title: Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring.
abstract: Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.
authors: School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia. sabiha.chowdhury@unsw.edu.au.
authors: Sabiha S
authors: SS
authors: Chowdhury
authors: School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia. v.lecomte@unsw.edu.au.
authors: Virginie
authors: V
authors: Lecomte
authors: Prince of Wales Clinical School, University of New South Wales, Sydney 2052, NSW, Australia. j.erlich@unsw.edu.au.|Department of Nephrology, Prince of Wales Hospital, Randwick 2031, NSW, Australia. j.erlich@unsw.edu.au.
authors: Jonathan H
authors: JH
authors: Erlich
authors: School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia. c.maloney@unsw.edu.au.
authors: Christopher A
authors: CA
authors: Maloney
authors: School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia. m.morris@unsw.edu.au.
authors: Margaret J
authors: MJ
authors: Morris
mesh_terms: D000818:Animals; D003404:Creatinine / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage*; D004573:Electrolytes / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000008:administration & dosage / Q000097:blood; D008297:Male; D009765:Obesity / Q000235:genetics; D000072740:Paternal Inheritance / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000235:genetics*; D012709:Serum Albumin
chemical_list: D004041:Dietary Fats; D004573:Electrolytes; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D012709:Serum Albumin; D003404:Creatinine
keywords: high fat diet; kidney; obesity; paternal diet; programming; triglyceride