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Abstract: FR-PO1121

Dissecting the Role of Adipocyte Na-K-ATPase Signaling in Attenuating Experimental Uremic Cardiomyopathy by Adipose Tissue Transplantation

Session Information

  • Transplantation: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1901 Transplantation: Basic

Author

  • Sodhi, Komal, Marshall University Joan C. Edwards School of Medicine, Huntington, West Virginia, United States
Background

Adipocytes contribution to systemic disease has become an important topic. We have recently demonstrated that administration of NaKtide, antagonist of Na/K-ATPase (NKA) signaling, coupled to adipocyte specific promoter adiponectin can improve adipocyte phenotype. In experimental uremic cardiomyopathy, uremic toxin exposure of adipocyte will generate ROS, subsequently activating adipocyte NKA signaling and causing adipocyte dysfunction, cytokine production, and systemic oxidative stress. Studies have shown that transplanting brown adipose tissue from C57BL6 mice reduced obesity and improved whole energy metabolism. Based on these observations, we hypothesize that the transplantation of NaKtide transfected subcutaneous fat tissues into mice with partial nephrectomy (PNx) will improve adipocyte phenotype and attenuate uremic cardiomyopathy.

Methods

Following 4 weeks of PNx or Sham surgery and lenti-adiponectin-Naktide treatment, 300mg of fat pads (Sham, Sham+NaKtide, and PNx+NaKtide groups) were subcutaneously transplanted into strain- and age- matched donor littermates in the dorsal interscapular region of PNx mice. Following 4 weeks after transplantation, tissues were harvested for morphological and molecular analyses.

Results

Histological analysis of cardiac tissue shows increased fibrosis with PNx, which was decreased with transplantation of adipose tissue from mice treated with NaKtide (p≤0.01). PNx mice developed cardiomyopathy characterized by increased heart weight and decreased cardiac function, assessed by echocardiography measurements, as compared to Sham operated mice (p<0.01). These alterations were reversed in PNx mice, by the transplantation of NaKtide transfected adipose tissues from PNx+NaKtide donor mice (p<0.01). Our results also showed that NaKtide transfected adipose tissue from PNx+NaKtide mice, transplanted to PNx recipient mice improved glucose tolerance, hematocrit levels and levels of plasma inflammatory cytokines, including TNFα, IL-6 and MCP-1.

Conclusion

Our study demonstrates that adipocytes contribute to the oxidant stress associated with uremic cardiomyopathy by activation of NKA signaling, which is improved by the subcutaneous fat transplantation transfected with NaKtide. These data suggest that the adipocyte NKA signaling may be a viable clinical target for the prevention or treatment of uremic cardiomyopathy.

Funding

  • Other NIH Support