The Anatomy of Fat Burning – Function and Optimization

Dear blog readers,

Whenever the term “fat burning” comes up, the entire fitness world is abuzz. Along with building muscle, fat burning is one of the two main and recurring goals that people meticulously pursue at least every six months. The fitness industry offers countless ways to reach this goal. From losing weight through Weight Watchers to countless crash diets, challenges, and the like, everyone is trying to make money off the topic of weight loss and fat burning and get a slice of the pie that promises a lot of revenue. The dietary supplement industry also offers a wide range of “fat-burning” aids, which unfortunately sometimes leads to confusion and misconceptions. Advertising claims promise significant results simply by taking a combination of certain substances, causing the actually important “big picture” to take a back seat.

Today’s article deals with the biochemical fundamentals of fat metabolism. At first glance, this sounds very boring and tedious, and indeed, you’ll have to grit your teeth today and power through the first, somewhat dry chapter. What I promise is that the effort will pay off, and you’ll be rewarded with crucial facts on the topic of fat burning.

Enjoy!

Lipids—the root of all evil?—Not really….

Even though lipids are responsible for the formation of excess fat deposits in the first place, they are not the enemy—quite the opposite. In addition to their role as the most energy-dense storage compound for all life forms, lipids are absolutely essential because they form the structure of all membranes and serve as precursors for the synthesis of fat-soluble vitamins, bile acids, and steroid hormones. In addition to obtaining fatty acids from food, we also produce lipids on our own, with the exception of the essential ones.

The Path of Dietary Fat in Our Body

Dietary lipids enter the bloodstream via the intestines as part of the digestion and absorption process. With the exception of free cholesterol, all dietary components must be broken down into their constituent parts before they can be absorbed. In the case of lipids, this occurs through a process known as hydrolytic cleavage. Special enzymes, known as lipases, are required for this process. Pancreatic triacylglycerol lipase is responsible for breaking down the main component of dietary fat. The term “pancreatic” indicates that this enzyme originates in the pancreas. Once cleavage has taken place, so-called micelles must form for absorption; these micelles enclose not only fatty acids but also compounds such as fat-soluble vitamins. In this form, they are then transported from the intestine (via the so-called mucosal cells of the duodenum) first into the intestinal lymphatic vessels and then into the blood plasma.

Once in the blood, the task is to make the micelles transportable, which requires binding them to specific proteins known as apolipoproteins. As part of this process, so-called lipoproteins are formed, which then migrate on to the liver or to so-called extrahepatic tissues. Lipids that reach the liver are either stored there, converted into ketone bodies, or packaged as VLDL (very low-density lipoprotein), released into the bloodstream, and distributed from there to extrahepatic tissues. Some of the lipids also travel directly to extrahepatic tissues, where they are either stored (adipose tissue) or burned through β-oxidation. Adipose tissue (adipocytes), in particular, is an excellent storage site for lipids in the form of triglycerides, as these constitute 95% of the cell mass there.

Interesting

The liver is capable of synthesizing lipids from glucose on its own.

Interesting

The adipose tissue of a normal-weight adult stores about 8 kg of triglycerides, which corresponds to an energy requirement of about 40 days.

Conclusion

Dietary fat must be broken down to allow for absorption. During transport, new fat structures are formed, into which fat-soluble vitamins are sometimes embedded, ultimately reaching the bloodstream. Once in the blood, fatty acids travel either directly to the liver or to other tissues, where they are either stored or burned.

Here’s what happens to lipids in our body

Lipids stored as triglycerides are mobilized when a need arises and are broken down by triglyceride lipases into glycerol and non-esterified fatty acids. This process consumes energy. The majority of the resulting glycerol and released fatty acids are then released into the blood and transported to tissues in need, where they are oxidized to produce energy.

Since triglycerides, as nonpolar compounds, cannot be transported across the cell membrane, they occur in the body only in the intestinal lumen as components of dietary lipids, in blood plasma as components of lipoprotein fractions, or intracellularly as stored triglycerides. To be transported across the cell membrane, they must therefore be broken down again. The enzymes responsible for this are lipoprotein lipase and intracellular lipases. The transport of lipids in the blood then takes place again via chylomicrons or VLDL. Upon arrival at the target cell, the breakdown process (hydrolysis) must occur once more, for which the enzyme lipoprotein lipase is required. Now, fatty acids and glycerol can be taken up by the target cells.

Conclusion

As nonpolar compounds, triglycerides (the storage form of fatty acids) cannot simply move from cell to cell; instead, they must be broken down, packaged into blood transport particles, and hydrolyzed again before they can be used for energy in the target cell.

Lipolysis

As energy stores, lipids (triglycerides) are found in nearly all tissues, but primarily, of course, in the adipocytes designated for this purpose—that is, in adipose tissue. When these stores are mobilized, the process is called lipolysis. This is a three-step process that yields 1 mol of glycerol and 3 mol of fatty acids. Enzymes are also required for the process of lipolysis; in this case, they are intracellular lipases. In adipose tissue, three different types of lipases are known, starting with adipose tissue triglyceride lipase (ATGL), which is highly active in white and brown adipose tissue, while its activity in skeletal and cardiac muscle is rather low. The so-called hormone-sensitive lipase (HSL) is found not only in adipose tissue but also in numerous other tissues, such as skeletal muscle, cardiac muscle, the brain, the testes, pancreatic beta cells, and the adrenal glands. It is known that HSL activity is subject to hormonal regulation by catecholamines, which makes HSL a very interesting enzyme. An estimated 5% of lipolytic activity in adipose tissue is ultimately attributable to the third group of enzymes, the so-called monoacylglycerol lipases.

Conclusion

Anyone planning to take on excess weight should keep the term “lipolysis” in mind, as this process represents the first step toward actual fat burning. Three enzymes are considered essential for lipolysis; the one of greatest interest to us is the so-called hormone-sensitive lipase.

β-Oxidation

Mobilizing triglycerides and drawing them out of adipose tissue is one thing; actually feeding them into the metabolic process is another. Of course, there must also be a corresponding need for what is known as β-oxidation. This refers to the biochemical breakdown of fatty acids, which takes place both in the mitochondrial matrix (within the mitochondria—the cell’s powerhouses) and in peroxisomes.

Mitochondrial β-oxidation

Mitochondria are found in cells with high energy demands, such as muscle cells, sensory cells, nerve cells, as well as in egg cells and heart muscle cells, and are involved in the breakdown of fatty acids and glucose as part of the citric acid cycle and the respiratory chain. They are the only site where complete oxidation of fatty acids takes place. For fatty acids to enter the cell, three steps are required, all of which involve the amino acid carnitine. The enzyme carnitine acyltransferase transfers fatty acid esters, while the carnitine-acylcarnitine antiporter transports the resulting acylcarnitine across the inner mitochondrial membrane in exchange for free carnitine.

Important

A carnitine deficiency, regardless of its cause, leads to a severe impairment of mitochondrial β-oxidation. The body’s endogenous synthesis of carnitine takes place primarily in the liver.

β-Oxidation in Peroxisomes

Peroxisomes also carry out the process of β-oxidation. They do so in an oxygen-dependent manner but independently of carnitine, since fatty acids are transported into the peroxisomes via a specific protein called adrenoleukodystrophy protein (ALDP). Unlike in mitochondria, long-chain fatty acids are not completely oxidized in peroxisomes but are instead only shortened.

The final energy product of β-oxidation is acetyl-CoA. A large portion of it is broken down in the citric acid cycle, but it can also be converted into ketone bodies in the liver. The liver cannot utilize ketone bodies itself, which is why it always releases them to other tissues—such as the brain—to meet their energy needs.

Why We Exhale Body Fat

During the oxidation of fatty acids, carbon dioxide and water are produced as end products in addition to energy. The oxidation of 10 g of body fat produces 28 kg of carbon dioxide (CO₂) and 11 kg of water (H₂O). These are mainly exhaled through the lungs, which means that the lungs are, in fact, the primary excretory organ for end products resulting from weight loss through fat loss. The water produced is excreted through breathing, as well as through urine, sweat, tears, feces, or other bodily fluids.

Conclusion

Fat burning does not take place in fat cells, but rather in tissues with high energy consumption—and within these tissues, primarily in the mitochondria of the cells. Without carnitine, mitochondrial β-oxidation (fat burning) and thus the complete oxidation of long-chain fatty acids is not possible. The final energy product of β-oxidation is called acetyl-CoA. It is largely used directly for energy production, but can also be converted into ketone bodies in the liver. Ultimately, we exhale a large portion of the burned body fat through our lungs.

Regulation of Fatty Acid Metabolism

In principle, when burning fat, our body acts solely according to the principle of efficiency, i.e.:

• Excess food intake promotes triglyceride storage
• Increased energy demand promotes lipolysis

Since these are two completely different processes, a sensitive regulatory mechanism must be in place to ensure constant homeostasis. In a state of excess food intake, insulin levels are usually high. This occurs alongside low levels of adrenaline, norepinephrine, and glucagon (which acts as an antagonist to insulin to stabilize blood sugar). In the event of food scarcity or increased energy demand, elevated concentrations of adrenaline and glucagon activate lipolysis while simultaneously inhibiting lipogenesis.

The rate at which β-oxidation occurs depends on the enzyme carnitine acyltransferase 1. High levels of thyroid hormone, as well as high levels of long-chain fatty acids in the blood (during increased lipolysis activity), induce this enzyme.

Conclusion

Fat is only burned when fatty acids from lipolysis are also “burned” through β-oxidation.

The following scenario shifts fat metabolism toward catabolism

• food scarcity
• high energy demand
• high thyroid hormone activity
• a high level of long-chain fatty acids
• low insulin levels
• high levels of catecholamines

The Liver’s Role in Fat Metabolism

The liver possesses active metabolic pathways for the breakdown of triglycerides and fatty acids, as well as for the formation of ketone bodies. It is also the site of bile acid production and is known to uptake fatty acids from the blood not only during a high-fat diet but also during catabolic metabolic states (food deprivation) or severe stress.

With a high-fat diet, triglycerides are increasingly taken up by the liver and activated into acyl-CoA, which in certain cases is then either used to form stored fat (triglycerides) or incorporated into lipoproteins.

During a high-fat diet, the liver acts as a temporary fat storage site, subsequently coordinating the redistribution of fat.

Catabolic metabolic states increase lipolysis in adipose tissue, leading to a rise in plasma fatty acid concentration, which in turn promotes uptake by the liver. Here, too, acyl-CoA is formed; this time, however, it enters the mitochondria via the carnitine system, where it undergoes β-oxidation. Ketone bodies may also be produced during this process.

Conclusion

Depending on the metabolic state, the liver either stores fat during anabolism or, during catabolism, directs it toward further energy utilization (β-oxidation and/or ketone body formation).

Carbohydrate and fat metabolism are interlinked

In a diet rich in carbohydrates and fatty acids, the carbohydrate component replenishes glycogen stores and meets energy needs. During the absorption phase, fatty acid oxidation occurs only if energy requirements cannot be met by the breakdown of carbohydrates and protein (gluconeogenesis). As a result, when there is a calorie surplus, dietary lipids are primarily stored in adipose tissue. The higher the carbohydrate content in the diet, the greater the likelihood that these carbohydrates will be converted into fatty acids, even though this process plays a relatively minor role in humans.

Conclusion

As long as enough calories and carbohydrates are consumed through food, our bodies store dietary lipids in adipose tissue. A significantly increased carbohydrate intake can also lead to the conversion of carbohydrates into fatty acids in humans under certain conditions.

How Food Deprivation Affects Substrate Supply

During food deprivation, a shortage of carbohydrates, fatty acids, and protein is assumed. The supply of glucose to glucose-dependent systems takes priority, which is why the following metabolic relationships come into play

• Hepatic glycogenolysis (breakdown of glycogen stores in the liver)
• Lipolysis and increased fatty acid oxidation in muscle and liver
• Ketone body formation in the liver
• Proteolysis (muscle protein breakdown)
• Gluconeogenesis (glucose synthesis from lactate, amino acids, and glycerol / up to 200 g/day)

Important

The metabolic changes mentioned are primarily driven by a decrease in insulin concentration and the resulting predominance of insulin antagonists (catecholamines and glucagon).

Conclusion

Fasting not only burns fat to compensate for the energy deficit but also leads to the breakdown of amino acids from the muscles.

Practical Insights from Biochemical Principles

From the theoretical foundations of fat metabolism, it is now relatively easy to derive practical insights for optimizing fat burning.

1. Input/Output – Too many calories inhibit lipolysis and β-oxidation.
2. Input/Output – Too many carbohydrates inhibit lipolysis and β-oxidation. In small amounts, they can even be converted into fat.
3. The presence of insulin inhibits catabolic processes in fat metabolism.
4. The presence of glucagon and catecholamines promotes catabolic processes in fat metabolism.
5. Thyroid hormone activity determines the rate of beta-oxidation.
6. Carnitine actively participates in mitochondrial fat burning.
7. Complete dietary restriction promotes not only lipolysis but also proteolysis.
8. Lipolysis alone does not necessarily mean fat burning.

1.

The absolute basic rule for fat burning is: “Eat less than you need.” No matter what strategy you plan to use in the fight against excess weight, if you eat more than you burn, not a single measure will be successful.

2.

A high-carb diet for fat loss? Hardly, since there are indeed several arguments against consuming large amounts of carbohydrates—even when you’re in a calorie deficit. Point 3 explains why.

3.

Insulin acts as an anabolic signaling molecule in our body and influences fat metabolism like no other. The presence of insulin thwarts any attempt to combat body fat, as it signals all cells to initiate anabolic processes and inhibit catabolic processes. Consistently consuming carbohydrates (and, incidentally, highly insulinogenic protein sources) throughout the day hinders fat burning, even in low-calorie situations.

4.

When energy intake is too low and even a slight deficiency of dietary sugar stabilizes blood sugar, lipolysis-promoting signaling molecules such as glucagon dominate. Catecholamines support lipolysis through their direct influence on HSL, the enzyme we’ve learned breaks down triglycerides to release stored fat. In addition to proper dietary measures, stimulants such as tyrosine, caffeine, theophylline, theobromine, ephedrine, pseudoephedrine, and even nicotine come into play here, all of which increase catecholamine levels. Cortisol, incidentally, also supports the lipolytic effect produced by catecholamines.

5.

Poor thyroid hormone activity can thwart efforts to maximize fat burning, as it prevents β-oxidation from being maintained at an optimal level. Therefore, any measures that result in insufficient levels of free, active thyroid hormone are detrimental to fat burning. Examples include regular, excessive, and prolonged cardio sessions or the regular consumption of large amounts of soy (in the absence of an adequate iodine intake).

6.

Without carnitine, it is actually impossible for long-chain fatty acids to be completely burned through mitochondrial β-oxidation. Carnitine does not have an independent fat-burning effect in this process; rather, it ensures that the fatty acids can even reach the mitochondria, where β-oxidation takes place. Carnitine is not considered an essential amino acid, which means that “normal” requirements can be met not only through dietary intake but also through the body’s own synthesis. Unfortunately, the widespread use of carnitine as a dietary supplement for fat burning must therefore be considered useless for anyone who does not exercise regularly. If physical activity places greater demands on fat metabolism—and thus on the mitochondria—the use of carnitine may potentially promote the burning of long-chain fatty acids.

7.

One reason why crash diets always lead to negative consequences has been described very clearly. In addition to increased lipolysis, food deprivation also leads to a significant breakdown of amino acids through proteolysis and gluconeogenesis in order to supply glucose-dependent systems with energy. This is a completely inefficient process that depletes active muscle tissue and thus triggers a decrease in basal metabolic rate—a nightmare for any athlete and the best argument for adopting a sensible strategy that promotes fat burning without losing muscle mass and opening the door to the yo-yo effect.

8.

Another distinction highlighted in today’s article is the difference between lipolysis and fat burning. Just because a fat cell releases fatty acids via catecholamine-mediated mechanisms does not necessarily mean that these fatty acids are actually burned for energy through β-oxidation. Such an imbalance occurs very frequently when people are under psychological stress or overdo it with stimulants. If cortisol dominates as the stress hormone, this leads to fatty acids in the blood being stored not only in the liver but increasingly in the abdominal area as well.

In practice, this means that stimulant-based and lipolysis-promoting dietary supplements can be used as desired, as long as energy requirements are increased through physical activity to the extent that the released fatty acids actually undergo β-oxidation.

Summary

A look at the fundamental processes in our bodies reveals the correct strategy for maximizing fat burning. It consists of what has been preached many times, yet is repeatedly interpreted differently. Without discipline regarding calorie intake and without physical activity, fat loss cannot be achieved permanently. If the first two points are met, then the use of specific fat-burning supplements also promises success—but only then.

Best regards

Yours,

Holger Gugg

www.body-coaches.de

Read also...

• 5 Golden Rules for Burning Fat
• Thyroid Hormone—The Metabolic Hormone—Part 1
• Thyroid Hormone—The Metabolic Hormone—Part 2

Source

Image - © F.Schmidt - Fotolia.com

“DSI Fact Sheet: Fat Digestion DE 2013” by Dr. Schär Institute - . Licensed under CC BY-SA 3.0 de via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:DSI_Infoblatt_Fettverdauung_DE_2013.jpg#mediaviewer/File:DSI_Infoblatt_Fettverdauung_DE_2013.jpg

Frank Boumphrey, M.D., 2009

http://www.bmj.com/content/349/bmj.g7257

Fundamentals of Biochemistry – Löffler, 7th Edition – Springer

The Effect of L-Carnitine on Fat Burning, the Respiratory Quotient, Body Composition, and Protein Turnover in Obese Adults – Andreas Popp – October 2010