HEAT TREATED DIET INTAKE DRIVES INTESTINAL PERMEABILITY, COMPLEMENT ACTIVATION AND ALBUMINURIA IN RODENTS

M SNELSON¹, S MIN TAN¹, R CLARKE¹, V THALLAS-BONKE¹, T NGUYEN¹, S PENFOLD¹, B HARCOURT², K SOURRIS¹, R LINDBLOM¹, M ZIEMANN¹, A EL-OSTA¹, M COOPER¹, T WOODRUFF³, C MACKAY¹, J FORBES⁴, M COUGHLAN¹

¹Monash University, ²Murdoch Children’s Research Institute, ³University of Queensland, ⁴Mater Research Institute-The University of Queensland

Aim: This study evaluated the effects of heat-treated diets on kidney injury, intestinal permeability and complement activation in rodents.
Background: Thermally processed food intake has increased dramatically over the past decades, coinciding with increases in CKD. C5a is a major effector molecule of the complement cascade that drives inflammation. The effects of heat-treated diets (HTD) on complement activation and renal injury have not been explored.
Methods: Six-week-old Sprague Dawley rats were randomised to receive a control (CON; AIN93G), HTD (AIN93G baked at 160°C for 1h) or HTD with daily gavage of either 10 mg/kg/d alagebrium chloride (ALA), an inhibitor of advanced glycation end products or daily gavage of 2mg/kg/d PMX-53, a C5a receptor inhibitor for 24 weeks. Six-week-old diabetic mice (db/db) received the CON diet or HTD with or without 12.5% resistant starch (RS) for 10 weeks. Albumin, MCP-1 and C5a were measured by ELISA. Endotoxin was measured using a limulus amoebocyte lysate kit. Intestinal permeability was assessed in vivo by the clearance of FITC-labelled dextran. Transcriptomic profiling of renal cortex was determined by RNA-Sequencing.
Results: The HTD increased albuminuria, plasma endotoxin and MCP-1 which were ameliorated with ALA or PMX-53. HTD increased urinary C5a, which was decreased with ALA. In db/db mice, RS supplementation of the HTD reduced albuminuria and intestinal permeability. Gene set enrichment analysis showed an upregulation in the complement cascade in HTD db/db mice, which was normalized by RS. Similarly, RS supplementation reduced urinary C5a in HTD-fed db/db mice.
Conclusions: These results demonstrate mechanisms by which processed foods cause inflammation that contribute to CKD.

Biography:
Dr Matthew Snelson is a dietitian and researcher interested in the role of diet in altering disease states via modulation of the gut microbiota. He completed his PhD at Monash University in 2019, investigating the effects of a processed diet on gut homeostasis and the contribution that these changes make to the development of diabetic kidney disease. He is currently a Research Fellow in the Department of Diabetes, Monash University investigating the role of resistant starch on the development of diabetic nephropathy.