PSIII-25 Adipose gene expression of mature neutered male cats during the transition from a lean to an obese phenotype

Abstract

Abstract Obesity is the most prevalent disease in companion animals. Feline pets have access to palatable and nutrient dense foods and often live a sedentary lifestyle leading to a positive energetic balance. Obese companion cats are more predisposed to suffer from insulin resistance and diabetes. This study examined changes in abdominal subcutaneous adipose tissue over a 36-wk course of ad libitum feeding to provide insights into early gene regulation in metabolic pathways associated with weight gain and metabolic dysfunction. Nine neutered male cats (mean age 8 ± 0.3 yr) were fed to maintain ideal BW at baseline (wk 0), and then fed ad libitum for 36 wk. At wk 0, 12, 24, and 36, biopsies were collected from subcutaneous adipose deposits of the abdomen. RNA was isolated using a commercially available extraction kit specific for lipids (RNeasy lipid tissue mini kit, Qiagen). mRNA expression of over 40 genes encoding adipokines, transcription factors, glucose transporters, inflammatory processes, and metabolic enzymes was measured by Fluidigm multiplex qPCR. This generated a gene expression profile portraying the upregulation of genes associated with energy storage but not energy mobilization. Leptin expression was increased 20-fold as adipose mass increased. Interestingly, gene transcription for the receptors of insulin signaling (IR, IRS1, ISR2) were downregulated, even when genes leading to glucose transport (GLUT4, GPR120/FFR4) were upregulated. This relationship could show a disconnect between the quenching of insulin signaling (insulin resistance), while also fueling glucose transport early in weight gain, providing a potential focus of interest for future investigation. The gene expression of transcription factors PPARG1, PPARG2 and SREBP1c were higher in ad libitum fed cats as was lipoprotein lipase, but not hormone sensitive lipase. These findings indicate an orchestrated metabolic response to accommodate for adipogenesis and maintain lipid homeostasis due to increased calories during ad libitum feeding.