Uninephrectomy augments the effects of high fat diet induced obesity on gene expression in mouse kidney

Area of Science:

• Nephrology
• Metabolic Research
• Molecular Biology

Background:

• Obesity is an independent risk factor for chronic kidney disease (CKD).
• Reduced nephron number may increase susceptibility to obesity-related renal damage.
• Glomerulosclerosis and renal insufficiency are common consequences of obesity-induced kidney disease.

Purpose of the Study:

• To investigate the relationship between reduced nephron number and susceptibility to obesity-induced renal damage.
• To compare the effects of a high-fat diet (HFD) and uninephrectomy (UNX) on kidney function and gene expression.
• To identify key molecular pathways involved in obesity-related kidney injury.

Main Methods:

• Mice underwent uninephrectomy (UNX) or sham surgery.
• Mice were fed either a normal chow or a high-fat diet (HFD) for 20 weeks.
• Kidney function (albuminuria, glomerulosclerosis, fibrosis, oxidative stress) and gene expression (microarrays) were analyzed.

Main Results:

• HFD induced progressive nephropathy in control mice, characterized by albuminuria, glomerulosclerosis, fibrosis, and oxidative stress.
• These renal pathologies were significantly exacerbated in HFD-fed mice that had undergone UNX.
• Gene expression analysis revealed HFD primarily affected lipid metabolism genes, while UNX+HFD additionally altered cytoskeleton, fibrosis, and hypoxia pathways.

Conclusions:

• High-fat diet-induced kidney damage is more severe in the context of reduced nephron number (post-uninephrectomy).
• Gene expression changes in UNX+HFD mice implicate pathways related to cytoskeleton remodeling, fibrosis, and hypoxia.
• The farnesoid X receptor (FXR) pathway is identified as a potential key mediator in UNX+HFD-induced kidney damage.