Changes in fatty acids profiles after three weeks of high-fat diet feeding in obesity-prone rats

Abstract

High-fat diet (HFD) feeding is commonly used in animal models to induce obesity and metabolic diseases. However, the effect of HFD on serum fatty acid profiles remains unclear. Changes in serum fatty acid profiles due to HFD may be a factor in lipotoxicity in various organs. Historically, in vitro studies have utilized individual non-esterified fatty acids (NEFA) to study lipid exposure, potentially ignoring the importance of fatty acid combinations on cellular lipid metabolism. OBJECTIVE: To accurately characterize the proportion of circulating fatty acids entering and exiting the liver in obese-prone rats fed with HFD in both fasted and fed state. Our ultimate goal is to create a physiological relevant fatty acid mixture to investigate lipid exposure in a cell culture system. METHODS: Obesity prone rats were fed a HFD (60%kcal fat) or a control diet (10%kcal fat) for 3 weeks; liver, portal and systemic blood samples were collected. Triglycerides (TG) and NEFA in the serum, TG, diglycerides (DG) and phospholipids (PL) in the liver were extracted and analyzed using gas chromatography. RESULTS: HFD group was heavier and had bigger fat pad compared to control diet fed animals. Both systemic and portal serum TG were ̃40% lower in HFD. In contrast, liver had higher fasting TG (̃2-fold) and DG (̃1.3-fold) in the HFD group compared to control group. Total serum NEFA levels were not affected by diet in the fasted state, but increased in the HFD group compared to the control group under fed state. In the control group, monounsaturated fatty acids (MUFA) were the predominant fatty acids in serum TG, whereas polyunsaturated fatty acids (PUFA) were the dominant fatty acids in the HFD group. The elevations of PUFA were mostly attributed to the increased of n-6 PUFA, linoleic acid and arachidonic acid. Similar shift from MUFA to n-6 PUFA also occurred in the serum NEFA fraction. CONCLUSION: HFD shifted predominate fatty acids of serum TG fraction from MUFA in the control diet to n-6 PUFA. A more physiologic