Metabolic Adaptation in Developing Lung

Abstract

incorporation into lipids was concentrations were chosen because they gave optimal rates of greatest at 18 to 19 days of fetal development, at which time the oxidation. lung content of nonesterified fatty acids was highest.The flasks were fitted with rubber caps and polypropylene center wells and incubated in a shaking water bath at 37OC for Speculation one hr. Under these conditions, production of I4COz from labeled substrates was linear for at least 2 hr. At the end of the incubation, Tbe changes substrate oxidation and Utili~atioll observed in 0.3 ml of hymine hydroxide was injected through the serum cap developing lung probably reflect ch~nges in the avdabmty of into the center well to trap evolved "COz, the reaction was substrates and requirements for precursors to support functional terminated, and COz was released by the injection of 1 ml of 2m and mor~hologic differentiation of lung-Changes in cpochrome trichloroacetic acid through the cap down the side of the flask into oxidase activity in the postnatal period may reflect differential the incubation medium. After 45 min of further incubation, the lung growth.contents of the center well were transferred to counting vials containing 10 ml of Emnofluor (33), and radioactivity was measured in a liquid scintillation counter (35). Blanks were incubated The developing lung requires energy for growth and maturation along with the samples and treated in the same way. Standards as well as for the synthesis of surface active phospholipids which were prepared containing 100 pl of the incubation mix and counted maintain postnatal alveolar stability. Although there is consider-in 10 ml of Aquasol (33). The flasks or medium were not oxygenable information concerning glucose and fatty acid metabolism in ated because this did not affect the rate of substrate oxidation to adult lung, little is known about fatty acid and glucose oxidation COz. in the developing lung. Early work by Geyer et al. (8) showed that For measurement of fatty acid incorporation into lipid, slices adult rat lung slices oxidized radiolabeled triolein and octanoic (50 to 200 mg wet wt) were incubated at the same substrate acid to 14c02. Subsequent studies by Felts (7) using adult rat lung concentrations in 2 ml of medium. The reaction was terminated slices demonstrated oxidation of [1-"clpalmitate to I4Coz. This by transfer of the flask to ice. The medium then was aspirated, work was confirmed by Salisbury-Murphy et al. (18) in rabbit and and the tissue was washed with ice-cold 0.Wo saline until the wash later by Wang and Meng (24) in the rat. Shaw and Rhoades (19) was free of radioactivity (about five washes). The slices were then in the perfused rat lung reported that high concentrations of removed with forceps to a Dounce homogenizer and homogenized palmitate (1.8 mM) inhibited glucose oxidation to COz, suggesting in 1.6 ml of cold 0.9% saline. The homogenate was transferred to that under some conditions palmitate may be a preferred substrate. a stoppered centrifuge tube, 6 ml of chloroform:methan...

Fatty Acid Oxidation by Developing Rat Kidney

“…The capacity of kidney to oxidize palmitate increases after birth, the highest values being observed on day 5. A similar developmental pattern has been demonstrated for long chain fatty acids oxidation with fetal heart [11,15], liver [1,8], brain [12] and lung [13]. In fetal heart the first step of fatty acids activation appears to be rate-limiting for palmitate oxidation [2].…”

“…In fetal liver both palmityl-CoA synthetase [10] and palmityl-carnityl transferase [1,8] activities have been found to increase sharply immediately after birth, concomitantly with palmitate oxidation into CO2. Lung palmi tate oxidation into CO2 shows a striking postnatal increase [ 13] parallel to the increase in palmityl-carnityl transferase and cyto chrome oxydase. In our experiments the rise of palmitate concentration in the medium (1.5 instead of 0.5 mM ) increases the palmi tate uptake by fetal kidney slices whereas it does not change palmitate oxidation.…”

Integrated Substrate Utilization by Perinatal Lung

“…Since the tissue slice has been widely used to study hormonehubstrate influences on overall metabolic activity in the fetal lung and is highly reproducible [ 10,13,[17][18][19] , this preparation was employed to assess relative utilization of exogenously supplied substrates at different times in perinatal lung development. Some damage is sustained by the tissue during the slicing procedure and thus rates are probably somewhat altered from that of the tissue in vivo but serve as a good approximation.…”

Fatty acid oxidation and ketogenesis during development

“…Similarly, compared to adults, the rate of palmitate oxidation is reduced in skeletal muscle homogenates (Glatz and Veerkamp, 1982 ;Carroll et al, 1983 ;Wolfe, Maxwell and Nelson, 1978 ;Mac Larty et al, 1984) and in kidney slices (Wolfe, Maxwell and Nelson, 1978 ;Freund, Sedraoui and Geloso, 1984), lung (Warshaw, Terry and Ranis, 1980) and small intestine (Warshaw, 1974) of fetal rats and pigs. As the rate of oxidation of octanoate, octanoylcarnitine or palmitoylcarnitine is similar in the heart of fetal, newborn and adult pigs and calves (Werner et al, 1983a, b ;Warshaw and Terry, 1970), it has been suggested that the reduced capacity of the fetal tissues to oxidize long-chain fatty acids could result from the low activity of carnitine acyltransferase I (Warshaw, 1972 ;Carroll et al, 1983 ;Delaval et al, 1984).…”

“…A rise in this activity occurs immediately after birth in the heart (Wittels and Bressler, 1965 ;Warshaw, 1972 ;Lockwood and Bailey, 1970 ;Barrie and Harris, 1977), skeletal muscle (Carroll et al, 1983), lung (Warshaw, Terry and Ranis, 1980) and kidney (Delaval et al, 1984) of rats and remains elevated throughout the suckling period. However, CAT activity does not change with age in the heart, leg muscles and kidney of pigs, although palmitate oxidation increases 2 to 3-fold (Wolfe, Maxwell and Nelson, 1978).…”