A COMPARATIVE STUDY OF THE METABOLISM OF DE NOVO SYNTHESIZED FATTY ACIDS FROM ACETATE AND GLUCOSE, AND EXOGENOUS FATTY ACIDS, IN SLICES OF RABBIT CEREBRAL CORTEX DURING DEVELOPMENT

Abstract

Abstract— Slices of rabbit cerebral cortex, from the foetal stage to the adult have been used to compare lipid synthesis from fatty acids synthesized de novo from [U‐14C]glucose and [1‐14C]acetate, with lipid synthesis from exogenous albumin‐bound [1‐14C]palmitate. Incorporation into cellular lipid has been determined in terms of DNA, protein, wet wt. of tissue and wet weight of whole brain. On a wet wt. basis, maximum incorporation of glucose carbon into lipid occurred in the foetal brain while lipid synthesis from acetate and palmitate was maximum at 4–14 days after birth. Glucose and acetate were incorporated into a diversity of lipids (with increasing amounts of phosphatidylcholine synthesized during maturation), while palmitate was incorporated into the free fatty acid and triglyceride fractions. A greater proportion of acetate was incorporated into fatty acids of chain‐length longer than C16 compared with the incorporation of palmitate. However, on a molar basis de novo synthesized and exogenous palmitate were elongated, desaturated and incorporated into phospholipids at a similar rate, while exogenous palmitate was incorporated to a greater extent than de nova synthesized fatty acid into the triglyceride fraction. This difference in metabolism may be due to the different size of the non‐esterified fatty acid pool in the two situations. At the period of their most active formation, the very long‐chain fatty acids may be synthesized from a pool of the C18 series of fatty acids (saturated and monoenoic) not in equilibrium with the bulk of C18 acids in cerebral lipids. This could be a pool of acyl groups derived from ethanolamine phospholipids.

Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite

“…This is particularly evident in that the rates of cerebral glucose utilization, based on the uptake of 2-[ 14 C]deoxyglucose, approach 60 mol/g/h (recalculated from Brown and Lorden, 1989;Choi et al, 2001;Simpson et al, 2007). Furthermore, direct measurements in the in vitro brain slice preparation demonstrated that approximately 385 nmol/g/h of glucose is completely oxidized, which sharply contrasts with the extremely low rates of fatty acid (i.e., palmitate) oxidation, which amount only to 0.02 nmol/g/h (Carey, 1975). This suggests that fatty acids are not an important energy substrate for the brain.…”

“…Nonetheless, fatty acids and their metabolites are recognized as important cellular messengers in the brain. This supposition is evinced from the extremely low rates of fatty acid ␤-oxidation observed in brain slice preparations compared with the rates of fatty acid incorporation into various intracellular lipids (Carey, 1975), as well as the low rates of fatty acid ␤-oxidation relative to fatty acid activation (i.e., esterification) in neuron-derived neuro2A cells (Pei et al, 2003). The mechanism(s) by which fatty acids and their metabolites influence the CNS, particularly the hypothalamic regulation of energy homeostasis, has become an area of intense investigation (section II.D).…”

“…These fatty acyl CoA molecules have several fates, including mitochondrial uptake and subsequent fatty acid ␤-oxidation (the rates of which are extremely low in brain) or the conversion into various structural and signaling lipid molecules, including phospholipids, triacylglycerol, diacylglycerol, and fatty acyl carnitine species. With regard to palmitate metabolism, in vitro studies using the rabbit brain slice preparation and radiolabeled palmitate ( [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitate) have demonstrated that the majority of palmitate is incorporated into the neutral lipid fraction, which is itself primarily represented via triacylglycerol and nonesterified free fatty acids (Carey, 1975). Furthermore, the desaturation and elongation of palmitate is very low, whereas a larger portion can be found in fatty acids of chain length less than C 16 (Carey, 1975).…”

“…With regard to palmitate metabolism, in vitro studies using the rabbit brain slice preparation and radiolabeled palmitate ( [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitate) have demonstrated that the majority of palmitate is incorporated into the neutral lipid fraction, which is itself primarily represented via triacylglycerol and nonesterified free fatty acids (Carey, 1975). Furthermore, the desaturation and elongation of palmitate is very low, whereas a larger portion can be found in fatty acids of chain length less than C 16 (Carey, 1975). The largest lipid pool containing HYPOTHALAMIC MALONYL COA CONTROL OF APPETITE radiolabeled palmitate is the phospholipid pool, where the majority of palmitate label is incorporated into phosphatidylcholine (Miller et al, 1987).…”

The Pentose Phosphate Pathway in Brain during Development

“…Our data tend to confirm this, for the high pentose pathway activity which we show in 3-day-old brain is not coincident temporally with the period of myelination (Jacobson, 1963) when lipid synthetic activity is brisk. Maximum incorporation of acetate and palmitate into cerebral cortex lipids occurs in the second postnatal week (Patel and Tonkonow, 1974;Carey, 1975).…”