Abnormal regulation of serum lipid fatty acid profiles in short gut rats fed parenteral nutrition with lipid

Abstract

Despite absence of essential fatty acid deficiency (EFAD), increases in arachidonic acid to linoleic acid ratios occur in serum phospholipid of patients treated with chronic total parenteral nutrition (TPN). The parenteral lipid component of TPN contains abundant linoleate; thus low phospholipid linoleate may reflect increased conversion to arachidonate. Arachidonic acid excess has been associated with a proinflammatory milieu through increased eicosanoid production and might contribute to the increases in inflammatory markers seen in home TPN patients. We investigated fatty acid metabolism in a rodent model of malabsorption. We hypothesized that short gut rats would metabolize parenteral lipid differently from intact rats. We performed laparotomy and 80% small bowel resection (or sham surgery) in rats. Sixteen sham and 16 short gut rats were randomly assigned to TPN with lipid or fat-free TPN. After 5 days, weight loss was similar in all groups. Analysis of serum phospholipids demonstrated that 20:3omega9 (eicosatrienoic acid) was relatively increased in fat-free TPN groups, irrespective of surgery type, as were distal very long chain omega3 class fatty acids, as anticipated. Uniquely, both nutrition (TPN/lipid v fat-free TPN) and surgery type (sham v short gut) were significant in determining arachidonic acid levels. Relatively elevated arachidonate occurred in both groups of fat-free rats, suggesting increased Delta6 and/or Delta5 desaturase activity, as expected. In contrast, giving TPN/lipid lowered arachidonate (suggesting appropriately downregulated desaturases) in sham animals, but not in short gut animals. Ratios of arachidonic and di-homo-gamma-linolenic to linoleic acids further suggested increased turnover of precursor omega6 to arachidonic acid in short gut rats given lipid compared with the other groups. These preliminary data show that intravenous (IV) lipid gave rise to serum lipid fatty acid profiles that differed in short gut and sham rats. The short gut rat may have a heightened hepatic desaturase activity, inappropriate for the quantity of linoleic acid provided parenterally. Therefore, the short gut rat is an appropriate model to study further arachidonic acid excess in home TPN patients.