LPL – An Important Key of the Metabolic Equation of Fat

LPL - Lipoprotein Lipase

Introduction

Lipoprotein lipase (LPL) is an enzyme playing an important role in lipid metabolism. Its purpose is to facilitate the transport of fatty acids inside the cells throughout your body, such as muscle, adipose, and heart tissue to name a few.

What does it do?

Say you eat a meal that has some fat in it. Once the fatty acids get into your intestines, they are packaged into chylomicrons (a lipoprotein) as triglycerides and they are transported to different parts of the body, such as: to the liver, to the cardiac tissue, to muscle tissue, to adipocytes, etc.

Before going further I would like to emphasize on the fact that I think there is not one single enzyme or hormone that should be considered decisive by itself, but that things should always be put into perspective so that the bigger picture is visible. I discuss about LPL, leptin, grehlin, insulin and other factors of this equation in the upcoming book (see the end of the article).

 Chylomicrons and LPL

Chylomicron

This is where LPL gets into the scene. Its role is to unload (remove) the fat from these chylomicrons and from VLDL (very low density lipoprotein which carries cholesterol and fat from the liver to tissues) and use the fat for energy usage such as oxidation by the muscles or for storage into the adipose tissues. It is important to say that LPL works aside with the Apolipoproteins from the chylomicrons in their job to hydrolyze and remove fats from TAG [3].

Atherogenic and LPL

We would want to have, as Peter Attia says, more LPL activated on muscle tissue so that fat oxidation is enhanced and less LPL activated on adipose tissue so that fat storage is minimized. But there are several factors that impact LPL activity.

Insulin and LPL

According to Michael King [3] LPL synthesis is regulated, in part, by insulin. It has been shown that insulin activates LPL in adipocytes and this promotes the uptake of fatty acids in the adipose tissue and it decreases LPL expression on muscle cells, which means less oxidation of fat by muscle. Read this study to see more about it [4].

A very recent study that came out a few days ago gives in-depth insight into the physiological regulation of LPL [5]. It refers to the regulation of LPL in adipocytes, in the muscles, in the heart, and in other tissues and it also discusses about the proteins that play an important role in its modulation.

An older and quite interesting study conducted on 28 elder males provides insight about LPL activity in the muscle and how it is related to insulin sensitivity [6].

Another source of thorough information with regards to insulin and the lipogenic process is here [8]. The article describes how insulin exerts its on LPL effects by stimulating its formation with the end goal of having TAG hydrolyzed so that FFA (free fatty acids) would enter the adipocytes.

Dietary Macronutrients, Fasting and LPL

In this study [9] researchers wanted to determine how different dietary macronutrients impact LPL activity (both in the fat tissue and in the muscle tissue) as well as insulin sensitivity.

25 normal weight subjects were assigned into either a high-fat diet group or a high-carb diet group. Their experiment lasted for 16 days. I find the study non-conclusive on the high-fat diet part because these subjects were fed: 30% carbohydrate from the total caloric intake, 50% fat, and 20% protein. We know that according to Phinney and Volek high fat diets should be higher in fat (at least 60%) and very low in carbohydrates (<10%).

I’d be interested in seeing how LPL is activated in both muscle and adipose tissue when subjects follow a high-fat-very-low-carb diet.

The closest that I could get to was a study showing how fasting activates LPL in muscle and down-regulates LPL in adipose tissue. Immediately after eating, the opposite occurs as LPL is down-regulated on muscle tissue and up-regulated on adipose tissue.

However, I’d also be interested in seeing how different meals (in terms of macronutrients) have an impact on LPL activity. I would test the assumption “different macronutrients => different LPL activity”.

Must read this one [10] and this one [11]. These studies also talk about cold thermogenesis and LPL activity that is stimulated in brown adipose tissue.

This is a validation for what we know about fasting and how LPL is down-regulated in adipose tissue and up-regulated in muscle tissue. The up-regulation of LPL on muscle tissue during fasting for the purpose of fat oxidation makes me think of the sparring effect on protein breakdown during fasting.

It seems that the muscle prefers using fat and not breakdown protein from the muscles for gluconeogenesis. I will dig more into this.

Circadian Cycle and LPL

When reading about the circadian cycle the first thing that comes to my mind is Jack Kruse. He’d definitely wanna read this study if he didn’t do it so far [12].

It seems that LPL gene [13], the gene that provides the instructions to make the enzyme LPL, is triggered in liver at night. A mice study [12] ( I hate mice studies) shows how two-fold up-regulation of LPL at night leads to higher fatty acid oxidation in the muscle and can contribute to fat overload (I believe they refer to over-eating fat).

A good point of the study is that circadian disruption (messed-up sleep-awake cycle) can lead to imbalance in LPL gene expression which can be a potential cause of the metabolic syndrome.

What happens when LPL is Deficient

Changes caused by mutations in the LPL gene [13] usually lead to familial LPL deficiency where fatty acids cannot be removed from Chylomicrons and VLDL. This means that more TAGs circulate through the blood, stomach pain is present and subjects often develop pancreatitis (inflammation of the pancreas) and enlargement of the spleen and the liver [14].

Other changes in the LPL gene expression may have an important role in understanding atherosclerosis because excess fatty acids in the blood (that cannot be removed from their carrier proteins) may accumulate in the arterial wall as a result of inflammation [13].

Take Away

This may tend to be a bit sciency but some key points are:

– LPL is found to be activated on many tissues throughout the body, such as muscle, heart, and adipose tissues.
– LPL is influenced by insulin secretion, among others. Higher insulin => higher LPL activity on adipose tissue => accumulation of fat in adipocytes. So, keep insulin low.
– LPL is influenced by dietary intake, fasting, and cold thermogenesis. Fasting promotes LPL activity on muscle cells, thus oxidation of fat by the muscle.
– LPL gene expression and LPL enzyme activity can be influenced by the circadian cycle.
– LPL gene mutations lead to familial LPL deficiency and can contribute to diabetes, obesity, the metabolic syndrome, as well as atherosclerosis.

It’s amazing how this small enzyme can play such an important role in the bigger metabolic equation. What are your thoughts on this?

Resources:

1. Attie, A. D. (2007). High-maintenance proteins and hypertriglyceridemia. Nature genetics, 39(12), 1424-1425.

2. Santa Monica College – Cholesterol, Phospholipids, Triglycerides, and Lipoproteins.

3. King, M. (2014). Lipoproteins. The Medical Biochemistry Page.

4. Kiens, B., Lithell, H., Mikines, K. J., & Richter, E. A. (1989). Effects of insulin and exercise on muscle lipoprotein lipase activity in man and its relation to insulin action. Journal of Clinical Investigation, 84(4), 1124.

5. Kersten, S. (2014). Physiological regulation of lipoprotein lipase. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids.

6. Pollare, T., Vessby, B., & Lithell, H. (1991). Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. Arteriosclerosis, thrombosis, and vascular biology, 11(5), 1192-1203.

7. International Chair on Cardiometabolic Risk – Photo

8. Albright, A.L. and Stern, J.S. (1998). Adipose tissue. In: Encyclopedia of Sports Medicine and Science, T.D.Fahey (Editor). Internet Society for Sport Science.

9. Yost, T. J., Jensen, D. R., Haugen, B. R., & Eckel, R. H. (1998). Effect of dietary macronutrient composition on tissue-specific lipoprotein lipase activity and insulin action in normal-weight subjects. The American journal of clinical nutrition, 68(2), 296-302.

10. Braun, J. E., & Severson, D. L. (1992). Regulation of the synthesis, processing and translocation of lipoprotein lipase. Biochemical Journal, 287(Pt 2), 337.

11. Mead, J. R., Irvine, S. A., & Ramji, D. P. (2002). Lipoprotein lipase: structure, function, regulation, and role in disease. Journal of Molecular Medicine, 80(12), 753-769.

12. Delezie, J., Dumont, S., Dardente, H., Oudart, H., Gréchez-Cassiau, A., Klosen, P., … & Challet, E. (2012). The nuclear receptor REV-ERBα is required for the daily balance of carbohydrate and lipid metabolism. The FASEB Journal, 26(8), 3321-3335.

13. National Institute of Health (2008). LPL.

14. National Institute of Health (2008). Familial Lipoprotein Lipase Deficiency.

15. Dr. Stephen Phinney and Dr. Jeff Volek (2011). The Art and Science of Low-Carbohydrate Living.

16. Dr. Jack Kruse (2013). Epi-paleo Rx: The Prescription for Disease Reversal and Optimal Health

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