Distribution of renal medullary hyaluronan in lean and obese rabbits

Abstract

Background: Obese individuals have an expanded interstitium in the renal inner medulla (IM), which stains positively with periodic acid-Schiff and Alcian blue. In obese dogs, the IM is also expanded, with hyaluronan (HA) content being 2.4 times control.

Methods: We determined the anatomic pattern of renal HA deposition following weight gain, using an animal model of obesity consisting of young rabbits (N = 10), representing animals entering into the study, lean rabbits (N = 19), fed a control diet, and obese rabbits (N = 19), fed a high-fat diet (15% fat, by fortifying with corn oil and lard, in a ratio of 2:1) for two to three months. Tissue was papain digested, and HA was recovered in a phosphate or a Tris buffer and detected by an indirect immunoabsorbent competition assay.

Results: Rabbits fed a high-fat diet for 8 to 12 weeks gained weight (37%) and became mildly hypertensive (10 mm Hg). In lean rabbits, HA was low in the renal cortex (6 +/- 30 microg/g tissue), increased steadily across the outer medulla (OM; 79 +/- 28 microg/g tissue) and was uniformly high in the IM (192 +/- 28 microg/g tissue) when recovered in a Tris buffer; these levels of tissue HA did not change during the three-month period of dietary intervention. In obese rabbits, the renal medullary interstitium was expanded and stained intensely with periodic acid Schiff and Alcian blue, and tissue HA was elevated in the IM (448 +/- 25 microg/g tissue) but not the cortex (5 +/- 25 microg/g tissue) or the OM (85 +/- 25 microg/g tissue). The significant difference was due to those IM samples taken from the renal papilla; IM samples from the body of the kidney did not significantly differ among the lean, obese, and young rabbits.

Conclusion: The elevated renal HA associated with weight gain is limited to the IM and occurs most consistently in the papilla, which is the region of the kidney that is most vulnerable to distention caused by elevated renal interstitial hydrostatic pressure.