Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats

Abstract

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment–insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-β was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.

Keywords

• chronic kidney disease
• diabetes
• perirenal adipose tissue
• mesenteric adipose tissue
• experimental model
• Munich Wistar Frömter rat