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Ketone Bodies Starvation

Food Intake And Starvation Induce Metabolic Changes

Food Intake And Starvation Induce Metabolic Changes

The well-fed, or postabsorptive, state. After we consume and digest an evening meal, glucose and amino acids are transported from the intestine to the blood. The dietary lipids are packaged into chylomicrons and transported to the blood by the lymphatic system. This fed condition leads to the secretion of insulin, which is one of the two most important regulators of fuel metabolism, the other regulator being glucagon. The secretion of the hormone insulin by the β cells of the pancreas is stimulated by glucose and the parasympathetic nervous system (Figure 30.15). In essence, insulin signals the fed state—it stimulates the storage of fuels and the synthesis of proteins in a variety of ways. For instance, insulin initiates protein kinase cascades—it stimulates glycogen synthesis in both muscle and the liver and suppresses gluconeogenesis by the liver. Insulin also accelerates glycolysis in the liver, which in turn increases the synthesis of fatty acids. The liver helps to limit the amount of glucose in the blood during times of plenty by storing it as glycogen so as to be able to release glucose in times of scarcity. How is the excess blood glucose present after a meal removed? Insulin accelerates the uptake of blood glucose into the liver by GLUT2. The level of glucose 6-phosphate in the liver rises because only then do the catalytic sites of glucokinase become filled with glucose. Recall that glucokinase is active only when blood-glucose levels are high. Consequently, the liver forms glucose 6-phosphate more rapidly as the blood-glucose level rises. The increase in glucose 6-phosphate coupled with insulin action leads to a buildup of glycogen stores. The hormonal effects on glycogen synthesis and storage are reinforced by a direct action of glucose itself. Phosphor Continue reading >>

A Monocarboxylate Transporter Required For Hepatocyte Secretion Of Ketone Bodies During Fasting

A Monocarboxylate Transporter Required For Hepatocyte Secretion Of Ketone Bodies During Fasting

Abstract To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by adequate nutrition. Adult rmn mutants show increased liver neutral lipids and induction of hepatic lipid biosynthetic genes when fasted. Positional cloning of the rmn locus reveals a loss-of-function mutation in slc16a6a (solute carrier family 16a, member 6a), a gene that we show encodes a transporter of the major ketone body β-hydroxybutyrate. Restoring wild-type zebrafish slc16a6a expression or introducing human SLC16A6 in rmn mutant livers rescues the mutant phenotype. Radiotracer analysis confirms that loss of Slc16a6a function causes diversion of liver-trapped ketogenic precursors into triacylglycerol. Underscoring the importance of Slc16a6a to normal fasting physiology, previously fed rmn mutants are more sensitive to death by starvation than are wild-type larvae. Our unbiased, forward genetic approach has found a heretofore unrecognized critical step in fasting energy metabolism: hepatic ketone body transport. Since β-hydroxybutyrate is both a major fuel and a signaling molecule in fasting, the discovery of this transporter provides a new direction for modulating circulating levels of ketone bodies in metabolic diseases. Continue reading >>

Renal Conservation Of Ketone Bodies During Starvation☆

Renal Conservation Of Ketone Bodies During Starvation☆

Abstract Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 ± 10 μmoles/min on day 3 to 106 ± 15, 89 ± 10, and 96 ± 10 μmoles/min on days 10, 17, and 24 respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 ± 27 μmoles/min on day 3 to 419 ± 53, 399 ± 25, and 436 ± 53 μmoles/min on days 10, 17, and 24 respectively. Both acetoacetate and beta-hydroxybuyyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation of 450–500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations. Continue reading >>

How Does The Body Adapt To Starvation?

How Does The Body Adapt To Starvation?

- [Instructor] In this video, I want to explore the question of how does our body adapt to periods of prolonged starvation. So in order to answer this question, I actually think it's helpful to remind ourselves first of a golden rule of homeostasis inside of our body. So in order to survive, remember that our body must be able to maintain proper blood glucose levels. I'm gonna go ahead and write we must be able to maintain glucose levels in our blood, and this is important even in periods of prolonged starvation, because it turns out that we need to maintain glucose levels above a certain concentration in order to survive, even if that concentration is lower than normal. And this of course brings up the question, well, how does our body maintain blood glucose levels? So let's go ahead and answer this question by starting off small. Let's say we have a mini case of starvation, let's say three or four hours after a meal. Your blood glucose levels begin to drop, and so what does your body do to resolve that? Well, at this point, it has a quick and easy solution. It turns to its glycogen stores in the liver. Remember that our body stores up these strings of glucose inside of our body so that we can easily pump it back into the blood when we're not eating. But unfortunately humans only have enough glycogen stores to last us about a day, so after a day of starvation, our body's pretty much reliant exclusively on the metabolic pathways involved in gluconeogenesis, which if you remember is the pathway by which we produce new or neo glucose. And we produce this glucose from non-carbohydrate precursor molecules. So let's think about what else we have in our body. Remember that our other two major storage fuels are fats, and we usually think about fatty acids containing most of th Continue reading >>

Metabolism And Ketosis

Metabolism And Ketosis

Dr. Eades, If the body tends to resort to gluconeogenesis for glucose during a short-term carbohydrate deficit, are those who inconsistently reduce carb intake only messing things up by not effecting full blown ketosis? If the body will still prefer glucose as main energy source unless forced otherwise for at least a few days, is it absolutely necessary to completely transform metabolism for minimal muscle loss? Also, if alcohol is broken down into ketones and acetaldehyde, technically couldn’t you continue to drink during your diet or would the resulting gluconeogenesis inhibition from alcohol lead to blood glucose problems on top of the ketotic metabolism? Would your liver ever just be overwhelmed by all that action? I’m still in high school so hypothetical, of course haha… Sorry, lots of questions but I’m always so curious. Thank you so much for taking the time to inform the public. You’re my hero! P.S. Random question…what’s the difference between beta and gamma hydroxybutyric acids? It’s crazy how simple orientation can be the difference between a ketone and date rape drug…biochem is so cool! P.P.S. You should definitely post the details of that inner mitochondrial membrane transport. I’m curious how much energy expenditure we’re talkin there.. Keep doin your thing! Your Fan, Trey No, I don’t think people are messing up if they don’t get into full-blown ketosis. For short term low-carb dieting, the body turns to glycogen. Gluconeogenesis kicks in fairly quickly, though, and uses dietary protein – assuming there is plenty – before turning to muscle tissue for glucose substrate. And you have the Cori cycle kicking in and all sorts of things to spare muscle, so I wouldn’t worry about it. And you can continue to drink while low-carbing. Continue reading >>

Ketone Bodies Metabolism

Ketone Bodies Metabolism

1. Metabolism of ketone bodies Gandham.Rajeev Email:[email protected] 2. • Carbohydrates are essential for the metabolism of fat or FAT is burned under the fire of carbohydrates. • Acetyl CoA formed from fatty acids can enter & get oxidized in TCA cycle only when carbohydrates are available. • During starvation & diabetes mellitus, acetyl CoA takes the alternate route of formation of ketone bodies. 3. • Acetone, acetoacetate & β-hydroxybutyrate (or 3-hydroxybutyrate) are known as ketone bodies • β-hydroxybutyrate does not possess a keto (C=O) group. • Acetone & acetoacetate are true ketone bodies. • Ketone bodies are water-soluble & energy yielding. • Acetone, it cannot be metabolized 4. CH3 – C – CH3 O Acetone CH3 – C – CH2 – COO- O Acetoacetate CH3 – CH – CH2 – COO- OH I β-Hydroxybutyrate 5. • Acetoacetate is the primary ketone body. • β-hydroxybutyrate & acetone are secondary ketone bodies. • Site: • Synthesized exclusively by the liver mitochondria. • The enzymes are located in mitochondrial matrix. • Precursor: • Acetyl CoA, formed by oxidation of fatty acids, pyruvate or some amino acids 6. • Ketone body biosynthesis occurs in 5 steps as follows. 1. Condensation: • Two molecules of acetyl CoA are condensed to form acetoacetyl CoA. • This reaction is catalyzed by thiolase, an enzyme involved in the final step of β- oxidation. 7. • Acetoacetate synthesis is appropriately regarded as the reversal of thiolase reaction of fatty acid oxidation. 2. Production of HMG CoA: • Acetoacetyl CoA combines with another molecule of acetyl CoA to produce β-hydroxy β-methyl glutaryl CoA (HMC CoA). • This reaction is catalyzed by the enzyme HMG CoA synthase. 8. • Mitochondrial HMG CoA is used for ketogenesis. Continue reading >>

Effect Of Fatty Acids, Ketone Bodies, Diabetes And Starvation On Pyruvate Metabolism In Rat Heart And Diaphragm Muscle

Effect Of Fatty Acids, Ketone Bodies, Diabetes And Starvation On Pyruvate Metabolism In Rat Heart And Diaphragm Muscle

IN alloxan diabetes the uptake and oxidation of pyruvate in vitro by rat ventricle muscle slices1 and diaphragm muscle2 is impaired, and the output of lactate may be increased. Moreover, in alloxan diabetic rats3 the blood concentration of pyruvate may be increased, and in dogs treated with growth hormone pyruvate tolerance is impaired and blood pyruvate elevated4. In earlier experiments5, evidence was obtained that impaired phosphorylation of glucose and of fructose-6-phosphate in hearts from alloxan diabetic or starved rats could result from enhanced respiration of fatty acids and ketone bodies and the suggestion was made that this might also be responsible for the high glycogen concentration of the heart in diabetes and starvation and for the myoglycostatic effect of growth hormone. In view of these findings, it seemed important to investigate the possibility that enhanced respiration of fatty acids and ketone bodies might also be responsible for abnormalities of pyruvate metabolism in muscles of alloxan diabetic rats and in animals treated with growth hormone. Continue reading >>

Ketone Bodies As A Fuel For The Brain During Starvation

Ketone Bodies As A Fuel For The Brain During Starvation

THE STATUS OF OUR KNOWLEDGE OF STARVATION AND BRAIN METABOLISM IN HUMANS WHEN I BEGAN MY RESEARCH This story begins in the early 1960s when the general level of knowledge about whole-body metabolism during human starvation was grossly deficient. This was partly caused by a lack of accurate and specific methods for measuring hormones and fuels in biological fluids, which became available about 1965.11 Rigidly designed protocols for studying human volunteers or obese patients, who underwent semi- or total starvation for prolonged periods of time, were not widely employed, and much of the published data regarding metabolic events during starvation were not readily accessible. To complicate matters further, a great deal of the available data was confusing because much of the supposition regarding mechanisms used by the body to survive prolonged periods of starvation was based upon information that was obtained from nonstandardized and often erroneous procedures for studying metabolism. For example, the rate of urinary nitrogen excretion during starvation was sometimes confounded by the consumption of carbohydrate during the studies. Today, students of biochemistry take for granted the fact that tissues of the human body have a hierarchy of fuel usage. They know that the brain, an organ devoted to using glucose, can switch to use ketone bodies during prolonged starvation (2–3 days), thus sparing glucose for other tissues (i.e. red blood cells must use glucose as a fuel; without mitochondria, they have no choice!). However, this fundamental insight into human metabolism was not recognized in the early 1960s, when my research in this area began. How this simple but fundamental fact that ketone bodies provide critical fuels for the brain was discovered and its implication for Continue reading >>

Ketones

Ketones

Excess ketones are dangerous for someone with diabetes... Low insulin, combined with relatively normal glucagon and epinephrine levels, causes fat to be released from fat cells, which then turns into ketones. Excess formation of ketones is dangerous and is a medical emergency In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketones can develop. What are ketones and why do I need to know about them? Ketones and ketoacids are alternative fuels for the body that are made when glucose is in short supply. They are made in the liver from the breakdown of fats. Ketones are formed when there is not enough sugar or glucose to supply the body’s fuel needs. This occurs overnight, and during dieting or fasting. During these periods, insulin levels are low, but glucagon and epinephrine levels are relatively normal. This combination of low insulin, and relatively normal glucagon and epinephrine levels causes fat to be released from the fat cells. The fats travel through the blood circulation to reach the liver where they are processed into ketone units. The ketone units then circulate back into the blood stream and are picked up by the muscle and other tissues to fuel your body’s metabolism. In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketone Continue reading >>

The Fat-fueled Brain: Unnatural Or Advantageous?

The Fat-fueled Brain: Unnatural Or Advantageous?

Disclaimer: First things first. Please note that I am in no way endorsing nutritional ketosis as a supplement to, or a replacement for medication. As you’ll see below, data exploring the potential neuroprotective effects of ketosis are still scarce, and we don’t yet know the side effects of a long-term ketogenic diet. This post talks about the SCIENCE behind ketosis, and is not meant in any way as medical advice. The ketogenic diet is a nutritionist’s nightmare. High in saturated fat and VERY low in carbohydrates, “keto” is adopted by a growing population to paradoxically promote weight loss and mental well-being. Drinking coffee with butter? Eating a block of cream cheese? Little to no fruit? To the uninitiated, keto defies all common sense, inviting skeptics to wave it off as an unnatural “bacon-and-steak” fad diet. Yet versions of the ketogenic diet have been used to successfully treat drug-resistant epilepsy in children since the 1920s – potentially even back in the biblical ages. Emerging evidence from animal models and clinical trials suggest keto may be therapeutically used in many other neurological disorders, including head ache, neurodegenerative diseases, sleep disorders, bipolar disorder, autism and brain cancer. With no apparent side effects. Sound too good to be true? I feel ya! Where are these neuroprotective effects coming from? What’s going on in the brain on a ketogenic diet? Ketosis in a nutshell In essence, a ketogenic diet mimics starvation, allowing the body to go into a metabolic state called ketosis (key-tow-sis). Normally, human bodies are sugar-driven machines: ingested carbohydrates are broken down into glucose, which is mainly transported and used as energy or stored as glycogen in liver and muscle tissue. When deprived of d Continue reading >>

Ketone Bodies

Ketone Bodies

Ketone bodies Acetone Acetoacetic acid (R)-beta-Hydroxybutyric acid Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2], alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy.[3] In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids).[1] They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted (these glycogen stores are depleted after only 24 hours of fasting)[1]. When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted Continue reading >>

Glucose Metabolism In Rat Skeletal Muscle At Rest: Effect Of Starvation, Diabetes, Ketone Bodies And Free Fatty Acids

Glucose Metabolism In Rat Skeletal Muscle At Rest: Effect Of Starvation, Diabetes, Ketone Bodies And Free Fatty Acids

The influence of starvation, diabetic ketoacidosis, ketone bodies and free fatty acids on glucose metabolism in resting skeletal muscle was studied in the isolated perfused rat hindquarter perparation and in intact rats. In the hindquarter preparation, the provision of 1.3 mM oleate, 1 mM octanoate or 2 mM acetoacetate did not alter the uptake of glucose in the presence of insulin. In contrast, glucose uptake in the presence of insulin was significantly depressed in hindquarters of rats with diabetic ketosis. In fed, fasted and diabetic rats the distribution space of glucose in skeletal muscle in vivo ranged between 15 to 20 per cent (extracellular space, 18 to 20 per cent), indicating that transport into the cell and not phosphorylation was rate-limiting for glucose uptake. The administration of glucose and insulin did not increase the glucose distribution space in fed or fasted rats; however, it caused a marked increase in tissue lactate in the fasted group, suggesting inhibition of pyruvate oxidation. The concentrations of hexose monophosphates in skeletal muscle freeze-clamped in vivo were very similar in the three groups, indicating phosphofructokinase was not inhibited in the fasted or diabetic rats. There were also no major differences in the concentrations of citrate, glycerolphosphate, ATP, ADP and AMP: the concentration of acetyl CoA was increased in both forty-eight hour fasted and diabetic rats and free CoA was diminished in the diabetic rats. Tissue glycogen waslower in fasted and diabetic than in fed rats. The data suggest that in resting skeletal muscle there is no inhibition of glucose metabolism by exogenous fatty acids and ketone bodies anaiagous to that which occurs in heart and diaphragm. The rate limiting step in glucose uptake appears to be its tra Continue reading >>

Starvation Response

Starvation Response

Starvation response in animals is a set of adaptive biochemical and physiological changes that reduce metabolism in response to a lack of food.[1] Equivalent or closely related terms include famine response, starvation mode, famine mode, starvation resistance, starvation tolerance, adapted starvation, adaptive thermogenesis, fat adaptation, and metabolic adaptation. Starvation contributes to tolerance during infection, as nutrients become limited when they are sequestered by host defenses and consumed by proliferating bacteria. One of the most important causes of starvation induced tolerance in vivo is biofilm growth, which occurs in many chronic infections. Starvation in biofilms is due to nutrient consumption by cells located on the periphery of biofilm clusters and by reduced diffusion of substrates through the biofilm. Biofilm bacteria shows extreme tolerance to almost all antibiotic classes, and supplying limiting substrates can restore sensitivity. In humans[edit] Starvation mode is a state in which the body responds to prolonged periods of low energy intake. During short periods of energy abstinence, the human body burns primarily free fatty acids from body fat stores, along with small amounts of muscle tissue to provide required glucose for the brain. After prolonged periods of starvation the body has depleted its body fat and begins to burn primarily lean tissue and muscle as a fuel source. Ordinarily, the body responds to reduced energy intake by burning fat reserves and consuming muscle and other tissues. Specifically, the body burns fat after first exhausting the contents of the digestive tract along with glycogen reserves stored in liver cells.[2] After prolonged periods of starvation, the body uses the proteins within muscle tissue as a fuel source. People Continue reading >>

Ketoacidosis

Ketoacidosis

GENERAL ketoacidosis is a high anion gap metabolic acidosis due to an excessive blood concentration of ketone bodies (keto-anions). ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) are released into the blood from the liver when hepatic lipid metabolism has changed to a state of increased ketogenesis. a relative or absolute insulin deficiency is present in all cases. CAUSES The three major types of ketosis are: (i) Starvation ketosis (ii) Alcoholic ketoacidosis (iii) Diabetic ketoacidosis STARVATION KETOSIS when hepatic glycogen stores are exhausted (eg after 12-24 hours of total fasting), the liver produces ketones to provide an energy substrate for peripheral tissues. ketoacidosis can appear after an overnight fast but it typically requires 3 to 14 days of starvation to reach maximal severity. typical keto-anion levels are only 1 to 2 mmol/l and this will usually not alter the anion gap. the acidosis even with quite prolonged fasting is only ever of mild to moderate severity with keto-anion levels up to a maximum of 3 to 5 mmol/l and plasma pH down to 7.3. ketone bodies also stimulate some insulin release from the islets. patients are usually not diabetic. ALCOHOLIC KETOSIS Presentation a chronic alcoholic who has a binge, then stops drinking and has little or no oral food intake for a few days (ethanol and fasting) volume depletion is common and this can result in increased levels of counter regulatory hormones (eg glucagon) levels of free fatty acids (FFA) can be high (eg up to 3.5mM) providing plenty of substrate for the altered hepatic lipid metabolism to produce plenty of ketoanions GI symptoms are common (eg nausea, vomiting, abdominal pain, haematemesis, melaena) acidaemia may be severe (eg pH down to 7.0) plasma glucose may be depressed or normal or Continue reading >>

Ketone Body Metabolism In Lean Male Adults During Short-term Starvation, With Particular Reference To Forearm Muscle Metabolism

Ketone Body Metabolism In Lean Male Adults During Short-term Starvation, With Particular Reference To Forearm Muscle Metabolism

1. Thirty-three arteriovenous forearm catheterization studies were carried out in 19 lean subjects starving for 12–14 h(n = 13), 30–36 h (n = 7) and 60–66 h (n = 13). Forearm blood flow was measured in order to calculate the flux of various substrates. At the same time, whole-body oxidation of fat, carbohydrate and protein was calculated using indirect calorimetry and urinary nitrogen excretion. 2. After an overnight fast (12–14 h), whole-body resting energy expenditure was accounted for by the oxidation of protein (15%), carbohydrate (17%) and fat (68%). At 30–36 h and 60–66 h of starvation, essentially all the non-protein energy was derived from the oxidation of fat (directly plus indirectly via ketone bodies). 3. After an overnight fast, acetoacetate and 3-hydroxybutyrate were taken up by forearm muscle at a rate which could account for 5% of the resting O2 consumption of this tissue. As starvation progressed, forearm muscle took up more acetoacetate and released 3-hydroxybutyrate so that the net uptake of ketone bodies was sufficient to account for about 10% of the resting O2 consumption at 30–36 h of starvation and about 20% at 60–66 h of starvation. 4. The uptake of circulating non-esterified fatty acids by forearm muscle accounted for a greater proportion of the forearm O2 consumption than the uptake of ketone bodies at all times studied. The release of lactate and alanine was significantly greater at 36–40 h and 60–66 h of starvation compared with 12–14 h of starvation, but that of glucose did not change significantly. 5. The results suggest that during early starvation: (a) the release of 3-hydroxybutyrate by muscle (36–66 h starvation) contributes to the circulating 3-hydroxybutyrate concentration, (b) the contribution of ketone bodies Continue reading >>

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