Lipotoxicity

Logan McFall,
Health Extension Agent,
Oconee County, Clemson University

HTF 1117

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Lipotoxicity is a rarely used term for a very common condition-one that affects more than 25% of the population. It is a type of metabolic syndrome (a combination of high blood pressure, high cholesterol and other lipids, insulin resistance and possibly obesity) and is a result of an overload of fatty acids (fat producers) in the body. Under normal circumstances, fatty acids are synthesized (processed) and transported in the blood stream only as needed for energy and normal bodily functions. Excess lipids are stored in adipose tissue, or fat, located around the body. Under “lipotoxic” conditions, lipids are synthesized and stored in areas that are not meant to hold fat, such as organs, especially around the abdomen. This fat storage can be “toxic” to organs, and thus lipotoxicity can result in heart disease, kidney disease, liver disease, and is closely related to diabetes. Fat stored outside of adipose tissue is known as visceral fat. Figure 1 below shows the storage of excess fats inside the body.

Some common areas in the body where free fatty acid store under lipotoxic conditions.

Some common areas in the body where free fatty acid store under lipotoxic conditions.
Gaggini et al, Hormone Molecular Biology and Clinical Investigation

Causes

Currently, there is no known cause of lipotoxicity. A genetic component has been studied, but no single gene was determined to cause the condition. There is debate in the medical community as to whether obesity prevents or causes lipotoxicity. An obese person may not be lipotoxic as his or her excess fatty acids could be stored correctly in adipose tissue, meaning the fat is not absorbed into organs. A lipotoxic person may not be obese as his or her excess fatty acids could be stored improperly outside of adipose tissue, meaning the fat the person does have is not stored in the proper places. Regardless, a diet high in saturated fat is more likely to cause lipotoxicity. Once adipose cells are “full” the excess lipids are stored elsewhere, causing other cells to “overeat” and store fat where they typically would not.

Prevention

The best way to prevent lipotoxicity is to avoid a diet high in saturated and trans fats. These fats are commonly found in non-lean animal products. Controlling cholesterol also lowers the risk for lipotoxicity. This involves lowering Low Density Lipoprotein (LDL) numbers and raising High Density Lipoprotein (HDL) numbers. This can be achieved in part by replacing saturated fats with healthier mono- and polyunsaturated fats commonly found in plant sources. Some examples of these healthy fats include avocados, olive oil, and coconut milk. Healthier fat options can be worked into the diet by replacing less healthy fat options, such as using olive oil mayonnaise rather than traditional egg based mayonnaise or replacing butter with a light avocado spread. Unhealthy fats can be avoided by consuming fewer animal fats and replacing them with leaner meat sources, such as fish or chicken, or even a lean beef rather than chuck. Maintaining a healthy weight and an active lifestyle helps prevent lipotoxicity, along with a myriad of other conditions, as fat chains are burned off as needed rather than lingering around in the body.

Symptoms

Lipotoxicity is a hard condition to detect because it has few symptoms in and of itself. Many of the symptoms of lipotoxicity are often related diseases: such as heart disease, obesity, diabetes, non-alcoholic fatty liver syndrome, and pancreas and kidney failure. Fatigue and exhaustion are also common under physical exertion for people with lipotoxicity.

Treatment

The best form of treatment is always lifestyle changes that you control yourself.  Replacing unhealthy fats with healthy ones actually has a beneficial effect and helps get rid of visceral fat (see prevention section above). Traditional treatments focus on removal of excess lipids from the body. The best way to do this can be overall weight loss, which means a combination of diet and exercise to remove adipose tissue as well as lipotoxic fats. The fastest way to burn fat is through strength training exercises, specifically those that engage the largest skeletal muscles in the body in the thighs. Always consult a doctor before beginning an exercise regimen with any preexisting conditions.

Because visceral or lipotoxic fat is harder to lose than normal adipose fat, sometimes a medication may be needed. The class of drugs known as thiazolidinediones for example, causes excess lipids to be absorbed into adipose tissue rather than the organs. Figure 2 shows changes in the body once this drug treatment begins. Another experimental treatment involves a drug that blocks the lipid uptake in muscle cells, thus shifting free lipids to adipose tissue for storage.

Related Conditions

Lipotoxicity is closely related with insulin resistance, which leads to diabetes. One of the areas free fatty acids often build up is in skeletal muscle. Muscle, due to its protein and water content, is polar, as is insulin. The lipids that take over muscle under lipotoxic conditions are non-polar, making it harder for insulin to be burned. Because the excess cannot be burned off as easily by skeletal movement, insulin resistance is increased, which raises the risk for Type 2 diabetes. The over accumulation of insulin and fat also increase weight gain and make it harder to lose weight.

Storage of Free Fatty Acids (FFA) and triglycerides (TG) before and after thiazolinedidiones (TZD)
Storage of Free Fatty Acids (FFA) and triglycerides (TG) before and after thiazolinedidiones (TZD)
DeFronzo et al, American Diabetes Association

Sources:

  1. Eldor, Roy, et al. “In Vivo Actions of Peroxisome Proliferator–Activated Receptors: Glycemic Control, Insulin Sensitivity, and Insulin Secretion.” Diabetes Care, American Diabetes Association, 1 Aug. 2013, care.diabetesjournals.org/content/36/Supplement_2/S162.
  2. Engin, A B. “What Is Lipotoxicity?” Advances in Experimental Medicine and Biology., U.S. National Library of Medicine, www.ncbi.nlm.nih.gov/pubmed/28585200.
  3. Gaggini, M, et al. “Not All Fats Are Created Equal: Adipose vs. Ectopic Fat, Implication in Cardiometabolic Diseases.” Hormone Molecular Biology and Clinical Investigation., U.S. National Library of Medicine, Apr. 2015, www.ncbi.nlm.nih.gov/pubmed/25816312.
  4. Kusminski, C M, et al. “Diabetes and Apoptosis: Lipotoxicity.” Apoptosis : an International Journal on Programmed Cell Death., U.S. National Library of Medicine, Dec. 2009, www.ncbi.nlm.nih.gov/pubmed/19421860.
  5. Schaffer, J E. “Lipotoxicity: When Tissues Overeat.” Current Opinion in Lipidology., U.S. National Library of Medicine, June 2003, www.ncbi.nlm.nih.gov/pubmed/12840659.

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