Evaluation of Compounds that Inhibit Fatty Acid Uptake in Mice

Lipotoxicity is characterized by apoptosis due to the toxic spillover of fatty acids from adipocytes into non-adipose tissue. Adipocytes function to store fat and then release free fatty acids during fasting and starvation. In obesity, however, storage capacity in adipocytes becomes limiting and circulating triglycerides and free fatty acids are elevated, which can lead to accumulation in non-adipose tissue. This can result in dysfunction, especially in the liver, muscle and pancreas. The purpose of this research is to measure the degree of fatty acid uptake inhibition in mouse models by two long-chain fatty acid transport protein inhibitors, designated lipofermata and grassofermata in previous work. 13C18-labeled oleic acid provided in flaxseed oil was delivered to mice by gavage following administration of compound or vehicle in flaxseed oil and the animals were sacrificed and blood collected by cardiac puncture. Plasma, tissue, and fecal levels of 13C18-oleate were assessed by gas chromatography/mass s...