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Enhanced Fatty Acid Synthesis in Hyperinsulinemic Rat Fetuses^1,2,

Department of Pediatrics, Women and Infants Hospital of Rhode Island; Brown University Program in Medicine, Providence, RI 02908

The relationship between insulin-induced macrosomia and fetal fatty acid synthesis in nine pregnant rats was evaluated using the tritiated water technique. On days 19 and 21 of gestation, alternate fetuses were injected with equal volumes of either saline or insulin (5 units). Fetal hyperinsulinemia resulted in a significant increase in fetal weight and selected organ weights (liver, lung and carcass). Significant increases in fatty acid synthesis in fetal liver and carcass were observed on day 22 of gestation. In liver tissue, increased fatty acid synthesis occurred as evidenced by increased tritium incorporation into fatty acids in insulin-injected fetuses, 690 ± 124 cpm/liver, compared to controls, 400 ± 92 cpm/liver (P < 0.001); higher fatty acid content, 16.0 ± 1.3 µmol/liver in hyperinsulinemic fetuses, compared to 12.3 ± 1.0 µmol/liver in controls (P < 0.005); and a higher fatty acid specific activity, (expressed as tritium counts per minute per micromole fatty acid) 44.5 ± 8.6 cpm/µmol fatty acid, compared to control levels of 33.0 ± 7.5 (P < 0.005). Analysis of carcass revealed higher tritium incorporation into fatty acids in insulin-injected fetuses, as compared to controls, 2136 ± 172 versus 1139 ± 122 cpm/carcass (P < 0.001); higher fatty acid content, 68.1 ± 7.3 versus 59.4 ± 6.4 µmol/carcass (P < 0.05); and fatty acid specific activity, 34.5 ± 4.8 versus 21.9 ± 4.4 cpm/µmol (P < 0.001), respectively. There were no differences in the incorporation of tritium into fatty acids or fatty acid content in the lung, brain and placenta in the insulin-treated fetus as compared to control littermates. The data indicate that insulin is a lipogenic hormone for the fetus and that this model can be used as a means of studying effects of insulin on fat metabolism in fetal life.

KEY WORDS: • hyperinsulinemia • fatty acid synthesis • macrosomia • fetal "overnutrition"

¹ Supported in part by Diabetes Training Grant #AM-07187 of the National Institute of Arthritis and Metabolism and Major Research Program #HD-11343 of the National Institute of Child Health and Human Development, Bethesda, Maryland.

² Presented in part at the Society for Pediatric Research Meeting Vileisis, R. A. & Oh. W. (1982) Enhanced fatty acid synthesis in hyperinsulinemic rat fetuses. Pediatr. Res. 16(2), 266A (abs.).

³ Current address is Duke University Medical Center, Box 3967, Division of Perinatal Medicine, Durham, NC 27710.

⁴ To whom reprint requests should be sent.

Manuscript received 29 June 1982.