Hepatic fatty acid degradation during development of the rat.

It is now well established that major changes in hepatic fatty acid degradation occur at birth and at weaning. Thus the rate of oxidation of [14C]palmitate by liver preparations increases rapidly after birth and decreases on weaning (Lockwood & Bailey, 1970; Bailey & Lockwood, 1973). Similar changes are observed with regard to theconcentration of ketone bodies in the blood (Lockwood &Bailey, 1971), the rate of hepatic ketone-body formation and the activities of the enzymes involved in hepatic ketogenesis (Lockwood & Bailey, 1970, 1971 ; Hipolito-Reis et al., 1974). Somewhat reciprocal changes occur in hepatic lipogenesis and the activities of enzymes associated with lipogenesis (Taylor et al., 1967; Ballard & Hanson, 1967; Lockwood et al., 1970). Such changes can be correlated with the dietary changes that occur at birth and at weaning (Bailey & Lockwood, 1973), thus suggesting that nutritional factors are involved. However, it has been shown that considerable changes in hepatic lipid metabolism also occur during the midsuckling period, at a time when no major alterations in the composition of the milk diet are to be expected. Thus the developmental pattern for acylcarnitine oxidation shows a minimum at about 9 days of age (Foster &Bailey, 1976~). Similar developmental changes have been demonstrated for palmitate oxidation and palmitate conversion into ketone bodies by liver mitochondria, the concentration of ketone bodies and triglycerides in the blood (Foster & Bailey, 1976a), the activities of many of the hepatic mitochondrial enzymes involved in fatty acid oxidation (Foster & Bailey, 19766), and the activities of the enzymes of hepatic mitochondrial ketogenesis. In contrast, some enzymes involved in hepatic lipogenesis exhibit a small peak of activity during the mid-suckling period (Webb & Bailey, 1975). Experiments have been carried out to try to discover dietary and hormonal factors involved in the observed changes in hepatic fatty acid degradation. The particular hormones used in the present study (growth hormone, thyroid-stimulating hormone, adrenocorticotrophic hormone, glucagon, corticosterone, thyroxine and adrenaline) were chosen because they have all been shown to affect lipid metabolism in the adult rat. Injection of corticosterone into foetuses in utero caused a small increase in the capacity for hepatic fatty acid oxidation (as measured by the mitochondrial palmityolcarnitineoxidation rate). Both thyroxine and corticosterone, when injected on day 6 after birth, increased the capacity for hepatic fatty acid oxidation 1 day later, and injection on days 11 and 12 increased 3-hydroxyacyl-CoA dehydrogenase activity on days 13 and 14. Corticosterone injection on day 6 resulted in increased blood ketone-body concentration on day 7, whereas thyroxine injections did not. Injection of thyroid-stimulating hormone on day 6 had the same effects as thyroxine injection. Other hormones were without effect. Thus it seems likely that thyroxine and corticosterone are involved in the control of the capacity for hepatic fatty acid oxidation, blood ketone-body concentrations and 3-hydroxyacyl-CoA dehydrogenase activity. The developmental patterns of the serum concentrations of free and total thyroxine are paralleled by that for the activity of the dehydrogenase. However, it is difficult to explain the developmental pattern of the capacity for fatty acid oxidation simply as a reflexion of either the serum thyroxine or plasma corticosterone concentrations since serum thyroxine is present at low concentration in the few days after birth (when there is a peak of fatty acid oxidation), and the