How to Increase the 3 Major Steps of the Fat Loss Process

by Mike Mutzel


Fat Loss Demystified

The terms “fat burning,” “melting fat,” and “getting shredded” are pretty unempirical, but vivid! One scientific way to describe fat burning is mitochondrial beta-oxidation. In brief, this process describes how stored and dietary lipids are oxidized (burned) inside a mini-cellular organ called the mitochondria. As an aside, about 10% of your body weight is mitochondria, the majority of which is found inside muscle tissue. This is one reason why maintaining high levels of muscle mass through regular and high-intensity weight training (even for women) is essential to keeping the pounds off! Muscle is where fat is burned—the more muscle you have, the more efficient you’ll burn fat.

Since fat burning during exercise can increase lipid flux by up to 65 percent, this discussion will focus on fatty acid oxidation inside muscle tissue during exercise. Although we do burn some stored lipids for energy during day-to-day activities and at rest, exercise is required to burn significant amounts of fat. Additionally, a recent study found that exercise, not calorie restriction, leads to the greatest reduction in fat (triglycerides) in circulation.[1]

Fatty Acid Lipolysis: Chopping up Fats to Be Burned in Muscle Mitochondria
Both stored and dietary fats (triglycerides) need to be converted into free fatty acids (FFA) before they can be burned as fuel in the mitochondria. This is through a pathway called lipolysis, which literally translates as “lipid splitting.” Although lipolysis occurs in all tissues and cell types, the biochemical pathway is most active in fat tissue and to a lesser extent inside muscle tissue.

During exercise, free fatty acids make their way to the mitochondria to be burned. They come from three main sources: stored fat in adipocytes (fat cells), circulating cholesterol molecules (lipoprotein particles, including VLDL and LDL, which shuttle dietary fats around the body), and stored fat inside muscle tissue (intramyocellular lipid). Let’s hone in on how stored fat is liberated from fat cells and then is burned to fuel exercising muscle.

How fat is lost via lipolysis with mike mutzel

The surface of adipocytes (fat cells) contains two lipolytic enzymes that split stored triglycerides into free fatty acids: adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). Insulin and the catecholamines adrenaline and noradrenaline are the two major signaling molecules that regulate lipolysis of ATGL and HSL (freeing stored fats from fat cells). When catecholamines latch onto the adrenergic receptor, they subsequently activate the HSL and split the stored triglycerides into free fatty acids, which are then mobilized by way of the capillary network to the exercising muscle.

the major steps of fat burning lipolysis
Duncan, R. E., Ahmadian, M., Jaworski, K., Sarkadi-Nagy, E., & Sul, H. S. (2007). Regulation of Lipolysis in Adipocytes. Annual Review of Nutrition, 27(1), 79–101. doi:10.1146/annurev.nutr.27.061406.093734

How Adrenaline and Caffeine Work to Increase Fatty Acid Oxidation

During exercise, levels of adrenaline rise dramatically and spark the lipolysis complex to efficiently break up stored lipids—at the level of both the fat cells and the muscle tissues. Roughly 70 to 80 percent of the lipids liberated by adrenaline are burned as fuel. (So by just dragging your butt to the gym and getting your heart rate up, you will burn fat!)

Caffeine has been shown to increase the rate of lipolysis by more than twofold, and it works synergistically with adrenaline to increase lipolysis and promote fatty acid oxidation.[2] Increased fat loss during exercise is not the only favorable effect attributed to caffeine; the substance has also been shown to make exercise more enjoyable and less difficult.[3]

Alcohol and Beta-Blockers Can Make You Fat

Stimulation of the adrenergic receptor is key to activating the fat-loss process. Since beta-blockers block adrenergic receptors, it should not be surprising that their use is linked with weight gain, reduced energy expenditure, and whole-body thermogenesis.[4] Use of these blood pressure medications is also linked with poor exercise tolerance, insulin resistance, and increased blood lipid levels.

Alcohol also decreases adrenergic receptor stimulation, so it too decreases lipolysis and whole-body fatty acid oxidation.[5] So, it’s best to limit alcohol intake and especially avoid alcohol within the two-hour post-workout window, as these enzymes are still functioning and you don’t want impair them.

Delivering Fatty Acids to the Muscle

Low-to-moderate intensity exercise optimally delivers these newly cleaved fatty acids (from lipolysis) to the skeletal muscle. It’s been thought that super-high intensity exercise can actually reduce blood flow around fat tissue, reducing fatty acid transport to muscle.[6] So, for optimal fat loss, medium-intensity aerobic training might be best.

Fatty Acid Oxidation Inside the Mitochondria

Maintaining a high-level of lean muscle mass and regular exercise are the best ways to keep your cellular powerhouses, the mitochondria, burning fatty acids. A study of endurance athletes, for example, found that the athletes had a 54 percent increase in energy use in their mitochondria compared to their sedentary counterparts. Exercise increases two key signaling molecules, AMPK and PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), both of which stimulate the mitochondria to burn fat and sugar more efficiently. When increased by fasting, exercise, cold temperatures, and certain natural compounds, the AMPK and PGC-1α pair also instruct the mitochondria to divide, a process known as mitochondrial biogenesis. In sum, these molecular switches guide or instruct mitochondria to “burn, baby, burn,” instead of “store, baby, store”!

Learn the strategies to turn your gut bacteria into fat-burning machines
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Natural Ways to Increase AMPK and PGC-1α

A plethora of nutrients, herbs, and botanicals have been shown to increase AMPK signaling, optimizing mitochondrial function and fat and sugar burning. Alpha-lipoic acid (ALA) in particular has been shown to increase AMPK signaling and fat burning in humans. Italian researchers instructed 1,127 overweight subjects to take 800 mg of ALA daily for four months.[7] At the end of the study, participants reported a nine percent reduction in body mass, along with significant reductions in blood pressure and belly fat, compared to baseline. Korean researchers followed a similar approach; but instead, they cranked up the dose to 1,800 mg ALA daily for four months.[8] Compared to the placebo group, high-dose overweight individuals lost significantly more belly fat and body weight.

In addition to ALA, some of the best nutrients known to increase AMPK and maximize our body’s fat-burning capabilities are berberine, butyric acid, capsaicin (from chili peppers), chromium, curcumin, EGCG (green tea polyphenols), genistein (soy), ginseng (Panax quinquefolius), quercetin, and resveratrol.

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Omega-3 Fatty Acids Increase Lipolysis

In a terminator-like fashion, omega-3 fatty acids and their metabolites reverse the buildup of toxic lipid metabolites (lipotoxicity) in muscle, the liver, and the pancreas. One study showed that 500 mg of DHA a day for six months improved fatty liver in children with liver disease.[9]

In a recent 12-week study, fish oil proved to be friendly to muscle and a foe to fat. Researchers in Australia gave overweight people 1.9 grams of omega-3 fatty acids a day and instructed them to exercise three days a week for 45 minutes. The placebo group still exercised but took sunflower capsules instead of fish oil. Fish oil users burned more fat as a result of exercising while maintaining lean muscle mass compared to subjects who did not take fish oil. This muscle-sparing effect is critical, as lean muscle is the site of mitochondrial fat-burning.

Nearly all of these studies hint at the positive cardiovascular effects offered by fish oil through significant reductions in blood triglycerides and small dense LDL particles. An easy way to increase your EPA and DHA levels to eat three, 3-oz servings of wild-caught salmon, sardines, mackerel, or herring weekly. Avoid farm-raised fish altogether and when dining out, skip the Atlantic salmon, as that is farm-raised too. Increasing fish intake to this level equates to roughly 400 mg EPA and DHA a day. To speed up fat loss, improve lean muscle mass, reduce blood triglycerides, and decrease inflammation, take 1,500-2,000 mg of combined EPA and DHA each day with meals.

L-Carnitine Can Help Shuttle Fat Acids into the Mitochondria

The free fatty acids formed from lipolysis can only be shuttled into the mitochondria through a transporter molecule called L-carnitine, which is why some people promote L-carnitine for fat loss. It’s not a great fat loss agent by itself, but when combined with caffeine, green tea, and exercise, L-carnitine can help speed things along. Some studies suggest that fatty acid transport during exercise is limited by L-carnitine availability. I suggest 1,000-2,000 mg of L-carnitine tartrate first thing in the morning before aerobic exercise.


1) Gill, J. M., & Hardman, A. E. (2000). Postprandial lipemia: effects of exercise and restriction of energy intake compared. Am J Clin Nutr, 71(2), 465–471.

2) Groop, L. C., Bonadonna, R. C., Shank, M., Petrides, A. S., & DeFronzo, R. A. (1991). Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man. J of Clin Invest, 87(1), 83–89. doi:10.1172/JCI115005

3) Schubert, M. M., Hall, S., Leveritt, M., Grant, G., Sabapathy, S., & Desbrow, B. (2014). Caffeine consumption around an exercise bout: effects on energy expenditure, energy intake, and exercise enjoyment. J Appl Physiol, 117(7), 745–754. doi:10.1152/japplphysiol.00570.2014

4) Sharma, A. M., Pischon, T., Hardt, S., Kunz, I., & Luft, F. C. (2001). Hypothesis: Adrenergic receptor blockers and weight gain: a systematic analysis. Hypertens, 37(2), 250–254. doi:10.1161/01.HYP.37.2.250

5) Siler SQ, Neese RA, Hellerstein MK. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am J Clin Nutr 1999;70:928–36.

6) Bülow, J., & Madsen, J. (1981). Influence of blood flow on fatty acid mobilization from lipolytically active adipose tissue. Pflügers Archiv – European J Physiol, 390(2), 169–174. doi:10.1007/BF00590202

7) Koh, E. H., Lee, W. J., Lee, S. A., Kim, E. H., Cho, E. H., Jeong, E., et al. (2011). Effects of alpha-lipoic acid on body weight in obese subjects. Am J Med, 124(1), 85.e1–85.e8. doi:10.1016/j.amjmed.2010.08.005

8) Carbonelli, M. G., Di Renzo, L., Bigioni, M., Di Daniele, N., De Lorenzo, A., & Fusco, M. A. (2010). Alpha-lipoic acid supplementation: a tool for obesity therapy? Curr Pharm Des, 16(7), 840–846.

9) Kabir, M., Skurnik, G., Naour, N., Pechtner, V., Meugnier, E., Rome, S., et al. (2007). Treatment for 2 mo with n−3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr, 86(6), 1670–1679.

10) Flachs, P., Rossmeisl, M., Bryhn, M., & Kopecky, J. (2009). Cellular and molecular effects of n−3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clin Sci, 116(1), 1. doi:10.1042/CS20070456


Join the conversation

  1. Mike, Is it true that you need to do some slow cardio after HIIT or strength training to burn off the free fatty acids that are released into the blood stream during these workouts, to avoid them being restored? Thanks! Kate

    • Hi there Kate,

      Great question. About 80% of the FFA raised from lipolysis are utilized for beta oxidation; it's a pretty efficient process. The body has a nice way of matching lipolysis with energetic demands, so I don't think you're going to "re-gain weight" or have issues from doing the exercise.

      Moreover, you become a more efficient fat burner through regular exercise; so don't worry too much about cardio after. (A little cool down might not hurt though.)

  2. I have the same question as Kate. Doing some cardio after HIIT or strength training to burn free fatty acids is being touted by some as the best way to get rid of the fatty acids. Otherwise they risk being stored back into fat cells. Just wandering your thoughts on this subject.


    • Hi Dawn,

      Probably not a big concern. The equilibrium to match lipolysis with beta-oxidation is pretty tight.

      Super high intensity exercise actually shuts down lipolysis, as the body shifts more into sugar-burning mode.

      Hope this helps,


  3. Is it better to do cardio first thing in the am when I wake up or do it later in the morning like before lunch?

    • Hi there Sherry,

      I think if fat loss is a primary goal, first thing in the morning would be best.

      Before lunch is better than nothing, but you'll get most ROI from first morning fasted cardio.



  4. Hello Mike,

    I'm confused. You wrote: "So, for optimal fat loss, medium-intensity aerobic training might be best." But in your book, Belly Fat, you discuss the 3 pillars re: mitochondria rejuvination, and seem to indicate that high speed intensity works best. I'm trying to follow your 3 pillar approach, as a diabetic, doing brief intensity on a recumbent bike, but would like for you to elaborate on what appears to be a contradictory "best" approach, if you don't mind. Thanks!

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