Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

Abstract

Metabolic disorders, particularly aberrations in lipid homeostasis, such as obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest together as the metabolic syndrome (MetS). Despite major advances in our understanding of the pathogenesis of these disorders, the prevalence of the MetS continues to rise. It is becoming increasingly apparent that intermediary metabolism within the central nervous system is a major contributor to the regulation of systemic metabolism. In particular, lipid metabolism within the brain is tightly regulated to maintain neuronal structure and function and may signal nutrient status to modulate metabolism in key peripheral tissues such as the liver. There is now a growing body of evidence to suggest that fatty acid (FA) sensing in hypothalamic neurons via accumulation of FAs or FA metabolites may signal nutritional sufficiency and may decrease hepatic glucose production, lipogenesis, and VLDL-TG secretion. In addition, recent studies have highlighted the existence of liver-related neurons that have the potential to direct such signals through parasympathetic and sympathetic nervous system activity. However, to date whether these liver-related neurons are FA sensitive remain to be determined. The findings discussed in this review underscore the importance of the autonomic nervous system in the regulation of systemic metabolism and highlight the need for further research to determine the key features of FA neurons, which may serve as novel therapeutic targets for the treatment of metabolic disorders.

Diurnal variability of cerebral metabolites in healthy human brain with 2D localized correlation spectroscopy (2D L‐COSY)

“…Similar to homocarnosine, which showed an increase of +16%, GSH plays a vital role as an intracellular antioxidant in the defense against reactive oxygen species, with peak expression of GSH in human brain thought to be around late night, which agrees with our findings of increased GSH (+37.5%). Lipid metabolism in the brain is a complex and dynamic process and each day up to 8% of long‐chain polyunsaturated fatty acids are actively turned over and replaced by plasma transported fatty acids . The diurnal effects of lipids in this study may be explained by the fact that lipid metabolism in the brain is influenced by food intake .…”

“…Lipid metabolism in the brain is a complex and dynamic process and each day up to 8% of long-chain polyunsaturated fatty acids are actively turned over and replaced by plasma transported fatty acids. 32 The diurnal effects of lipids in this study may be explained by the fact that lipid metabolism in the brain is influenced by food intake. 33 Since a 2D L-COSY sequence without outer volume suppression pulses was used, a minimal, yet reproducible, extravoxel lipid contamination was tolerated.…”

Plasmalogen deficiency and neuropathology in Alzheimer's disease: Causation or coincidence?

“…Lipids play critical structural and physiological roles in the brain [6]. Brain has the second‐highest lipid content after the adipose tissue with lipids consisting about 50% of the dry weight of the brain [7]. However, phospholipids predominate in the brain in contrast to triglyceride dominance in the adipose tissue [7].…”

“…Brain has the second‐highest lipid content after the adipose tissue with lipids consisting about 50% of the dry weight of the brain [7]. However, phospholipids predominate in the brain in contrast to triglyceride dominance in the adipose tissue [7]. Mono‐ and polyunsaturated fatty acids such as oleic acid, arachidonic acid, and docosahexaenoic acid are abundant in the brain tissue with phospholipids acting as reservoirs of these fatty acids [8].…”

Comparison between thaw-mounting and use of conductive tape for sample preparation in ToF-SIMS imaging of lipids in Drosophila microRNA-14 model

“…Hence, a deep understanding of the spatial distributions of the relevant biomolecular components, as well as the mechanistic effects of exogenous interferences in brain functions, plays a key role during drug discovery. [21][22][23][24] Consequently, a proper sampling protocol is essential for obtaining the ex vivo molecular locations by mass spectrometry analysis.…”