10-Day Hyperlipidemic Clamp in Cats: Effects on Insulin Sensitivity, Inflammation, and Glucose Metabolism-related Genes

Abstract

Obesity and hyperlipidemia are associated with impaired insulin sensitivity in human type 2 diabetes mellitus, possibly due to activation of a mild inflammatory response. Because obesity-induced insulin resistance predisposes cats to diabetes and because hyperlipidemia is a frequent concurrent finding, excess lipids may also impair insulin sensitivity in cats. Healthy cats (n=6) were infused with lipids (Lipovenoes^R 10%) for 10 days to clamp blood triglycerides at the approximate concentration of untreated feline diabetes (3–7 mmol/l). Controls received saline (n=5). On day 10, plasma adiponectin and proinflammatory markers were measured. Whole-body insulin sensitivity was calculated following an intravenous glucose tolerance test. Tissue mRNAs of glucose metabolism-related genes were quantified in subcutaneous and visceral fat, liver, and skeletal muscles. Accumulation of lipids was assessed in liver. At the termination of infusion, whole-body insulin sensitivity did not differ between groups. Compared to saline, cats infused with lipids had 50% higher plasma adiponectin and 2–3 times higher α₁-acid glycoprotein and monocyte chemoattractant protein-1. Unexpectedly, lipid-infused cats had increased glucose transporter-4 (GLUT4) mRNA in the visceral fat, and increased peroxisome proliferative activated receptor-γ2 (PPARγ2) in subcutaneous fat; adiponectin expression was not affected in any tissue. Lipid-infused cats developed hepatic steatosis. Although hyperlipidemia induced systemic inflammation, whole-body insulin sensitivity was not impaired after 10 day infusion. Increased circulating adiponectin may have contributed to prevent insulin resistance, possibly by increasing GLUT4 and PPARγ2 transcripts in fat depots.

feline - lipid infusion - adiponectin - inflammation

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