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Know Your Lipid Metabolism

Know Your Lipid Metabolism

There are various reasons to know about lipid metabolism. One of them is to understand how the stored fat in your body is burned to provide you the energy to get through your day. Higher lipid metabolisms give you a better edge in making use of the stored body fat while lower lipid metabolism does the opposite. Facing challenges with losing weight? It may be due to your lipid metabolism!

What are lipids and how does it affect your body?

Lipid or better known as fatty acids are long-chain organic acids with the general formula of CH3(CnHx)COOH. Lipids can be saturated or unsaturated. Saturated fat is considered unhealthy as it is claimed to raise your cholesterol levels which contribute to heart diseases. Unsaturated lipids, on the other hand, has lesser energy than saturated lipid but are as essential in the storage of fat in the body. However, too much-unsaturated lipids post its own challenges as it makes your body more vulnerable towards peroxidation. Fortunately for us, there is a way to solve that issue, which is by the use of antioxidants.

Lipid metabolism process

Lipid metabolism is the process of synthesizing your fat store for energy. These fats are first obtained by consuming food and absorbing them. This process applies to plants but for plants, the process differs.

Endogenous pathway of lipid metabolism

VLDL (very-low-density lipoprotein) synthesized by the liver and released into the systemic circulation. In the tissues, LPL (lipoprotein lipase) cleaves TAGs from the VLDL to release fatty acids that are taken up by myocytes for energy or by adipose tissue for storage. As LPL cleaves TAGs, the cholesterol concentration within the lipoprotein increases and becomes a smaller, denser lipoprotein named “intermediate-density lipoproteins” (IDL)—the action of LPL may continue to form LDL (low-density lipoproteins), a smaller denser particle than IDL.

To sum it up, the endogenous pathway is related to the role of LPL in cleaving VLDL to form IDLs, taken up by the liver or LDLs and FFAs.

Exogenous pathway of lipid metabolism

This is when the dietary fat and cholesterol comes into the picture. It is absorbed by the duodenum and proximal jejunum to generate chylomicrons which is secreted at the lateral borders of enterocytes and enter mesenteric lymphatics and later will be accessing the plasma via the thoracic acid and are rapidly metabolized by LPL to yield chylomicron remnants. These remnant receptors (LRP1/HSPG) and LDL receptors are taken up in the liver. Free fatty acids liberated by the action of LPL are available to adipose for storage and to other tissues (e.g., skeletal muscle, heart) for use as energy substrates. To put it into simpler words, the exogenous pathway reflects on an action of lipoprotein lipase (LPL) on chylomicrons to form free fatty acids (FFAs).

Where does lipid metabolism occur?

Since lipids (fats) are hydrophobic, hydrolysis in lipid metabolism occurs in the cytoplasm which ends up creating glycerol and fatty acids.

What is the role of the liver?

Aspects of lipid metabolism are predominantly carried out by the liver. Here are the few roles that the liver does to support fat metabolism:

  • The liver is extremely active in oxidizing triglycerides to produce energy. The liver breaks down many more fatty acids that the hepatocytes need, and exports large quantities of acetoacetate into the blood where it can be picked up and readily metabolized by other tissues.
  • A bulk of the lipoproteins are synthesized in the liver.
  • The liver is the major site for converting excess carbohydrates and proteins into fatty acids and triglycerides, which are later exported and stored in adipose tissues.
  • The liver synthesizes large quantities of cholesterol and phospholipids. Some of this is packaged with lipoproteins and made available to the rest of the body. The remainder is excreted in bile as cholesterol or after conversion to bile acids.

What is abnormal lipid metabolism?

Lipids are fats or fat-like substances. It includes oils, fatty acids, waxes, and cholesterol. Any abnormalities in your lipid metabolism mean you may not possess enough enzymes to break down lipids. Or the enzymes are not working properly and your body is unable to convert the fats into energy. This will cause a harmful amount of lipids to build up within your body. Over time, cells and tissue damage occur, especially in the brain, peripheral nervous system, liver, spleen, and bone marrow. Many of these disorders are serious and sometimes fatal.

These disorders are usually inherited. Newborn babies get screened using blood tests to check if they are diagnosed with the disorder. If there is a family history of one of these disorders, parents are advised to conduct genetic testing to verify if they are carrying the gene. Meanwhile, some other genetic tests can tell whether the fetus has the disorder or carries the gene for the disorder.

Lipid storage disease

It is a group of inherited metabolic disorders in which harmful amounts of fatty materials (lipids) accumulate in various tissues and cells in the body.  Lipids are important parts of the myelin sheath that coats and protects the nerves but over time, this excessive storage of fats can cause permanent damage to cells and tissues in the brain, peripheral nervous system, as well as in other parts of the body.  The symptoms may appear early in life or develop in the teen or adult years. Affected individuals face complications with the lack of muscle coordination, brain degeneration, feeding and swallowing difficulties, slurred speech or increased sensitivity to touch.

Acid Lipase Disease

This disease occurs when the enzyme needed to break down certain fats that are normally digested by the body is lacking or missing. As a result, a toxic build-up of these fats is stored in the body’s cells and tissues. Two rare and inherited lipid storage diseases are caused by the deficiency of the enzyme lysosomal acid lipase. It affects both males and females. In certain cases, the infants with the disorder would appear normal at birth but quickly develop progressive mental deterioration, low muscle tone, enlarged liver and grossly enlarged as they grew older.

Barth Syndrome

Barth syndrome (BTHS) is a rare genetic disorder of lipid metabolism that usually affects males. It is caused by a mutation in the tafazzin gene (TAZ, also called G4.5) which leads to decreased production of an enzyme needed to produce cardiolipin. Cardiolipin is an essential lipid that is important in energy metabolism. What BTHS does to the body is it triggers varying degrees of heart muscle weakness (cardiomyopathy), neutropenia (low white blood cell count which may lead to an increased risk for bacterial infections), reduced muscle tone (hypotonia), muscle weakness, undeveloped skeletal muscles, delayed growth, fatigue, varying degrees of physical disability, and methylglutaconic aciduria . This unique disease are linked from mother to son through the X chromosome. Only boys will develop the symptom. Daughters to an affected male would be a carrier but luckily would not be affected.

Fabry disease

It is a deficiency caused by the lack of a faulty enzyme needed to metabolize lipids, fat-like substances that include oils, waxes, and fatty acids. The mutated gene allows lipids to build up to a serious level of harmful in the autonomic nervous system (which controls involuntary functions such as breathing and digestion), cardiovascular system, eyes, and kidneys.

Farber’s disease

Also known as Farber’s lipogranulomatosis. A lipid storage disease with difficulty in having excess amounts of lipids build-up to harm the joints, tissues, and central nervous system. The liver, heart, and kidneys also may be affected. This symptom typically appears during early infancy but some may occur later in life. The most common symptom includes moderately impaired mental ability and difficulty with swallowing. Some people may even need a breathing tube. The severe case related to this disease is when both parents are carrying the disease and passed them along to the next generation. This is a concern disorder because it affects both males and females.

Effect of insulin resistance on lipid metabolism

Insulin resistance has been recognized as an important and independent risk factor for the development of type 2 diabetes and cardiovascular diseases. This understanding has evolved over the last two or three decades, first in close relation with obesity and later on, also in the non-obese populations. Frequently, insulin resistance appears in the non-diabetic population together with a cluster of risk factors including high blood pressure, chronic low-grade inflammation, and hyperlipidemia, which characterize the metabolic syndrome. The most common and typical disorders of lipid metabolism in these cases are, indeed, the high triglyceride and low HDL levels, a combination that has long been described as responsible for the high risk of cardiovascular events.
The physiological mechanisms for the association of hypertriglyceridemia, low LDL levels, and insulin resistance are becoming increasingly clear. Apart from the well-discussed influence of insulin resistance on the activity of lipoprotein lipase, it seems that hyperlipidemia per se might be, conversely, a promoter of systemic inflammation, a cornerstone of the metabolic syndrome.
In the meantime, it is worthwhile to focus attention on patients with high triglyceride and low HDL-cholesterol levels, even in the absence of obesity. They could be possible candidates for a detailed investigation of the carbohydrate metabolism, or more specifically, viewed as patients at high risk for the development of diabetes and cardiovascular complications.

Treatment options for poor lipid metabolism and fat reduction in the body

Currently, there is no specific treatment available for most of the lipid storage diseases. Enzyme replacement therapy is available for Gaucher and Fabry diseases. The U.S. Food and Drug Administration has approved migalastat (Galafold) as an oral drug to treat adults with Fabry disease who have a certain genetic mutation. Antiplatelet drugs used to treat stroke can slow the decline of kidney function seen in Fabry disease.  Medications may be prescribed to help treat pain.

Enzyme replacement therapies can help with a few of these disorders. For others, there is no treatment. Medicines, blood transfusions, and other procedures may help with complications.

Practical clinical approach

The treatment strategy depends predominantly on the overall cardiovascular risk and the severity of lipid metabolism disorder. Since these disorders are considered above all from the viewpoint of primary and secondary prevention of atherosclerosis, it is advisable to focus on patients who are at high or very high risk of cardiovascular events and lower their LDL cholesterol accordingly.

Exclusion of secondary lipid metabolism disorders

A number of diseases can have the consequence of secondary lipid metabolism disorders. Clinically, the most important of these are diabetes mellitus (hypertriglyceridemia or mixed hyperlipoproteinemia), hypothyroidism (LDL hypercholesterolemia), kidney diseases (hypertriglyceridemia, mixed hyperlipoproteinemia, lipoprotein(a) elevation), and cholestatic liver diseases (apparent LDL cholesterol elevation). Disorders of lipid metabolism are also observed in the context of other diseases (e.g., lymphoma, Cushing syndrome, and porphyria). When the lipid metabolism disorder is a secondary manifestation, treatment should be focused primarily on the underlying disease. Patients with diabetes mellitus or kidney disease often form exceptions to this rule, because optimal regulation or elimination of the underlying disease is not achieved and they show aspects of both primary and secondary lipid metabolism disorders.

Lifestyle modification

Lifestyle modification plays a significant role in the treatment of lipid metabolism disorders. The greatest effect is achieved by decreasing the intake of saturated fatty acids, i.e., particularly animal fats. The impact of orally consumed cholesterol is minor so that the new recommendations in the USA dispense entirely with advising restriction of cholesterol intake. Lifestyle modification has a considerably greater effect in hypertriglyceridemia, alone or in combination with changes in the concentrations of other lipids. Strict limitation of alcohol consumption and reduction in the intake of rapidly resorbed carbohydrates sometimes lower the triglyceride level by >50%. Physical activity also improves the lipid profile.

Even though the effect on lipid concentrations is limited in some cases, modifications of lifestyle can have a favorable impact on the risk profile. For example, a Mediterranean diet with additional olive oil or nuts leads to a 30% reduction of relative risk in high-risk patients. Interestingly, eating nuts also leads to a lowering of LDL cholesterol, so it can be debated whether at least part of the risk reduction is determined by a favorable influence on the lipid profile.

LDL hypercholesterolemia

The European guidelines recommend that the target concentration for LDL cholesterol should depend on the overall risk. If this goal is not reached by lifestyle modification alone, the administration of a statin represents the first step in medicinal treatment. If the target LDL cholesterol level has still not been attained after 4 to 6 weeks of treatment, the dose should be adjusted accordingly. In high-risk patients, lifestyle modification measures and statin treatment should be initiated simultaneously.
Initial studies have shown that very early high-dose statin administration improves the prognosis of patients with ACS (acute coronary syndrome). The most plausible explanation is a direct improvement of endothelial function, independent of LDL cholesterol. Meanwhile, however, these results are being interpreted more cautiously. Nevertheless, most guidelines recommend starting with high-dose statin treatment in patients with ACS.

Mixed hyperlipoproteinemia

Owing to its close association with the metabolic syndrome, mixed hyperlipoproteinemia, in which the concentrations of both LDL cholesterol and triglycerides are raised, is the most frequently occurring disorder of lipid metabolism in diabetics. Here too, the primary treatment goal is regulation of the LDL cholesterol level. To this end, a statin is prescribed, perhaps in combination with ezetimibe. With regard to the hypertriglyceridemia, modification of the patient’s lifestyle is the key measure. If this combination of lifestyle modification and statin treatment does not achieve the target concentrations or at least normalize the triglyceride level, combined medicinal treatment can be considered.

In principle, a statin can be administered together with omega-3 fatty acids or fibrates, but both of these combinations have performed disappointingly in endpoint studies. Because these studies were poorly designed, however, no definitive conclusion can be drawn. In the absence of comparative studies, neither of these two treatments can be preferred to the other. It may be best to test both combinations and then continue with the one that is tolerated better and achieves a superior response.

Conclusion/ Final Thoughts

In conclusion, lipids (fats and complex molecules that the body needs to break down in order to utilize and derive energy from) are absorbed from the intestine and undergo digestion and metabolism before they can be utilized by the body.
We have discussed the complications of impaired digestion of fats and lipid metabolism above, the diseases associated with the process and how they affects the quality of life. There isn’t a cure currently and the best options available now are long term medication and lifestyle changes.

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