i(3)so3-galactosylceramide and Body-Weight

Topics: Animals; Body Weight; Brain; Disease Models, Animal; DNA; Dopamine; Female; Gangliosides; Gestational Age; Humans; Intelligence; Myelin Sheath; Neuroglia; Neurons; Norepinephrine; Nutrition Disorders; Organ Size; Pregnancy; Proteins; Rats; Sulfoglycosphingolipids; Thyroid Gland; Time Factors

The interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated. We previously reported that myelin-enriched sulfatide loss leads to CNS neuroinflammation and cognitive decline. In this study, we further investigated the impact of CNS sulfatide deficiency on peripheral metabolism while considering sex- and age-specific effects. We found that female sulfatide-deficient mice gained significantly more body weight, exhibited higher basal glucose levels, and were glucose-intolerant during glucose-tolerance test (GTT) compared to age-matched controls under a normal diet, whereas male sulfatide-deficient mice only displayed glucose intolerance at a much older age compared to female sulfatide-deficient mice. Mechanistically, we found that increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypothalamus, in a sex-specific manner. Our results suggest that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food intake.

Topics: Aging; Animals; Body Weight; Central Nervous System; Female; Male; Mice; Mice, Knockout; Neuroinflammatory Diseases; Obesity; Sulfoglycosphingolipids

Lead poisoning is known to cause myelin defects. Galactolipids are the major lipid components of myelin and myelin-competent oligodendrocytes. The present study examines the cellular activity of enzymes involved in the galactolipid pathway, tissue concentrations of galactolipids, and the cellular activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) in rat pups exposed to lead in utero and subsequently through maternal milk from exposed mothers and in drinking water following weaning. Pups from control and lead-treated groups (500 or 2000 ppm lead in the drinking water) were euthanized by decapitation on postnatal day 7, 14, 21, 35, or 56. Lead decreased levels of galactolipids and the oligodendrocyte marker CNPase in the brain to a similar degree. The ratios of galactocerebrosides/sulfatides and nonhydroxy fatty acid/hydroxy fatty acid forms of the galactolipids were not altered by lead treatment. In contrast, the activities of the galactolipid metabolic enzymes were reduced to a degree significantly greater than that of CNPase or galactolipids. These results are consistent with previously obtained data indicating that in vitro cultured oligodendroglial progenitor cells are a target for Pb toxicity. Chronic Pb exposure may impact on brain development by impairing timely myelin production due to perturbation of the early developmental commitment of oligodendroglial progenitors. It is further suggested that perturbation of the galactolipid pathway during the developmental maturation of oligodendrocytes may represent a contributing mechanism for Pb-induced neurotoxicity.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Body Weight; Brain; Female; Galactolipids; Galactosylceramides; Galactosyltransferases; Glycolipids; Lactation; Lead; Lead Poisoning, Nervous System; Mice; Mice, Knockout; Myelin Sheath; N-Acylsphingosine Galactosyltransferase; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Long-Evans; Sulfoglycosphingolipids; Sulfotransferases

Changes in serum lipids and lipoproteins and progression of atherosclerosis with age were examined in Watanabe heritable hyperlipidemic (WHHL) rabbits with or without treatment with sulfatide. The injection of sulfatide solution caused a reduction of serum triacylglycerols for five months including the period of treatment, but afterwards, failed to lower the level of total cholesterol, triacylglycerols and phospholipids, and to suppress the progression of atherosclerosis. Concentrations of LDL as a major serum lipoprotein in WHHL rabbits with or without the treatment with sulfatide were found to be about 64-fold those of normal rabbits by immunological assay using anti-LDL antiserum, whereas the contents of total cholesterol, triacylglycerols, and phospholipids in WHHL rabbit sera were found to be about 10-fold those of normal rabbits. All WHHL rabbits with or without the treatment with sulfatide contained very small amounts of HDL. Types of apoproteins of isolated LDL and VLDL fractions suggested that the former seemed to be derived from VLDL remnant, and the latter to be derived from chylomicron remnant. It was noted that all WHHL rabbit sera had a significant increased amount of lysophosphatidylcholine, and that the fatty acid composition of total serum lipids had almost no change except for slight decrease in arachidonic acid with age. Pathological examination showed that severe atherosclerotic lesions were not so different between WHHL rabbits with or without treatment with sulfatide at age over 22 months.

Topics: Aging; Animals; Aorta; Arteriosclerosis; Body Weight; Cholesterol; Hyperlipidemias; Lipoproteins; Rabbits; Sulfoglycosphingolipids

Parameters of brain development were studied in near term guinea-pigs in relation to fetal weight and maternal glucose tolerance during normal gestation. Seven litters (22 fetuses) were studied. Fetal weight ranged from 43 to 94 g (119% variability) and the maternal glucose index (sum of the 7 serum glucose levels during the oral glucose tolerance tests) from 921 to 1,528 mg/dl (66% variability). The weights of the cerebrum and cerebellum were less affected by changes of fetal weight compared to other fetal organs. Significant correlations were observed between the maternal glucose index and brain cell number (DNA) and myelination (cerebroside-sulfatide). These variables did not correlate with fetal weight. Liver weight (% fetal weight) and cell number also correlated with the maternal glucose index. It is speculated that the amount of glucose available to the brain could be responsible for the relative protection of the brain to fetal malnutrition and also for the link between maternal glucose index and parameters of fetal brain development.

Topics: Animals; Blood Glucose; Body Weight; Brain; Cerebrosides; DNA; Embryonic and Fetal Development; Female; Gestational Age; Glucose Tolerance Test; Guinea Pigs; Maternal-Fetal Exchange; Organ Size; Pregnancy; Proteins; Sulfoglycosphingolipids

Developmental effects of a single hydrocortisone (HC) injection (80 micrograms/g on day 2 postnatal) were compared in two closely related species, meadow voles (Microtus pennsylvanicus) and pine voles (M. pinetorum). Effects of hormone administration were assessed in terms of the development of swimming behavior (head/nose position and front paw movement), alterations in social interactions (spatial location with respect to a stimulus animal), and by changes in somatic and brain growth. Although adult patterns of swimming behavior were found to be quantitatively different in meadow and pine voles, normal maturation in both species involved a progressive elevation of head/nose position along with a gradual inhibition of front paw movement. Compared with saline controls, HC-treated meadow voles showed an accelerated attainment of their adult pattern, whereas hormone-treated pine voles displayed a retardation in their swimming development. HC administration similarly led to increased body weights in developing meadow voles but decreased body weights in young pine voles. There was a tendency for hormone-treated meadow voles to spend more time near a stimulus animal than their control counterparts, whereas the opposite was observed for pine voles. In both species, the HC group displayed decreased cerebral and cerebellar weights in adulthood, whereas other organs were generally unaffected by hormone administration. Neurochemical analyses revealed no treatment effects or treatment by species interactions with respect to cerebral DNA levels. On the other hand, treated meadow voles but not pine voles showed an elevated concentration of sulfatide, a myelin-related lipid. These results are the first to demonstrate divergent behavioral and neurochemical effects of early glucocorticoid administration in closely related species studied under the same conditions. Furthermore, in accordance with earlier experiments on rats, swimming behavior was shown to be a useful measure for assessing changes in neuromuscular maturation.

Topics: Animals; Arvicolinae; Behavior, Animal; Body Weight; Brain; DNA; Female; Humans; Hydrocortisone; Infant, Newborn; Male; Organ Size; Personal Space; Sulfoglycosphingolipids; Swimming

Snell dwarf mice (dw/dw) and normal mice (+/?) were injected with thyroxine (T4) (1 microgram/animal, four injections) and growth hormone (GH) (20 micrograms/animal, four injections) from the 5th to the 15th day of life. In the untreated dw/dw mouse brain, the specific activities of UDP-galactose:ceramide galactosyltransferase (CGalT), PAPS:cerebroside sulfotransferase (CST), and 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNP) were decreased by 28, 25, and 37%, respectively, compared with the control untreated +/? mice. The major effect of T4 was an increase of the brain CNP in the +/? mice (+40%) and dw/dw mice (+111%). The treatment with T4 also brought to normal the level of CGalT in dw/dw brain; a somewhat less marked effect on CST was observed. The treatment with GH had a great stimulatory effect on CNP: the specific activity of this enzyme increased by 40 and 69% in +/? and dw/dw mouse brain, respectively. On the contrary, no effect of GH on the CGalT activity was observed in this study. Our results suggest that T4 and GH may have both independent and complementary actions on the myelin-associated enzymes during the early postnatal period of brain development.

Topics: Aging; Animals; Animals, Newborn; Body Weight; Brain; Cerebrosides; Growth Hormone; Mice; Mice, Mutant Strains; Organ Size; Sulfoglycosphingolipids; Thyroxine

The action of neonatal hypothyroidism and early undernutrition on the lipid and protein composition, as well as, on the activity of 2'3' cyclic nucleotide 3' phosphohydrolase was studied in different subcellular fractions isolated from 20 day old hypothyroid and undernourished rats. Based on protein content, a marked decrease (70%) in the recovery of myelin was observed in both experimental conditions. The lipid composition of myelin in both groups was, however, different; while cholesterol, total phospholipids, and total galactolipids decreased in a similar fashion in the two situations; sulfatides and plasmalogens were much more affected in hypothyroid rats.

Topics: Animals; Animals, Newborn; Body Weight; Brain; Female; Gangliosides; Hypothyroidism; Lipid Metabolism; Male; Nerve Tissue Proteins; Nutrition Disorders; Organ Size; Phospholipids; Rats; Sulfoglycosphingolipids

Neonatal hypothyroidism reduced the concentration of sulfatide in myelin and synaptosomes isolated from brains of 20-21 day old rats. The in vivo incorporation of 35SO4 into sulfatide of myelin, microsomal, animals, as was the incorporation of the isotope into non-lipid sulfate (sulfated glycoproteins and mucopolysaccarides) of microsomal and synaptosomal fractions. In contrast, when animals were made hypothyroid at one month of age, no depletion of brain sulfatide or alteration of incorporation of 35SO4 into sulfatide was found, although incorporation of the isotope into non-lipid sulfate of myelin, mitochondria and synaptosomes was increased by this treatment. These results indicate that the metabolism of sulfatide and non-lipid sulfate of brain membranes is much more susceptible to alteration by hypothyroidism in neonatal than may alter the metabolims of sulfatide and non-lipid sulfate in neuronal as well as myelin membranes.

Topics: Aging; Animals; Animals, Newborn; Body Weight; Brain; Hypothyroidism; Male; Organ Size; Rats; Subcellular Fractions; Sulfates; Sulfoglycosphingolipids

Isolated terminal colon strips obtained from rats, made hypothyroid by methimazole treatment, were almost completely insensitive to the contractile effects of morphine as compared to strips from control animals. This low morphine sensitivity was accompanied by a significant (40%) reduction in the tissue sulfatide content. Although colon strips from hypothyroid rats showed a reduction of the contractile effects of acetylcholine, the decrease was considerably less than that noted for morphine. The addition of 6.6 X 10(-5) M tri-iodothyronine to colons from hypothyroid rats largely restored the tissue sensitivity to morphine. These results suggest that sulfatides could be linked to the in vitro effects of morphine in the colon.

Topics: Acetylcholine; Animals; Body Weight; Colon; Hypothyroidism; In Vitro Techniques; Male; Methimazole; Morphine; Muscle Contraction; Muscle, Smooth; Rats; Sulfoglycosphingolipids

Topics: Animals; Body Weight; Brain; Brain Chemistry; Bread; Caseins; Cholesterol; Diet; Female; Food, Fortified; Gangliosides; Lactation; Lipids; Lysine; Organ Size; Phospholipids; Pregnancy; Rats; Sulfoglycosphingolipids; Threonine

Topics: Animals; Animals, Newborn; Body Weight; Brain; Brain Chemistry; Cerebrosides; Cholesterol; Glycolipids; Lead; Lead Poisoning; Lipids; Myelin Sheath; Organ Size; Organometallic Compounds; Phospholipids; Rats; Sulfoglycosphingolipids

Pyridoxine deficiency produced in rats during the period of development of the central nervous system resulted in a decreased incorporation of (1-14C) acetate into total lipid extracts of brain. It also resulted in a uniform decrease in the incorporation of the labeled precursor into the cholesterol, glycolipid and phospholipid fractions of brain. The specific radioactivity of purified cerebrosides and sulfatides was decreased by 78% in pyridoxine-deficient rats with respect to controls. The decreased incorporation of labeled precursor in the deficient rats was not due to the labeled precursor, since the specific radioactivity of brain acetate and the brain concentrations of acetyl coenzyme A and acetate were similar in both deficient and control rats. The results indicate that in pyridoxine deficiency established in the young rat there is an impaired formation of myelin.

Topics: Acetates; Acetyl Coenzyme A; Animals; Body Weight; Brain; Cerebrosides; Cholesterol; Glycolipids; Lipid Metabolism; Organ Size; Phospholipids; Rats; Sulfoglycosphingolipids; Vitamin B 6 Deficiency

Topics: Body Height; Body Water; Body Weight; Brain; Cephalometry; Cerebrosides; Cholesterol; DNA; Female; Gangliosides; Guatemala; Humans; Infant; Infant Nutrition Disorders; Kwashiorkor; Male; Phospholipids; Protein-Energy Malnutrition; Proteins; Sulfoglycosphingolipids

Topics: Body Weight; Brain; Brain Chemistry; Chromatography; Female; Gestational Age; Glycolipids; Humans; Infant, Newborn; Male; Organ Size; Sphingolipids; Sphingomyelins; Sulfoglycosphingolipids

Topics: Animals; Animals, Newborn; Body Weight; Brain; Cerebrosides; Cholesterol; Chromatography, Thin Layer; DNA; Lipid Metabolism; Male; Mice; Myelin Sheath; Nerve Fibers, Myelinated; Nerve Tissue Proteins; Neuroglia; Organ Size; Phospholipids; Plasma Cells; RNA; Sulfoglycosphingolipids

Topics: Animals; Body Weight; Brain; Chromosome Mapping; Crossing Over, Genetic; Genes; Mice; Mutation; Organ Size; Sulfoglycosphingolipids; Sulfur Isotopes

Topics: Animals; Animals, Newborn; Body Weight; Brain; Brain Chemistry; Carbon Radioisotopes; Cerebrosides; Chromatography, Thin Layer; Fatty Acids; Galactose; Glycolipids; Hypothyroidism; Lipids; Methimazole; Organ Size; Rats; Sphingomyelins; Sulfoglycosphingolipids; Uridine Diphosphate Sugars

Topics: Animals; Body Weight; Brain; Brain Chemistry; Brain Stem; Cerebellum; Cerebrosides; Cholesterol; DNA; Female; Gestational Age; Kinetics; Nerve Tissue Proteins; Organ Size; Rabbits; RNA; Sulfoglycosphingolipids; Time Factors

Topics: Amino Acids; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Body Weight; Brain; Carbon Isotopes; Cerebrosides; Cystathionine; Female; Gangliosides; Lipid Metabolism; Organ Size; Phospholipids; Plasmalogens; Pregnancy; Pyridoxine; Rats; Sphingolipids; Sphingomyelins; Sulfoglycosphingolipids; Tyrosine; Tyrosine Decarboxylase; Vitamin B 6 Deficiency

Topics: Animals; Body Weight; Brain Chemistry; Cerebrosides; Cholesterol; Chromatography, Gas; Encephalomyelitis, Autoimmune, Experimental; Esters; Gangliosides; Lipids; Nerve Tissue Proteins; Phospholipids; Rats; Spinal Cord; Sulfoglycosphingolipids

Topics: 17-alpha-Hydroxypregnenolone; 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Glands; Animals; Body Weight; Chemotherapy, Cancer, Regional Perfusion; Dehydroepiandrosterone; Glucuronates; Guinea Pigs; Half-Life; Hydrocortisone; Kidney; Liver; Liver Circulation; Mononuclear Phagocyte System; Pregnenolone; Progesterone; Sulfates; Sulfoglycosphingolipids; Tritium

Topics: Aging; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Brain; Cerebrosides; Cholesterol; Chromatography; Chromatography, Gas; Chromatography, Thin Layer; Diet; Fatty Acids; Fatty Acids, Essential; Food Deprivation; Glycolipids; Infant Nutrition Disorders; Lipoproteins; Myelin Sheath; Nerve Tissue Proteins; Organ Size; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylinositols; Phospholipids; Rats; Sphingomyelins; Sulfoglycosphingolipids

Myelin was isolated from the brains of "quaking" and littermate control animals and its composition was determined. The brains of quaking animals contained approximately one-fourth as much myelin as the control animals. There were qualitative as well as quantitative differences between the myelin from the two groups. By continuous cesium chloride gradient flotation it was shown that the myelin from the quaking animals consisted solely of a band corresponding to the heavier and smaller of the two bands found in normal controls. Cholesterol and glycolipids were lower and phospholipids (mainly phosphatidylcholine) and protein were higher in quaking animals than in controls. Also, phosphatidal-ethanolamine was decreased, and several consistent differences in the fatty acids (both unsubstituted and hydroxy) and aldehydes of the component lipids were found. In general there were smaller amounts of monounsaturated fatty acids in quaking animals. We suggest from these findings that myelin in the quaking mouse has certain compositional similarities with juvenile myelin, but it may be an abnormal type of myelin.

Topics: Animals; Body Weight; Brain; Central Nervous System Diseases; Centrifugation, Density Gradient; Cerebrosides; Cholesterol; Chromatography, Gas; Chromatography, Thin Layer; Fatty Acids; Female; Mice; Mice, Inbred Strains; Mutation; Myelin Sheath; Organ Size; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Seizures; Sphingomyelins; Sulfoglycosphingolipids