The aldehyde 4HNE is the final product of reactive oxygen species formation and its overproduction can result in mitochondria dysfunction, lipid peroxidation, 40 and hepatic damage. Mitochondrial CK uMitCK is particularly sensitive to oxidative damage, 43 and we observed increased levels of uMitCk in the liver of both TBI and fructose animals, suggesting an increase in mitochondrial enzymes in response to oxidative damage. These results provide an indication for the effects of TBI on cell energy metabolism and inflammation in the liver, as previously suggested in other disease models.
Hepatic lipid droplets LDs are major cellular organelles involved in the storage of neutral lipids such as triglycerides, steryl esters, and retinyl esters. Fatty acid synthase FAS is a key lipogenic enzyme commonly involved in fatty acid synthesis. GH is a key player in liver lipid metabolism such that disturbances in GH signaling promote excessive lipid buildup in the liver as well as in other organs. GH signaling is often altered following TBI 62 and results in dysregulation of glucose homeostasis.
Moreover, the response of GH axis to trauma is biphasic, with acute and chronic phases. Excessive amounts of GH oppose the effects of insulin in the liver and peripheral tissues. Similar findings were noted when total deletion of the GHR in liver showed fourfold increase in circulating GH along with insulin resistance, glucose intolerance, and elevated circulating free fatty acids. In conclusion, our study uncovers the potential bidirectional interactions between the brain and liver after brain injury. These experimental data suggest that an important aspect of the TBI pathology takes place in the periphery with subsequent repercussions for the brain.
Furthermore, a metabolic perturbation induced by a short period of high fructose consumption potentiates the effects of TBI on systemic metabolism. These data piece together to reveal the compelling possibility that a metabolic perturbation carried by diet is a predictor of worse outcome in the pathophysiology of TBI.
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Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article. Abstract Scope The action of brain disorders on peripheral metabolism is poorly understood. Methods and Results It is found that TBI affects glucose metabolism and signaling proteins for insulin and growth hormone in the liver; these effects are exacerbated by fructose ingestion.
Conclusion Results reveal the impact of TBI on systemic metabolism and the aggravating action of fructose. Figure 1 Open in figure viewer PowerPoint. Fructose and TBI impair hepatic insulin signaling and systemic glucose regulation. E Increased plasma insulin levels in fructose and TBI animals as compared to sham animals. Figure 2 Open in figure viewer PowerPoint. Proteins shown in A and C were probed on the same membrane. Figure 3 Open in figure viewer PowerPoint. Fructose and TBI promote hepatic inflammation, oxidative stress, and mitochondrial dysfunction.go to site
The Functions of Fats in the Body
This might even offer a new way of analysis to address how lipid signaling for instance through the addition of a lipid tag changes cellular localization of certain proteins. Last but not least, the promising data on lipid-based signals via 1 H-MRS, which correlate with in vivo neurogenesis, might open up completely new avenues to study this important process in a non-invasive way in humans. It is needless to say that such a possibility to study neurogenesis in humans, both in healthy subjects and in patients with neurological diseases, would revolutionize thefield.
I would like to thank Sebastian Jessberger, Darcie Moore and Ruth Beckervordersandforth for critical comments on the manuscript. Kriegstein A , Alvarez-Buylla A. Annu Rev Neurosci. Annu Rev Cell Dev Biol. Malformations of cortical development. Sun T , Hevner RF. Growth and folding of the mammalian cerebral cortex: From molecules to malformations. Nat Rev Neurosci. Adult Neurogenesis and Psychiatric Disorders. Cold Spring Harb Perspect Biol. Functions and Dysfunctions of Adult Hippocampal Neurogenesis.
Adult mammalian neural stem cells and neurogenesis: Five decades later. Cell Stem Cell. Analytical strategies for studying stem cell metabolism. Front Biol. Metabolic plasticity in stem cell homeostasis and differentiation. Ito K , Suda T.
Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism
Metabolic requirements for the maintenance of self-renewing stem cells. Nat Rev Mol Cell Biol. Proliferation control in neural stem and progenitor cells. Knobloch M , Jessberger S. Metabolic control of adult neural stem cell behavior. Fahy E. A comprehensive classification system for lipids. J Lipid Res. Bieberich E. Neurochem Res. Glatz JFC. Lipids and lipid binding proteins: A perfect match. Fatty acid binding proteins in brain development and disease. Int J Dev Biol. Fatty acid binding proteins and the nervous system: Their impact on mental conditions.
Neuroscience Research. The expression pattern of a novel gene encoding brain-fatty acid binding protein correlates with neuronal and glial cell development. Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains. J Chem Neuroanat. Brain lipid-binding protein is a direct target of Notch signaling in radial glial cells. Role of Fabp7, a downstream gene of Pax6, in the maintenance of neuroepithelial cells during early embryonic development of the rat cortex.
Journal of Neuroscience. Radial glia serve as neuronal progenitors in all regions of the central nervous system. Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene. Eur J Neurosci. Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype. Mackay TFC , editor. PLoS Biol. The effects of Fabp7 and Fabp5 on postnatal hippocampal neurogenesis in the mouse. Stem Cells. Astrocyte-expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons.
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Prostaglandins, leukotrienes and essential fatty acids. Schoenfeld P , Reiser G. Why does brain metabolism not favor burning of fattyacids to provide energy? Neural stem cells in the adult subventricular zone oxidize fatty acids to produce energy and support neurogenic activity. Inborn errors of long-chain fatty acid b-oxidation link neural stem cell self-renewal to autism. Cell Reports. Obesity, inflammation, and cancer. Annu Rev Pathol. High-fat diet impairs hippocampal neurogenesis in male rats.
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International Journal of Developmental Neuroscience. Kokoeva MV. Once in the circulation, they can either go to the liver or be stored in fat cells adipocytes that comprise adipose fat tissue found throughout the body. To obtain energy from fat, triglycerides must first be broken down by hydrolysis into their two principal components, fatty acids and glycerol. This process, called lipolysis , takes place in the cytoplasm. The glycerol that is released from triglycerides after lipolysis directly enters the glycolysis pathway as DHAP.
Because one triglyceride molecule yields three fatty acid molecules with as much as 16 or more carbons in each one, fat molecules yield more energy than carbohydrates and are an important source of energy for the human body. Triglycerides yield more than twice the energy per unit mass when compared to carbohydrates and proteins. Therefore, when glucose levels are low, triglycerides can be converted into acetyl CoA molecules and used to generate ATP through aerobic respiration.
This fatty acyl CoA combines with carnitine to create a fatty acyl carnitine molecule, which helps to transport the fatty acid across the mitochondrial membrane. Once inside the mitochondrial matrix, the fatty acyl carnitine molecule is converted back into fatty acyl CoA and then into acetyl CoA Figure 3. If excessive acetyl CoA is created from the oxidation of fatty acids and the Krebs cycle is overloaded and cannot handle it, the acetyl CoA is diverted to create ketone bodies.
These ketone bodies can serve as a fuel source if glucose levels are too low in the body. Ketones serve as fuel in times of prolonged starvation or when patients suffer from uncontrolled diabetes and cannot utilize most of the circulating glucose. In both cases, fat stores are liberated to generate energy through the Krebs cycle and will generate ketone bodies when too much acetyl CoA accumulates.
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Organs that have classically been thought to be dependent solely on glucose, such as the brain, can actually use ketones as an alternative energy source. This keeps the brain functioning when glucose is limited. When ketones are produced faster than they can be used, they can be broken down into CO 2 and acetone. The acetone is removed by exhalation. This effect provides one way of telling if a diabetic is properly controlling the disease.
The carbon dioxide produced can acidify the blood, leading to diabetic ketoacidosis, a dangerous condition in diabetics. Ketones oxidize to produce energy for the brain. The carbon within the acetoacetyl CoA that is not bonded to the CoA then detaches, splitting the molecule in two. These two acetyl CoA molecules are then processed through the Krebs cycle to generate energy Figure 5. When glucose levels are plentiful, the excess acetyl CoA generated by glycolysis can be converted into fatty acids, triglycerides, cholesterol, steroids, and bile salts.
This process, called lipogenesis , creates lipids fat from the acetyl CoA and takes place in the cytoplasm of adipocytes fat cells and hepatocytes liver cells. When you eat more glucose or carbohydrates than your body needs, your system uses acetyl CoA to turn the excess into fat. Although there are several metabolic sources of acetyl CoA, it is most commonly derived from glycolysis. Acetyl CoA availability is significant, because it initiates lipogenesis. Lipogenesis begins with acetyl CoA and advances by the subsequent addition of two carbon atoms from another acetyl CoA; this process is repeated until fatty acids are the appropriate length.