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

Abstract

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).

Vitamin D Does Not Play a Functional Role in Adipose Tissue Development in Rodent Models

“…The authors observed that 1,25(OH) 2 D 3 redirects mesenchymal lineage progenitor cells toward adipogenesis. Similar findings were observed in studies using human preadipocytes, which differentiated into mature adipocytes in response to 1,25(OH) 2 D 3 treatment . Other in vitro studies showed that 1,25(OH) 2 D 3 was able to inhibit adipogenesis in the mouse preadipocyte cell line 3T3‐L1 .…”

“…Similar findings were observed in studies using human preadipocytes, which differentiated into mature adipocytes in response to 1,25(OH) 2 D 3 treatment. [7,8] Other in vitro studies showed that 1,25(OH) 2 D 3 was able to inhibit adipogenesis in the mouse preadipocyte cell line 3T3-L1. [9,10] In vivo data obtained from vitamin D receptor (Vdr) deficient mice, an animal model that emulates vitamin D deficiency, indicated that these mice developed smaller deposits of subcutaneous and visceral adipose tissues than wildtype (WT) mice.…”

Dipeptidyl peptidase-4 inhibitors and bone metabolism: is vitamin D the link?

“…AT represents not only the main site of vitamin D accumulation in humans, but also a main target of vitamin D action. AT-vitamin D hydroxylases are capable of locally converting this hormone in its active forms [25,26] which display autocrine and paracrine immunoregulatory actions through the specific vitamin D receptor [27,28]. It is plausible, indeed, that chronic DPP4 inhibition modulates AT inflammation and stimulates vitamin D activation/mobilization from adipocytes into the bloodstream.…”

Vitamin D alteration associated with obesity and bariatric surgery

“…28,29 Recently, meta-analyses based on cross-sectional and observational studies strongly suggested that the prevalence of vitamin D deficiency was significantly different between control and obese group. 29,30 Although the cross-sectional studies supported an increase in insulin sensitivity following vitamin D supplementation, 31 the meta-analyses 29,30 did not show any weight reduction in obese patients. Yet, intermediate biomarker of obesity demonstrated an inverse relationship between adiposity and low vitamin D levels.…”