OBJECTIVE The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones. DESIGN Venous cord blood samples were obtained from 59 full-term healthy newborns (36 males and 23 females, gestational age 37·0 -41·4 weeks, birth weight 2,146 -4,326 g, birth length 44·0 -54·5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3 -7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined. MEASUREMENTS The adiponectin concentration was determined by enzyme-linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF-1 concentrations were determined by immunoradiometric assays. RESULTS The plasma adiponectin concentrations in cord blood ranged from 6·0 to 55·8 µ µ µ µ g/ml (median 22·4 µ µ µ µ g /ml), which were much higher than those in normal-weight adults ( P < 0·0001). In contrast to the findings in adults, these values were positively correlated with birth weight ( r = 0·43, P = 0·0005), body mass index ( r = 0·44, P = 0·0005), birth weight / birth length ratio ( r = 0·46, P = 0·0002) and the leptin concentrations ( r = 0·39, P = 0·004). When the effects of fat massrelated anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations ( r = − − − − 0·35, P = 0·01). There was no significant gender difference in adiponectin concentrations among newborns. The

Sphingolipid activator proteins (saposins A, B, C and D) are small homologous glycoproteins derived from a common precursor protein (prosaposin) encoded by a single gene. They are required for in vivo degradation of sphingolipids with short carbohydrate chains. Six cysteines and one glycosylation site are strictly conserved in all four saposins. Total deficiency of all saposins and specific deficiency of saposin B or C are known among human patients. A mouse model of total saposin deficiency closely mimics the human disease. However, no specific saposin A or D deficiency is known. We introduced an amino acid substitution (C106F) into the saposin A domain by the Cre/loxP system which eliminated one of the three conserved disulfide bonds. Saposin A(-/-) mice developed slowly progressive hind leg paralysis with clinical onset at approximately 2.5 months and survival up to 5 months. Tremors and shaking, prominent in other myelin mutants, were not obvious until the terminal stage. Pathology and analytical biochemistry were qualitatively identical to, but generally much milder than, that seen in the typical infantile globoid cell leukodystrophy (GLD) in man (Krabbe disease) and in several other mammalian species, due to genetic deficiency of lysosomal galactosylceramidase (GALC) (EC 3.2.1.46). Thus, saposin A is indispensable for in vivo degradation of galactosylceramide by GALC. It should now be recognized that, in addition to GALC deficiency, genetic saposin A deficiency could also cause chronic GLD. Genetic saposin A deficiency might be anticipated among human patients with undiagnosed late-onset chronic leukodystrophy without GALC deficiency.

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To investigate the relationship between ghrelin and both fetal and neonatal growth parameters and energy balance, we measured plasma ghrelin concentrations in 54 cord blood samples (male, n = 34; female, n = 20; gestational age, 37.0-41.6 wk; birth weight, 2206-4326 g) and 47 neonatal blood samples (male, n = 27; female, n = 20; postnatal d 3-8). The plasma ghrelin concentrations in cord blood ranged from 110.6-446.1 pmol/liter (median, 206.7 pmol/liter), which were equal to or higher than those in normal weight adults. These values were inversely correlated with birth weight (r = -0.40; P = 0.002), birth length (r = -0.36; P = 0.007), placental weight (r = -0.35; P = 0.01), and IGF-I concentration (r = -0.49; P = 0.0002), but were not significantly correlated with the GH concentration (r = 0.22; P = 0.12). The ghrelin concentrations in small for gestational age newborn were significantly higher than those in appropriate for gestational age newborns (P = 0.0008). The ghrelin concentrations in the vein were significantly higher than those in the artery in 8 cord blood samples (P = 0.01), which suggests that the placenta is an important source of fetal ghrelin. In neonates, the ghrelin concentrations ranged from 133.0-481.7 pmol/liter (median, 268.3 pmol/liter), which were significantly higher than those in cord blood (P < 0.0001). These results suggest that ghrelin may contribute to fetal and neonatal growth.

The sphingolipid activator proteins (saposins A, B, C and D) are small homologous glycoproteins that are encoded by a single gene in tandem within a large precursor protein (prosaposin) and are required for in vivo degradation of some sphingolipids with relatively short carbohydrate chains. Human patients with prosaposin or specific saposin B or C deficiency are known, and prosaposin- and saposin A-deficient mouse lines have been generated. Experimental evidence suggests that saposin D may be a lysosomal acid ceramidase activator. However, no specific saposin D deficiency state is known in any mammalian species. We have generated a specific saposin D(-/-) mouse by introducing a mutation (C509S) into the saposin D domain of the mouse prosaposin gene. Saposin D(-/-) mice developed progressive polyuria at around 2 months and ataxia at around 4 months. Pathologically, the kidney of saposin D(-/-) mice showed renal tubular degeneration and eventual hydronephrosis. In the nervous system, progressive and selective loss of the cerebellar Purkinje cells in a striped pattern was conspicuous, and almost all Purkinje cells disappeared by 12 months. Biochemically, ceramides, particularly those containing hydroxy fatty acids accumulated in the kidney and the brain, most prominently in the cerebellum. These results not only indicate the role of saposin D in in vivo ceramide metabolism, but also suggest possible cytotoxicity of ceramide underlying the cerebellar Purkinje cell and renal tubular cell degeneration.