immune cells. Approach and Results Here we found that VDR activation exhibits strong anti‐inflammatory effects in mouse hepatic macrophages, including those isolated from DIO livers, and mice with genetic loss of Vdr developed spontaneous hepatic inflammation at 6 months of age. Under the chronic inflammation conditions of the DIO model, VDR activation by the vitamin D analog calcipotriol reduced liver inflammation and hepatic steatosis, significantly improving insulin sensitivity. The hyperinsulinemic euglycemic clamp revealed that VDR activation greatly increased the glucose infusion rate, while hepatic glucose production was remarkably decreased. Glucose uptake in muscle and adipose did not show similar effects, suggesting that improved hepatic insulin sensitivity is the primary contributor to the beneficial effects of VDR activation. Finally, specifically ablating liver macrophages by treatment with clodronate liposomes largely abolished the beneficial metabolic effects of calcipotriol, confirming that VDR activation in liver macrophages is required for the antidiabetic effect. Conclusions Activation of liver macrophage VDRs by vitamin D ligands ameliorates liver inflammation, steatosis and insulin resistance. Our results suggest therapeutic paradigms for treatment of NAFLD and type 2 diabetes mellitus.

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“…97,98,100,101 While these have real value in illuminating the functions of the various components of the immune system, due to the complexity of the immune system and how real-world exposures may interact with it, in vivo studies are likely to be more reliable indications of real-world effects. 104 Third, some studies on the effects of oral vitamin D exposure are based on protocols that use modest doses of vitamin D. 105,106 While such studies may be safer for participants than studies with larger doses, a stronger signal on effect will undoubtedly be observed through studies that use larger doses. Table 2 includes some of the effects on the immune system of very high-dose vitamin D supplementation in humans from a non-systematically selected subset of studies in the literature.…”

Section: Select Effects Of Vitamin D On the Immune Systemmentioning

confidence: 99%

<p>Elevated Levels of 1,25-Dihydroxyvitamin D in Plasma as a Missing Risk Factor for Celiac Disease</p>

Bittker¹

2020

CEG

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The prevalence of celiac disease (CD) has increased significantly in some developed countries in recent decades. Potential risk factors that have been considered in the literature do not appear to provide a convincing explanation for this increase. This has led some researchers to hypothesize that there is a "missing environmental factor" that increases the risk of CD. Based on evidence from the literature, the author proposes that elevation in plasma levels of 1,25-dihydroxyvitamin D [1,25(OH) 2 D] is a missing risk factor for CD, and relatedly that significant oral vitamin D exposure is a "missing environmental factor" for CD. First, elevated plasma levels of 1,25(OH) 2 D are common in CD, especially in the newly diagnosed. Second, nine distinct conditions that increase plasma levels of 1,25(OH) 2 D are either associated with CD or have indications of such an association in the literature. Third, a retrospective study shows that sustained oral vitamin D supplementation in infancy is associated with increased CD risk, and other studies on comorbid conditions support this association. Fourth, large doses of oral vitamin D upregulate many of the same cytokines, chemokines, and toll-like receptors that are upregulated in CD. Fifth, epidemiological evidence, such as the timing of the inception of a CD "epidemic" in Sweden, the increased prevalence of CD in Finland and the United States in recent decades, the unusually low prevalence of CD in Germany, and the differential in prevalence between Finnish Karelians and Russian Karelians, may all be explained by oral vitamin D exposure increasing CD risk. The same is true of some seemingly contradictory results in the literature on the effects of breastfeeding on CD risk. If future research validates this hypothesis, adjustments to oral vitamin D consumption among those who have genetic susceptibility may decrease the risk of CD in these individuals.

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Effect of vitamin D supplementation on inflammation and nuclear factor kappa-B activity in overweight/obese adults: a randomized placebo-controlled trial

Cited by 41 publications

References 58 publications

Low AMY1 Copy Number Is Cross‐Sectionally Associated to an Inflammation‐Related Lipidomics Signature in Overweight and Obese Individuals

Low AMY1 Copy Number Is Cross‐Sectionally Associated to an Inflammation‐Related Lipidomics Signature in Overweight and Obese Individuals

Vitamin D Receptor Activation in Liver Macrophages Ameliorates Hepatic Inflammation, Steatosis, and Insulin Resistance in Mice

<p>Elevated Levels of 1,25-Dihydroxyvitamin D in Plasma as a Missing Risk Factor for Celiac Disease</p>

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