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

• Published in: European journal of nutrition Vol. 51; no. 3; pp. 335 - 342
• Main Authors: Lorente-Cebrián, Silvia, Eriksson, Anna, Dunlop, Thomas, Mejhert, Niklas, Dahlman, Ingrid, Åström, Gaby, Sjölin, Eva, Wåhlén, Kerstin, Carlberg, Carsten, Laurencikiene, Jurga, Hedén, Per, Arner, Peter, Rydén, Mikael
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2012; Springer
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; Adipocytes, White - drug effects; Adipocytes, White - metabolism; Adiponectin - genetics; Adiponectin - metabolism; Adult; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Body Composition - drug effects; Body Mass Index; Calcitriol - pharmacology; Cells, Cultured; Chemistry; Chemistry and Materials Science; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Humans; Inflammation - pathology; Insulin Resistance; Medical sciences; Medicin och hälsovetenskap; Metabolic diseases; Middle Aged; Nutrition; Obesity; Obesity - metabolism; Original Contribution; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Adipocyte; Obesity; Insulin resistance; MCP-1; 1α,25-dihydroxycholecalciferol; Adiponectin; Endocrinopathy; Human; Nutrition; Nutrition disorder; Metabolic diseases; Adipokine; Target tissue resistance; Production; Nutritional status
• ISSN: 1436-6207; 1436-6215; 1436-6215
• DOI: 10.1007/s00394-011-0218-z

Background/aim Obesity is characterized by a low-grade inflammation in white adipose tissue (WAT), which promotes insulin resistance. Low serum levels of 1α,25-dihydroxycholecalciferol (DHCC) associate with insulin resistance and higher body mass index although it is unclear whether vitamin D supplementation improves insulin sensitivity. We investigated the effects of DHCC on adipokine gene expression and secretion in adipocytes focusing on two key factors with pro-inflammatory [monocyte chemoattractant protein-1 (MCP-1/ CCL2 )] and anti-inflammatory [adiponectin ( ADIPOQ )] effects. Methods Pre-adipocytes were isolated from human subcutaneous WAT and cultured until full differentiation. Differentiated adipocytes were either pre-treated with DHCC (10 −7 M) and subsequently incubated with tumor necrosis factor-α (TNFα, 100 ng/mL) or concomitantly incubated with TNFα/DHCC. MCP1 and adiponectin mRNA expression was measured by RT–PCR and protein release by ELISA. Results DHCC was not toxic and did not affect adipocyte morphology or the mRNA levels of adipocyte-specific genes. TNFα induced a significant increase in CCL2 mRNA and protein secretion, while DHCC alone reduced CCL2 mRNA expression (~25%, p  < 0.05). DHCC attenuated TNFα-induced CCL2 mRNA expression in both pre-incubation (~15%, p  < 0.05) and concomitant (~60%, p  < 0.01) treatments. TNFα reduced ADIPOQ mRNA (~80%) and secretion (~35%). DHCC alone decreased adiponectin secretion to a similar degree (~35%, p  < 0.05). Concomitant treatment with DHCC/TNFα for 48 h had an additive effect, resulting in a pronounced reduction in adiponectin secretion (~70%). Conclusions 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.