Abnormal polyunsaturated lipid metabolism in the obese Zucker rat, with partial metabolic correction by γ-linolenic acid administration

Stephen D. Phinney, Anna B. Tang, Debbie C. Thurmond, Manabu T. Nakamura, Judith S. Stern

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Below-normal proportions of phospholipid (PL) arachidonic acid (20:4ω6) have been reported in serum from obese humans and in liver from obese Zucker rats. This implies an abnormality of 20:4ω6 formation from linoleic acid (18:2ω6), possibly in the Δ6 desaturase step, or alternatively an abnormality in the catabolism or distribution of arachidonate. We previously speculated that a reduced proportion of 20:4ω6 in hepatic PL could contribute to the etiology of genetic obesity. Providing 18:3ω6 would bypass Δ6 desaturase and possibly normalize hepatic PL 20:4ω6. Therefore weanling Zucker rats were given free access to a defined diet (11% of energy as soy oil) and gavaged daily with 100 μL of either black currant oil concentrate ([BCO] 8% 18:2ω6 and 70% 18:3ω6) or soy oil ([Soy] 55% 18:2ω6 and <0.1% 18:3ω6). Groups of eight lean and eight obese animals were randomized to receive Soy or BCO in a 2 × 2 design; 10 obese and 10 lean rats were fed a stock diet (nongavaged reference). All groups of lean rats had identical weight gain; food intake for Soy lean and BCO lean did not differ. The obese reference animals and Soy obese animals did not differ in weight gain. However, BCO obese animals ate less food (P < .06), gained less weight (P < .0001), and had lower percent body fat (P < .05) compared with the Soy obese animals. The fatty acid constituents from serum, liver, and adipose tissue showed marked differences between lean and obese animals. Hepatic PL 20:4ω6 was lower in Soy obese than in lean (P < .002), but was normalized by BCO gavage (diet effect, P < .007). The paucity of hepatic PL 20:4ω6 was not due to reduced desaturase activity, as the proportions of other desaturase products (20:3ω6, 20:3ω9, 20:5ω3) were significantly elevated in Soy obese rat liver and serum. Serum and hepatic cholesteryl ester 20:4ω6 levels were elevated in obese versus lean rats (P < .02 and P < .0001), indicating abnormal arachidonate distribution in the obese Zucker rat. Because BCO selectively reduced weight gain and percent body fat in obese Zucker rats, our results imply a role for abnormal ω6 fatty acid metabolism in the etiology of Zucker obesity. However, due to the potential risks of enhancing tissue 20:4ω6, great caution is advised in extrapolating our results with BCO to the treatment of obesity in humans.

Original languageEnglish (US)
Pages (from-to)1127-1140
Number of pages14
JournalMetabolism
Volume42
Issue number9
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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