Abstract: TH-PO714
pNaKtide Targeted to Adipocytes Inhibits Na/K-ATPase Reactive Oxygen Species, Systemic Inflammation, and Obesity Development in Mice Fed a Western Diet
Session Information
- Diabetes Mellitus and Obesity: Basic - Experimental - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Diabetes
- 501 Diabetes Mellitus and Obesity: Basic - Experimental
Authors
- Martin, Rebecca, Marshall University School of Medicine, Huntington, West Virginia, United States
- Brickman, Cameron, Marshall University JCESOM, Huntington, West Virginia, United States
- Liu, Jiang, Marshall University JCE School of Medicine, Huntington, West Virginia, United States
- Sodhi, Komal, Marsha, Huntington, West Virginia, United States
- Shapiro, Joseph I., Marshall University School of Medicine, Huntington, West Virginia, United States
Background
Obesity is a worldwide epidemic with many comorbidities. It has been demonstrated that oxidative stress can exacerbate obesity development. We have previously published that systemic administration of pNaKtide, a Na/K-ATPase signaling antagonist, decreased oxidative stress and adipogenesis by blocking Na/K-ATPase signaling mediated amplification of oxidative stress. Adipocyte dysfunction may be prevented by lentiviral mediated adipocyte-specific delivery of pNaKtide.
Methods
C57Bl6 mice were randomly divided into five groups: 1) normal chow 2) normal chow+lenti-adipo-pNaKtide 3) WD 4) WD+lenti-adipo-GFP and 5) WD+lenti-adipo-pNaKtide (n=6-8/group). Lentiviral constructs with pNaKtide driven by an adiponectin promoter were used to achieve pNaKtide expression specifically in adipose tissue. Groups 2 and 5 were given an intraperitoneal injection of lenti-adipo-pNaKtide and group 4 was given an intraperitoneal injection of lenti-adipo-GFP at beginning of the experiment and again at week 2; total time 12 weeks. Body weight was measured weekly. Glucose clearance was determined using an intraperitoneal glucose tolerance test before termination of the experiment. At sacrifice body weight, visceral and subcutaneous fat content of all mice were measured. Blood samples were collected for determination of inflammatory cytokines. Tissues were flash frozen and maintained at -80°C.
Results
Lenti-adipo-pNaKtide significantly reduced WD-induced weight gain, and visceral and subcutaneous fat content. Lenti-adipo-pNaKtide reduced WD-induced changes in glucose tolerance and inflammatory markers TNFα, IL-6 and MCP-1 (p<0.05). An increase in cardiac hypertrophy in WD animals was attenuated (p<0.05). Visceral fat of WD mice expressed higher levels of adipogenic markers PPARγ, FAS, and C/EBP. WD-induced Na/K-ATPase signaling was decreased. Renal function was not significantly impacted; slight decreases in function are evident, suggesting a potential decrease in renal function with chronic obesity.
Conclusion
Collectively this study introduces the novel idea that adipocytes may have a systemic effect. Specifically targeting pNaKtide to the adipocytes with lenti-adipo-pNaKtide ameliorates this systemic effect. This new information is important in the development of new therapeutic targets for obesity.