A possible inflammatory role of twist1 in human white adipocytes.
OBJECTIVE
Twist1 is a transcription factor that is highly expressed in murine brown and white adipose tissue (WAT) and negatively regulates fatty acid oxidation in mice. The role of twist1 in WAT is not known and was therefore examined.


METHODS
The expression of twist1 was determined by quantitative real-time PCR in different tissues and in different cell types within adipose tissue. The effect of twist1 small interfering RNA on fatty acid oxidation, lipolysis, adipokine secretion, and mRNA expression was determined in human adipocytes. The interaction between twist1 and specific promoters in human adipocytes was investigated by chromatin immunoprecipitation (ChIP) and reporter assays.


RESULTS
Twist1 was highly expressed in human WAT compared with a set of other tissues and found predominantly in adipocytes. Twist1 levels increased during in vitro differentiation of human preadipocytes. Gene silencing of twist1 in human white adipocytes had no effect on lipolysis or glucose transport. Unexpectedly, and in contrast with results in mice, twist1 RNA interference reduced fatty acid oxidation. Furthermore, the expression and secretion of the inflammatory factors tumor necrosis factor-alpha, interleukin-6, and monocyte chemoattractant protein-1 were downregulated by twist1 silencing. ChIP and reporter assays confirmed twist1 interaction with the promoters of these genes.


CONCLUSIONS
Twist1 may play a role in inflammation of human WAT because it can regulate the expression and secretion of inflammatory adipokines via direct transcriptional effects in white adipocytes. Furthermore, twist1 may, in contrast to findings in mice, be a positive regulator of fatty acid oxidation in human white adipocytes.
Pettersson
Amanda T
AT
Karolinska Institutet, Department of Medicine, Huddinge, Lipid Laboratory, NVS, Stockholm, Sweden. amanda.pettersson@ki.se
Laurencikiene
Jurga
J
Mejhert
Niklas
N
Näslund
Erik
E
Bouloumié
Anne
A
Dahlman
Ingrid
I
Arner
Peter
P
Rydén
Mikael
M
D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D000818:Animals; D002250:Carbon Radioisotopes; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D017930:Genes, Reporter; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008066:Lipolysis / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010084:Oxidation-Reduction; D010168:Palmitates / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000502:physiology; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
C499918:ADIPOQ protein, human; D052242:Adiponectin; C111835:CCL2 protein, human; D002250:Carbon Radioisotopes; D018932:Chemokine CCL2; C508600:IL6 protein, human; D015850:Interleukin-6; D009687:Nuclear Proteins; D010168:Palmitates; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D014409:Tumor Necrosis Factor-alpha; D051879:Twist-Related Protein 1