Uncoupling Protein 1 Expression In Adipose Tissue Research Articles

Effects of growth hormone on uncoupling protein 1 in white adipose tissues in obese mice

ObjectiveThe transition of white adipocytes to beige cells (a phenomenon referred to as browning or beigeing) during obesity has been previously reported. Our study aimed to examine the mechanisms through which obesity induced by a high fat diet (HFD) affects uncoupling protein 1 (UCP1) expression via signal transduction and activator of transcription 5 (STAT5s). DesignSeven-week-old male C57BL/6J mice were fed a normal or HFD for 11weeks. Body weight, white adipose tissue weight, and blood lipid and glucose levels were measured. To unveil the molecular mechanisms of UCP1 expression in adipose tissue, we performed further studying 3T3-L1 cells using qRT-PCR. We also measured UCP1 promoter activity in the TSA201 cell line using a dual luciferase assay. In addition, we analyzed the predicted consensus sequences for STAT5 binding in the UCP1 promoter region. ResultsMice fed an HFD had higher body weight and intra-abdominal adipose tissues weight and a higher expression of UCP1, GH receptor (GHR), STATs, suppressors of cytokine signaling (SOCSs), and cytokine-inducible SH2-containing protein (CISH) compared to control mice. In 3T3-L1 cell studies, GH induced phosphorylation of the STAT5, SOCSs, CISH and UCP1 expressions. UCP1 promoter activity was associated with constitutively active STAT5 in a dose-dependent manner. We confirmed functional STAT5 binding sites at −425, −279, and −178bp of the UCP1 promoter. ConclusionWe suggest that endogenous GH induces UCP1 expression in adipose tissue via STAT5.

Proinflammatory cytokine interleukin-1β suppresses cold-induced thermogenesis in adipocytes

In this study, we investigated the effects of interleukin-1β (IL-1β), a typical proinflammatory cytokine on the β-adrenoreceptor-stimulated induction of uncoupling protein 1 (UCP1) expression in adipocytes. IL-1β mRNA expression levels were upregulated in white adipose tissues of obese mice and in RAW264.7 macrophages under conditions designed to mimic obese adipose tissue. Isoproterenol-stimulated induction of UCP1 mRNA expression was significantly inhibited in C3H10T1/2 adipocytes by conditioned medium from lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in comparison with control conditioned medium. This inhibition was significantly attenuated in the presence of recombinant IL-1 receptor antagonist and IL-1β antibody, suggesting that activated macrophage-derived IL-1β is an important cytokine for inhibition of β-adrenoreceptor-stimulated UCP1 induction in adipocytes. IL-1β suppressed isoproterenol-induced UCP1 mRNA expression in C3H10T1/2 adipocytes, and this effect was partially but significantly abrogated by inhibition of extracellular signal-regulated kinase (ERK). IL-1β also suppressed the isoproterenol-induced activation of the UCP1 promoter and transcription factors binding to the cAMP response element. Moreover, intraperitoneal administration of IL-1β suppressed cold-induced UCP1 expression in adipose tissues. These findings suggest that IL-1β upregulated in obese adipose tissues suppresses β-adrenoreceptor-stimulated induction of UCP1 expression through ERK activation in adipocytes.