Expression Of Beta3-adrenergic Receptors Research Articles

The effect of aerobic exercise training on gene expression of beta3-adrenergic receptor and beta-arrestin2 in inguinal white adipose tissue of mice fed with a high fat diet

Background and aims: Beta-adrenergic signaling deficiency has been established to be related to obesity and related diseases. Beta3- adrenergic receptor (Adrb3) and beta-arrestin2 (Barr2) are pivotal agents in the beta-adrenergic-signaling pathway. This study aimed to investigate the preventive effect of aerobic training on dysregulation of Adrb3 and Barr2 gene expression that was induced by high-fat diet (HFD) in inguinal white adipose tissue of mice. Materials and Methods: Twenty-one C57BL/6 mice were assigned to three groups as follows: 1) control group (n=7), 2) high-fat diet-induced overweight (HFD-OW) (n=7), and 3) high-fat diet with aerobic training (HFD-AT) (n=7). The HFD-OW group were fed with a HFD for 12 weeks. The HFD-AT group had aerobic training for six weeks on a treadmill in addition to feeding with the HFD. The real-time polymerase chain reaction (PCR) method was used to measure the gene expression of Adrb3 and Barr2 in inguinal white adipose tissue. Results: The gene expression of Adrb3 did not significantly change between groups (P>0.05). However, the expression of Barr2 in HFD-OW group was significantly increased as compared to the control group (1.5-fold: P=0.001). Interestingly, the Barr2 expression in HFD-AT group was significantly lower compared with HFD-OW group (P=0.045). Conclusion: The results indicated that aerobic training could inhibit the upregulation of Barr2 induced by HFD. It seems that a portion of the preventive effect of aerobic training on the development of obesity may be mediated by inhibiting the Barr2 expression in adipose tissue.

534 - Dysregulation of phospholamban and beta 3-adrenergic receptor expression might lead to bladder detrusor overactivity via SERCA inhibition

534 - Dysregulation of phospholamban and beta 3-adrenergic receptor expression might lead to bladder detrusor overactivity via SERCA inhibition

Research progress of beta3-adrenergic receptor in heart

The expression of beta3-adrenergic receptor(β3-AR) is very low in the physiological state of the heart, but increases in the pathological state of heart failure.Due to the negative inotropic effect when stimulating β3-AR, the early researchers believed that the increase of β3-AR in the pathological state would aggravate the cardiac function, but the later researches of beta3-AR on heart failure found a contrary conclusion.More and more evidence suggests that beta3-AR may play a useful role in the cardiovascular system, which making beta3-AR to be a new target for the treatment of cardiovascular disease.This article reviewed the progress of the above researches. Key words: beta3-Adrenergic receptor; Heart

Thermogenesis, fatty acid synthesis with oxidation, and inflammation in the brown adipose tissue of ob/ob (−/−) mice

Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57Bl/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57Bl/6 background strain), at three months of age (n=10/group). At euthanasia, animals had their interscapular BAT weighed, and prepared for analysis (Western blot, and RT-qPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1). The ob/ob group also showed impaired gene expression for lipid utilization (perilipin was increased, while other markers were diminished: carnitine palmitoyltransferase-1b, CPT-1b; cluster of differentiation 36, CD36; fatty acid binding protein 4, FABP4; fatty acid synthase, FAS, and sterol regulatory element-binding protein 1c, SREBP1c), and altered protein expression of insulin signaling (diminished pAKT, TC10, and GLUT-4). Lastly, the ob/ob group showed increased gene expression of markers of inflammation (interleukin 1 beta, IL-1beta; IL-6, tumor necrosis factor alpha, TNFalpha; and monocyte chemotactic protein-1, MCP-1). In conclusion, the ob/ob mice have decreased thermogenic markers associated with reduced gene expression related to fatty acid synthesis, mobilization, and oxidation. There were also alterations in insulin signaling and protein and gene expressions of inflammation. The findings suggest that the lack of substrate for thermogenesis and the local inflammation negatively regulated thermogenic signaling in the ob/ob mice.

Impact of rosiglitazone on the expression of β3-AR in the stable cell lines expressed β3-AR gene

The aim of the present study was to investigate the effect of rosiglitazone, a peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2) agonist, on the expression of beta3-adrenergic receptor (beta3-AR) at transcriptional and translational level. We cloned the cDNA sequences of human PPAR-gamma2 (hPPAR-gamma2) gene and human wild type and mutant beta3-adrenergic receptor (hbeta3-AR) genes and established their eukaryotic expression vectors. The pcDNA3.1/hbeta3-AR (mutant and wild type) was transfected into SH-SY5Y cells using electroporation method. The expression level of beta3-AR protein was determined by Western blot analysis. Our results showed that the reverse transcription-PCR products were consistent with theoretical fragment sizes of human PPAR-gamma2 (1544 bp) and human beta3-AR genes (1578 bp). The sequence analysis of PPAR-gamma2 and beta3-AR genes showed that the fragment sizes were the same as that of human PPAR-gamma2 and human beta3-AR genes in Genbank. The pcDNA3.1/hbeta3-AR (mutant and wild type) was successfully cloned to SH-SY5Y cells. We found that the expression of beta3-AR protein was significantly inhibited by rosiglitazone in a concentration-dependent manner in SH-SY5Y cell lines stably expressed beta3-AR genes. The results suggest that rosiglitazone has a concentration-dependent inhibitory effect on the expression of beta3-AR protein, and this inhibitory effect may be due to activation of PPAR-gamma2 receptor.

β3-Adrenergic Receptors Regulate Retinal Endothelial Cell Migration and Proliferation

Sympathetic nerves may play a role in vascular disorders of the eye. In the present study, we hypothesized that activation of beta3-adrenergic receptors on retinal endothelial cells would promote migration and proliferation of these cells, two markers of an angiogenic phenotype. We show, for the first time, expression of beta3-adrenergic receptors on cultured retinal endothelial cells. Activation of these receptors with BRL37344, a specific beta3-adrenergic receptor agonist, promoted migration that was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K), the mitogen activated protein kinase component MEK, and matrix metalloproteinases (MMPs) 2 and 9. BRL37344 stimulated proliferation, which could be blocked by inhibitors of Src, PI3K, and MEK. These cells also express the beta1-adrenergic receptor with no beta2-adrenergic receptor expression observed. Stimulation of the beta1-adrenergic receptor with xamoterol, a specific partial agonist, did not promote proliferation or migration. These results support the hypothesis that beta3-adrenergic receptors play a role in proliferation and migration of cultured human retinal endothelial cells.

Apparent lack of beta 3-adrenoceptors and of insulin regulation of glucose transport in brown adipose tissue of guinea pigs

Norepinephrine-induced thermogenesis was substantial in adipocytes from brown adipose tissue (BAT) of cold-acclimated guinea pigs but absent in adipocytes from BAT of warm-acclimated guinea pigs. There was no thermogenic response to any beta 3-adrenergic agonist (CL-316,243, ZD-7114, BRL-28410, CGP-12177). The receptor was characterized as a beta 1-adrenoceptor. Adrenergic agonists stimulated adenylate cyclase in membranes from BAT of both warm- and cold-acclimated guinea pigs also via a beta 1-adrenoceptor; beta 3-adrenergic agonists had no effect. Glucose transport by brown adipocytes from warm-acclimated guinea pigs was not stimulated by either norepinephrine or insulin. Cold acclimation induced the appearance of stimulation of glucose transport by norepinephrine in association with the appearance of a large capacity for thermogenesis, but there was little improvement in response to insulin. GLUT4 was present in membranes from BAT of both warm- and cold-acclimated guinea pigs. Insulin is known to have an antilipolytic effect on both BAT and white adipose tissue of guinea pigs. Thus there is a selective lack of insulin-regulated glucose transport that is not improved by cold acclimation. Guinea pigs may have a mutated component of the translocation mechanism for GLUT4. beta 3-Adrenoceptors appear to be absent in brown adipocytes of adult guinea pigs, as in white adipocytes of guinea pigs, yet are known to be present in the gut. Tissue-specific expression of beta 3-adrenergic receptors in guinea pigs may differ from that in rats, in which receptors are expressed in the adipose tissues and gut.