Differential effects of 1α,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes

Lorente‐Cebrián, Silvia; Eriksson, Anna; Dunlop, Thomas W.; Mejhert, Niklas; Dahlman, Ingrid; Åström, Gaby; Sjölin, Eva; Wåhlén, Kerstin; Carlberg, Carsten; Laurencikiene, Jurga; Hedén, Per; Arner, Peter; Rydén, Mikael

doi:10.1007/s00394-011-0218-z

Cited by 71 publications

(65 citation statements)

References 45 publications

(47 reference statements)

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“…23 Most likely, the hydroxylation of VD in AT is of importance to AT itself, as it allows for autocrine/ paracrine actions of VD. 54,55 Our findings of differential expression of the VDR and CYP27B1 in lean and obese women warrants further investigations on the autocrine/paracrine actions of VD in different compartments of AT.…”

Section: Discussionmentioning

confidence: 82%

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

et al. 2012

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OBJECTIVE: Low vitamin D (VD) levels are common in obesity. We hypothesized that this may be due to metabolism of VD in adipose tissue (AT). Thus, we studied (1) whether the VD-metabolizing enzymes were expressed differently in AT of lean and obese individuals and in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and (2) whether their expression was influenced by weight loss. METHODS: Samples of SAT and VAT were analyzed for expression of the vitamin-D-25-hydroxylases CYP2R1, CYP2J2, CYP27A1 and CYP3A4, the 25-vitamin-D-1a-hydroxylase CYP27B1, the catabolic vitamin-D-24-hydroxylase CYP24A1, and the vitamin D receptor, using reverse transcriptase-PCR. Moreover, plasma 25-hydroxy-vitamin D (25OHD) level was measured and related to the expression of these enzymes. Samples of SAT and VAT from 20 lean women and 20 obese women, and samples of SAT from 17 obese subjects before and after a 10% weight loss were analyzed. RESULTS: A plasma 25OHD level o50 nmol l À 1 was highly prevalent in both lean (45%) and obese (90%) women (Po0.01). Plasma 25OHD increased by 27% after weight loss in the obese individuals (Po0.05). Expression levels of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 were decreased by 71% (Po0.0001) and 49% (Po0.05), respectively, in SAT of the obese. CYP24A1 did not differ between lean and obese women, but the expression was increased by 79% (Po0.05) after weight loss. CONCLUSION: Obesity is characterized by a decreased expression of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 in SAT, whereas the catabolic CYP24A1 does not differ between lean and obese women. However, the expression of CYP24A1 is increased after weight loss. Accordingly, AT has the capacity to metabolize VD locally, and this can be dynamically altered during obesity and weight loss. INTRODUCTIONLow levels of circulating 25-hydroxy-vitamin D (25OHD) are associated with increased fat mass and body mass index, 1-5 but the underlying mechanism for this association is not fully elucidated. 6 Vitamin D (VD) is stored in adipose tissue (AT), and release of VD from AT is proposed to serve as an endogenous source of VD during the winter, when cutaneous production is low or absent in several parts of the world. 7 As low circulating levels of 25OHD are common in association with the obese state, 8 several studies have examined the effect of weight loss on circulating levels of 25OHD. However, results are inconsistent. After diet-and exercise-induced weight loss, both increased 9-11 and unaltered 12,13 circulating levels of 25OHD have been reported. Likewise, after major weight loss by bariatric surgery, both temporary 14-16 and long-term increases [16][17][18] in circulating levels of 25OHD have been reported, along with reports of no changes one year after surgery. 13,19 Taken together, these findings indicate that body weight is an important factor for circulating 25OHD levels. Several other explanations for the low levels of 25OHD in obesity have been proposed: a decreased exposure to sun light, 20 ...

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Section: Discussionmentioning

confidence: 82%

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

et al. 2012

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“…These results have since been challenged by several groups (67,(75)(76)(77) who consistently report anti-inflammatory effects of 1,25 (OH) 2 D whatever the model studied, which fits better with the well-described anti-inflammatory effect of VD in many other cell types (78) . Indeed, it was shown that 1,25(OH) 2 D significantly decreased the release of IL-8, monocyte chemoattractant protein (MCP)-1 and IL-6 by human preadipocytes (76) and MCP-1 by human adipocytes (75) . These anti-inflammatory effects were associated with inhibition of the NF-κB signalling pathway (77) .…”

Section: Regulation Of Inflammationmentioning

confidence: 79%

Vitamin D modulates adipose tissue biology: possible consequences for obesity?

et al. 2015

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Cross-sectional studies depict an inverse relationship between vitamin D (VD) status reflected by plasma 25-hydroxy-vitamin D and obesity. Furthermore, recent studies in vitro and in animal models tend to demonstrate an impact of VD and VD receptor on adipose tissue and adipocyte biology, pointing to at least a part-causal role of VD insufficiency in obesity and associated physiopathological disorders such as adipose tissue inflammation and subsequent insulin resistance. However, clinical and genetic studies are far less convincing, with highly contrasted results ruling out solid conclusions for the moment. Nevertheless, prospective studies provide interesting data supporting the hypothesis of a preventive role of VD in onset of obesity. The aim of this review is to summarise the available data on relationships between VD, adipose tissue/adipocyte physiology, and obesity in order to reveal the next key points that need to be addressed before we can gain deeper insight into the controversial VD-obesity relationship.Adipose tissue: Vitamin D: Obesity: Inflammation: Adipocytes: Nutrients: Nutrition Vitamin D: a brief overview Vitamin D (VD; calciferol) is a hormone mainly described for its role as a regulator of phosphate and calcium homeostasis (1) . It can be obtained through animal (VD 3 , cholecalciferol) or plant (VD 2 , ergocalciferol) food sources. Only a few foodstuffs contain significant amounts of VD, the main sources being fish liver oils, fatty fish (sardines, herring and mackerel) and egg yolk (2,3) , but small quantities are also found in fortified milk, orange juice, bread and cereals. Alternatively, VD 3 is produced endogenously in the skin after UVB irradiation from the precursor 7-dehydrocholesterol to give pre-VD 3 , which is further isomerised to VD 3 before being released into the circulation (4) . Classical estimates have assigned a majority (70-90 %) of VD supply to dermal synthesis, but a recent paper revised this figure down to just 10-25 % of VD supply (5) and posited that dietary intake of 25-hydroxy-vitamin D (25(OH)D) is a significant contributor to total VD input.Adipose tissue is a major storage site for vitamin D Despite limited data, it is widely accepted that adipose tissue is a reservoir for VD in human subjects and rats (6)(7)(8)(9)(10) . Interestingly, visceral fat was found to contain 20 % more VD than subcutaneous fat (11) . Heaney et al. (12) calculated that 65 % of total VD in the body is in the form of D 3 , for which adipose tissue and skeletal muscle appear to be the main body stores (accounting for 73 and 16 %, respectively).

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“…Indeed, several studies have reported the impact of VD on inflammation, with some discordance. Initial studies investigating the effects of VD on adipocytes (from murine and human origin) reported a proinflammatory effect (13,14), whereas several other studies have reported an antiinflammatory effect of VD on adipocytes (15)(16)(17)(18), consistent with the anti-inflammatory effect of VD in many other cell types (19).…”

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confidence: 83%

“…Indeed, 1,25(OH) 2 D (the active form of vitamin D) significantly decreased the release of IL8, CCL2 and IL6 in human preadipocytes (16) and CCL2 in human adipocytes (15) induced through proinflammatory stimuli, such as macrophage-conditioned medium, TNF␣ and IL1␤. In addition, 1,25(OH) 2 D decreased the preadipocyte-induced monocyte migration of THP-1 monocytes (16).…”

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confidence: 99%

Vitamin D Limits Chemokine Expression in Adipocytes and Macrophage Migration In Vitro and in Male Mice

et al. 2015

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Vitamin D (VD) displays immunoregulatory effects and reduces adipocyte inflammation, which may participate to a reduction of adipose tissue macrophage infiltration in the context of obesity-associated low-grade inflammation. These observations have been described mainly in vitro, through the evaluation of a limited number of inflammatory markers. Here, we studied the effects of 1,25 dihydroxy-VD on chemokine network expression in adipocytes (by transcriptomic approach), and we confirm the physiological relevance of these data in vivo, by demonstrating the effect of VD on cytokine and chemokine gene expression as well as on macrophage infiltration in adipose tissue. 1,25 dihydroxy-VD down-regulated (-1.3- to -10.8-fold) the mRNA expression of 29 chemokines and limited macrophage migration in TNFα-conditioned adipocyte medium (1.5-fold; P < .05). This effect was associated with a reduction in p65 and IκB (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) phosphorylation (2-fold compared with TNFα; P < .05). The effects of VD were confirmed in mice injected ip with lipopolysaccharide (acute inflammation) and diet-induced obese mice (metabolic inflammation), where the levels of mRNA encoding proinflammatory cytokines and chemokines (∼2-fold) were reduced in adipocytes (acute and metabolic inflammation) and adipose tissue and that macrophage infiltration was also inhibited in the adipose tissue of obese mice (metabolic inflammation). Altogether, these results showed that VD displayed a global immunoregulatory impact on adipocytes, notably via the inhibition of chemokine expression and macrophage infiltration in inflamed adipose tissue.

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Differential effects of 1α,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes

Abstract: DHCC attenuates MCP-1 and adiponectin production in human adipocytes, thereby reducing the expression of both pro- and anti-inflammatory factors. These effects may explain the difficulties so far in determining the role of DHCC in insulin sensitivity and obesity in humans.

Cited by 71 publications

References 45 publications

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

Vitamin D modulates adipose tissue biology: possible consequences for obesity?

Vitamin D Limits Chemokine Expression in Adipocytes and Macrophage Migration In Vitro and in Male Mice

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