Adiponectin signaling regulates urinary bladder function by blunting smooth muscle purinergic contractility
Zhaobo Luo, Ali Wu, Simon Robson, Seth L. Alper, Weiqun Yu
Zhaobo Luo, Ali Wu, Simon Robson, Seth L. Alper, Weiqun Yu
View: Text | PDF
Research Article Endocrinology Metabolism

Adiponectin signaling regulates urinary bladder function by blunting smooth muscle purinergic contractility

Abstract

Lower urinary tract symptoms (LUTS) affect approximately 50% of the population over 40 years of age and are strongly associated with obesity and metabolic syndrome. Adipose tissue plays a key role in obesity/metabolic syndrome by releasing adipokines that regulate systemic energy/lipid metabolism, insulin resistance, and inflammation. Adiponectin (ADPN), the most abundant adipokine, modulates energy/metabolism homeostasis through its insulin-sensitizing and antiinflammatory effects. Human plasma ADPN levels are inversely associated with obesity and diabetes. To the best of our knowledge, the role of adipokines such as ADPN in the LUTS associated with obesity/metabolic syndrome remains unknown. We have tested such a possible role in a global ADPN-knockout (Adpn–/–) mouse model. Adpn–/– mice exhibited increased voiding frequency, small voids, and reduced bladder smooth muscle (BSM) contractility, with absence of purinergic contraction. Molecular examination indicated significantly altered metabolic and purinergic pathways. The ADPN receptor agonist AdipoRon was found to abolish acute BSM contraction. Intriguingly, both AMPK activators and inhibitors also abolished BSM purinergic contraction. These data indicate the important contribution of what we believe is a novel ADPN signaling pathway to the regulation of BSM contractility. Dysregulation of this ADPN signaling pathway might be an important mechanism leading to LUTS associated with obesity/metabolic syndrome.

Authors

Zhaobo Luo, Ali Wu, Simon Robson, Seth L. Alper, Weiqun Yu

×

Figure 7

Adpn–/– BSM cells exhibit altered proliferation and differentiation phenotypes.

Options: View larger image (or click on image) Download as PowerPoint
Adpn–/– BSM cells exhibit altered proliferation and differentiation phe...
(A) WT (n = 4) and (B) Adpn–/– (n = 4) bladder tissues immunostained for proliferation marker Ki67 (green, white arrowheads) colocalized with DAPI-stained nuclei (blue). Scale bars: 50 μm. (C–E) Western blots of smooth muscle markers αSMA, SM22, and SMMHC proteins in WT and Adpn–/– bladders (n = 6). (F–H) Body weights, bladder weights, and bladder-to-body weight ratios of male and female WT (n = 9) and Adpn–/– (n = 5) mice. (I) Percentage Ki67-positive cells in BSM layer (WT n = 13 sections; Adpn–/– n = 11 sections), defined by number of Ki67-positive nuclei divided by the number of all nuclei in each randomly selected field imaged by ×40 objective. (J–L) GAPDH-normalized densitometric data from C–E. Data are plotted in box (75% of the data) and whisker format (minimum to maximum), with centerline as median value. Student’s t test, with P values shown above bars. The membrane used for SMMHC detection in E was stripped and reblotted for INSR detection (see Figure 8A) and therefore shares the same loading control.