Adipocytes play an etiological role in the podocytopathy of high-fat diet-fed rats

Abstract

Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy.

Metabolic dysregulation accelerates injury‐induced joint degeneration, driven by local inflammation; an in vivo rat study

“…It remains unclear whether this osteophyte formation itself can cause further joint degeneration and cartilage loss or is the consequence. After HF diet feeding systemic metabolic alterations are known to increase the fat content, alter adipocytes size and stimulate their pro‐inflammatory cytokine production such as tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6 . These cytokines are not only produced systemically but also locally by different tissues in OA knee joints including the infrapatellar fat pad and the synovial membrane .…”

“…After HF diet feeding systemic metabolic alterations are known to increase the fat content, alter adipocytes size and stimulate their pro-inflammatory cytokine production such as tumor necrosis factor-a, interleukin-1b, and interleukin-6. [45][46][47] These cytokines are not only produced systemically but also locally by different tissues in OA knee joints including the infrapatellar fat pad and the synovial membrane. 6,18,48 In most tissues macrophages are a significant source of inflammatory cytokines, were both BMI and adipocyte size were strong predictors of the percentage of CD68-expressing macrophages.…”

Purinergic 2X7 Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome

“…It has been generally recognized that podocyte damage and dysfunction play a pivotal role in the occurrence and progression of ORG. [ 11 12 13 22 ]…”

“…Accumulating data have shown that hyperleptinemia often occurred in obese individuals and could induce a lot of pathophysiologic responses which were involved in the inflammatory effect and kidney damage, including podocyte damage, of ORG. [ 12 13 23 24 25 26 ] Therefore, leptin was selected as the inducer to the established cell model in this study. Both animal and cell models provided this study with good platforms for research of pathogenic mechanism of ORG in vivo and in vitro .…”

“…The podocyte-associated molecules detected in this study included nephrin, podocin, and desmin (a sensitive marker of podocyte damage[ 13 ]). Real time-PCR and Western blot assay, which were conducted using the RNA and protein extracted from renal cortex tissue, showed that the mRNA and protein expression of nephrin (mRNA: t = 8.711, P < 0.01; protein: t = 8.501, P < 0.01) and podocin (mRNA: t = 4.143, P < 0.01; protein: t = 6.678, P < 0.01) were significantly downregulated, and the mRNA (t = −8.574, P < 0.01) and protein (t = −5.161, P < 0.01) expression of desmin were significantly upregulated in the model group, compared with that of the control group [ Figure 3 ].…”