Hepatic gene expression profiles of healthy adult dogs fed high-fat-low-fiber or low-fat-high-fiber diets

The objective of this experiment was to use microarray technology to generate hepatic gene expression profiles of healthy adult dogs consuming two distinct types of dog food. Six senior (11 years old at baseline) and six weanling (8 weeks old at baseline) female beagles were randomly assigned to either a high-fat-low-fiber diet (diet 1) or a low-fat-high-fiber diet (diet 2). Diet 1 was composed primarily of brewers' rice, chicken byproduct meal, and poultry fat; it contained approximately 28% crude protein, 23% fat, and 5% total dietary fiber. Diet 2 was composed primarily of corn, soybean meal, wheat middlings, and meat and bone meal; it contained approximately 26% crude protein, 11% fat, and 15% total dietary fiber. Dogs remained in the experiment for 12 months. Total cellular UNA was isolated from liver samples using TRIzol (Invitrogen, Carlsbad, CA) and was hybridized to Affymetrix GeneChip Canine Genome Arrays (Affymetrix, Santa Clara, CA) as per the manufacturer's instructions. After microarray normalization procedures, data were analyzed using the mixed-models procedure of SAS (SAS Institute, Cary, NC). Transcripts having a P <.01 (after a false-discovery rate adjustment) and more than twofold change were considered significantly different among groups. Although age-diet interactions were present and the number of transcripts impacted by diet was different in old (176 transcripts) and young (639 transcripts) dogs, many age-independent trends were observed. For example, genes associated with cholesterol and steroid metabolism (e.g., 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase], carboxylesterase, 11-β hydroxysteroid dehydrogenase) and carbohydrate metabolism (e.g., pyruvate kinase, phosphoenolpyruvate carboxykinase (PEPCK), glyceraldehyde 3-phosphate dehydrogenase [GAPDH]) were decreased in both age groups fed diet 1. Other diet-responsive genes included angiotensinogen, taurine transporter, fatty acid-binding protein, glycogen synthetase, plasminogen, fibronectin, and heat shock protein 70. Microarray analysis, as used in this study, allows global assessment of metabolic status. Nutritionists may use this technology to identify gene-nutrient interactions important to canine metabolism and health. In this study, we detected numerous gene expression differences attributable to diet and age. Overall, young dogs were more responsive to dietary changes than old dogs. Dogs fed a low-fat-high-fiber diet also had a more dramatic response to fasting conditions. The information from this study provides a platform for further nutrigenomic research focused on understanding the unique dietary needs of geriatric dogs.