Kidney Week

Abstract: FR-PO1192

Six Months of High-Fat Diet and Physical Inactivity in Thermoneutrality Are Insufficient to Cause CKD in Mice

Session Information

• CKD: Mechanisms - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Opurum, Precious Chinonyerem, University of Utah Health, Salt Lake City, Utah, United States

Precious Chinonyerem Opurum, PhD

• Decker, Stephen, University of Utah Health, Salt Lake City, Utah, United States

Stephen Decker, PhD

• Stuart, Deborah, University of Utah Health, Salt Lake City, Utah, United States

Deborah Stuart

• Peterlin, Alek D., University of Utah Health, Salt Lake City, Utah, United States

Alek D. Peterlin, MS

• Paula, Venisia L., University of Utah Health, Salt Lake City, Utah, United States

Venisia L. Paula

• Sanchez, Alejandro, University of Utah Health, Salt Lake City, Utah, United States

Alejandro Sanchez, MD

• Ramkumar, Nirupama, University of Utah Health, Salt Lake City, Utah, United States

Nirupama Ramkumar, MD, MPH, FASN

• Funai, Katsuhiko, University of Utah Health, Salt Lake City, Utah, United States

Katsuhiko Funai, PhD

Background

Chronic kidney disease (CKD) is a progressive disorder marked by a decline in kidney function. The process by which obesity and sedentary behavior contribute to the development of CKD is poorly understood. Studies suggest a decline in mitochondrial function likely contributes to the pathogenesis of CKD, but the detailed mechanisms remain unclear. This knowledge gap is contributed to by a lack of a murine CKD model that does not rely on injury, toxin, or gene deletion to induce reduced kidney function.

Methods

Here, we employed a recently published model of sedentariness developed in our lab, which phenocopies many of the systemic metabolic adaptations that occur in human sedentary behavior. Wildtype C57BL/6J male mice housed under ambient (22°C) or thermoneutral conditions (29°C) were fed standard chow or Western high-fat diet (HFD) with or without small mice cage (SMC) intervention for 6 months.

Results

However, while HFD or SMC tended to increase the glomerular filtration rate (GFR), these interventions were insufficient to cause CKD. Histological and gene expression data suggested a potential early onset of fibrosis programming, but the magnitudes of these changes were minor. High-resolution respirometry and fluorometry experiments showed increases in mitochondrial respiration and ATP synthesis capacities, also likely demonstrating early adaptive responses to heightened kidney burden.

Conclusion

Given the long duration of the intervention, these data reinforce the technical challenge associated with modeling CKD in mice. They also suggest that metabolic pressures caused by obesogenic diet and/or sedentariness may be insufficient to robustly negatively influence kidney function.

Funding

• NIDDK Support