Carnitine and Altered Lipid Metabolism in Iron-Deficient Rats Pre- and Postweaning (Ketogenesis)

147 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1986.Triglyceride-rich liver and hypertriglyceridemia occur in offspring of iron-deficient rats. Mechansims responsible for the altered lipid metabolism have not been fully determined. The hypothesis proposed in this thesis was that severe iron deficiency in the suckling rat impairs the iron-dependent synthesis of carnitine, thereby shunting long-chain fatty acids away from oxidation and ketogenesis into triglyceride synthesis increasing triglyceride levels in serum and liver. The rationale for carnitine involvement is based on two facts: (1) carnitine synthesis in vitro requires ferrous iron; and (2) carnitine is required to transport long-chain fatty acids into mitochondria for oxidation and ketone production. Ketone bodies are a major energy source for suckling animals.Sprague-Dawley rat pups were made iron-adequate (+Fe) or iron deficient (-Fe) by feeding dams either 250 ppm Fe or 6 ppm Fe throughout gestation and lactation. The first study indicated lower levels of carnitine and higher triglyceride concentrations in liver of -Fe pups on day 16. Milk of -Fe dams contained 63% less Fe than control milk but had similar levels of carnitine and amino acids. In the second study, ketogenesis was lower in liver mitochondria from -Fe pups in response to carnitine added in vitro than in +Fe mitochondria on day 16. This difference in response indicated a factor other than carnitine was depressing ketogenesis in -Fe pups. Supplementation for eight days with L-carnitine or ferrous sulfate during suckling restored ketogenic activity in -Fe mitochondria to +Fe levels. Liver triglyceride was reduced more by Fe supplementation than by L-carnitine, however. Postweaning repletion with dietary D, L-carnitine decreased liver triglycerides in females below control levels by four weeks. -Fe females not receiving dietary Fe or carnitine for four weeks had normal levels of triglyceride in liver. Repletion with Fe for two or four weeks reduced triglyceride in liver and skeletal muscle of animals at both time points.Results indicate carnitine is more important during suckling than postweaning. Carnitine or Fe corrected ketogenesis in -Fe pups, but Fe decreased liver triglycerides more than carnitine. Postweaning carnitine had little effect on lipid metabolism compared to dietary Fe.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD