Vitamin D reduces the inflammatory response and restores glucose uptake in adipocytes.
METHODS
Obesity is strongly associated with low-grade inflammation, notably due to an overproduction of proinflammatory markers by adipose tissue and adipocytes as well as a vitamin D deficiency. Whether these problems are interrelated has not been clearly established.


RESULTS
In the present report, decreases in the levels of inflammatory markers such as IL-6, MCP-1, and IL-1β (mRNA and protein level) in human adipocytes and in 3T3-L1 adipocytes were observed after 1,25-dihydroxyvitamin D3 (1,25-(OH)(2) D(3) ) treatment. Such treatment also decreased the expression of the TNF-α-mediated proinflammatory marker in 3T3-L1 and human adipocytes. A similar effect was observed in adipocyte-macrophage co-culture systems in which 1,25-(OH)(2) D(3)  decreased proinflammatory marker expression under basal and TNF-α-stimulated conditions. The involvement of VDR and NF-κB was confirmed in these regulations. Incubation with 1,25-(OH)(2) D(3)  also resulted in the dephosphorylation of p38, which is linked to the transcriptional induction of several Dusp family members. Functional consequences of the 1,25-(OH)(2) D(3)  treatment on glucose uptake and AKT phosphorylation were observed.


CONCLUSIONS
The improvement of both proinflammatory status and glucose uptake in adipocytes under 1,25-(OH)(2) D(3)  effect suggests that low-grade inflammation could be linked to vitamin D deficiency. This observation offers new perspectives in the context of obesity and associated physiopathological disorders.
INRA, UMR1260, Marseille, France.
Julie
J
Marcotorchino
Erwan
E
Gouranton
Beatrice
B
Romier
Franck
F
Tourniaire
Julien
J
Astier
Christiane
C
Malezet
Marie-Josèphe
MJ
Amiot
Jean-François
JF
Landrier
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014807:Vitamin D / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D014807:Vitamin D; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose