🌎 Spend £75 For Free Worldwide Shipping

The Science Behind Fat Loss

by Chris Spearman

There is no shortcut to success in any walk of life and fat loss is no different. Too often are we bombarded with fad diets with no real scientific backing and no real substance. Fat loss isn’t really that difficult and often the problem in the media is that it is over complicated with too many variables.


To investigate fat loss in some depth we will need to put our biochemistry hats on for a short while. A relevant quote from Phil Learney that always springs to mind; “Nutrition is just an applied form of biochemistry,” and sometimes we do really need to break it down and go back to the fundamentals to look at things at a molecular level. Even after a 4 year Biochemistry BSc. degree, a Molecular Cell Biology MSc. and my current PhD research I need to refresh my knowledge on cellular biology, which isn’t always straight forward: never ending molecular pathways, downstream signaling, antagonistic ligands, auto-regulation, receptor modification, truncating proteins etc. a never ending mine field of cellular mechanics. Here we will just touch on a few topics, looking at some key hormones and how they play a critical role in relation to stubborn fat that might enable us to become more educated towards tackling the issue.



Insulin is paramount when we talk about burning fat. Insulin takes charge of managing our hormonal state and part of our natural fluctuation between a state of regeneration and degeneration. Genetics and individual hormonal balance affects how well insulin is managed in the body at a basal level, however our environment and diet can influence this even further. Being able to regulate and manage insulin requires stabilizing blood sugar levels due to the level of carbohydrates in our diet.


Insulin is a fat storing hormone. Isn’t it? Pick up any biochemistry textbook, and you will learn about two enzymes responsible for fat gain or fat loss, lipoprotein lipase (LPL) and hormone sensitive lipase (HSL). LPL is associated with fat tissue and activated by insulin. LPL works by stripping fatty acids from a triglyceride (a glycerol molecule carrying three fatty acids) and therefore allowing fatty acids to be stored as fat around the body. It is well documented that insulin also suppresses HSL. HSL on the other hand does the exact opposite: HSL strips fatty acids from these triglycerides, enabling them to be burned as energy. In essence: insulin is a “storing and locking hormone.” It can store fat, and if it is present it reduces fat release.


This is exactly why even when on a low calorie diet, for people who are extremely insulin resistant, it can cause havoc, often causing a loss of muscle tissue instead of fat, excessive weight rebound, insatiable cravings and hunger. Note: even after insulin affects the freeing up of fat cells, once the fat arrives at the cell to be burned insulin also interrupts the rate limiting step (RLS) in fat burning, an enzyme called carnitine palmitoyltransferase I (CPT-1).


It seems pretty clear how paramount insulin metabolism in terms of fat storage. How this happens as we’ve seen can happen in a number of ways: did you eat yourself into insulin dysfunction? Did you stress yourself there? Is it a combination of both? Truth be told, it’s actually FAR more complex than this, once we add hungry hormones, inflammatory compounds and brain chemistry into the mix but taking care of insulin should be top of our priority.


A schematic showing insulin’s affect on adipose tissue receptors due to the presence of high glucose in the blood stream (Bodybuilding.com).



Cortisol is a bit more difficult and probably the most widely misunderstood hormone in the human body. Cortisol also blocks LPL but stimulates HSL. So contrary to what people think, cortisol can also be a fat burning hormone as well as a fat storing hormone. Which of these pathways predominates the other is determined by other hormonal influences and that is the take away point here.


For example: cortisol with a high level of growth hormone and testosterone (endogenous or exogenous) results in fat burning where as cortisol with insulin primarily results in fat storing. Notably: cortisol interrupts our insulin metabolism actually causing the body to make even more insulin, thus creating a vicious cycle of high insulin and high cortisol. Needless to say this is a recipe for disaster for anyone looking to get lean.


Thyroid Hormone:

As most of us already know, thyroid hormones are critical in the regulation of our Basal Metabolic Rate (BMR). Therefore, if we look at the average western diet of 3 large meals with the biggest meal generally being the evening meal, it is extremely likely that this person will over eat when trying to meet calorific requirements. If they do not meet calorific requirements, however, what generally happens here is that Leptin will decrease as Ghrelin (appetite stimulating hormone), Anandamine and Neuropeptide-Y increases. The result of all of these hormonal changes results in: irritable hunger, struggle to lose body fat AND on a low calorie diet. In summary: muscle will be used, as fuel so weight WILL come down to a point).


Naturally the physiological response every time someone over eats: thyroid hormones raise metabolic rate, which causes heat generation. For those of us who regulates metabolic rate successfully, overeating will lead to a notable increase in body temp. IF however, this isn’t you, and then perhaps the timing of a cheat meal isn’t appropriate? For most of us, continuous binging and/or overeating will eventually lead to the burnout of the thyroid hormones. This is once again an indication of under activity within these hormones.


Note: overeating is NOT total calories it is in fact calories “per meal”. Contrary to a lot of flexibly dieting beliefs, 3,000kcal is NOT JUST 3,000kcal. It is important how it is dispersed and often the reason why putting clients on diets that exceed their previous calorific intake BUT increasing the amount of meals will often led to fat loss. The timing of these macronutrients, and the combinations of these in EACH meal is essential too but that enters into the topic of nutrient timing, best left for another day.



What is leptin? Leptin is a hormone secreted from fat tissue that plays an integral part in the regulation of hunger and feelings of satiety. Like all hormones, leptin has a wide variety of functions, however its primary function and most relevant to us is its role in regulating fat-cell size (1). The mechanism of action is: following the release of leptin from fat cells, a signal is sent to the brain to reassure the body that adequate food has been received and it is now time to but the knife and fork down (2,3). For this reason, leptin is extremely important in the regulation of fat loss albeit indirectly. Four key factors that regulate leptin levels include:


  1. Fasting:

Although is seems pretty straight forward, how often do we hear: “I was so busy I had no time to eat” or “I was so busy I didn’t have time for breakfast”? Usually followed by: “I’m so hungry I could eat the house”. This leaves you in a state of starvation, which causes havoc with your leptin levels. Periods of fasting is thought to activate a survival mechanism that down regulates leptin levels and increases the hormone responsible for feeling hungry: ghrelin (1,6). Leptin levels in extreme cases can become clinically suppressed, although it is unclear how long this takes, it is very likely that those with extremely low percentages of body fat consuming extremely low and reduced-calorie-diets are experiencing notable decreases in leptin concentrations.


  1. Exercise:

We all know that exercise burns calories and overtime this may lead to weight loss and body fat store reductions. However, most of us don’t take into account that overall body mass including fat tissue impacts total daily energy expenditure, believe it or not. In fact, specific studies have shown significant reductions in basal metabolic rate following fat loss. Therefore, whilst losing weight I fantastic for our physiques, it can have a negative impact on leptin levels AND metabolism (7).


  1. Body Composition:

As we have mentioned, fat cells secret leptin, therefore the lower our percentage of body-fat is, the less of this appetite-suppressing hormone gets secreted (2,10,11). Importantly people with a higher body-fat percentage generally have elevated leptin concentrations, which researchers expect is due to leptin resistance (10,12,13). This insensitivity is caused by the brain becoming insensitive to the hormone itself, and therefore drastically reduces its ability to affect hunger and satiety.


  1. Overfeeding:

Overfeeding also effects leptin concentration in the body. Although overfeeding does elicit a change in leptin levels, not all macronutrients have the same response. For example: fat has virtually no effect on leptin concentrations, believe it or not and even reduces leptin levels in some cases (14,15,16). Contrary to fats, carbohydrates (as would be expected) have a positive affect on leptin (15,17,18). It is though that high-glycemic carbs may be the sole reason for increases in leptin (19). Leptin doesn’t increase immediately after a meal per se, instead the increase in leptin levels are anywhere from 4-48 hours after carbohydrate refeeding (1,17,20). It’s important at note at this point that overdosing on protein doesn’t directly affect leptin levels.

Leptin’s effect on the hypothalamus and its subsequent effect on hunger and satiety.

When To Cheat:

There is NO exact science for having a “cheat meal” but I do follow quite a number of general rules for myself and my clients with regards to cheat meals:


  • If your body fat is in excess of 25% it is extremely rare that I will allow cheat meals! Generally because someone at this level of body fat WILL make conscious and unconscious mistakes with regards how they plan a cheat meal as a general rule. Not only this but it is very unlikely that they need or will benefit physically from a cheat meal and unless a person is considerably lean then there is little or no physiological benefit to having a cheat meal.


  • For clients whose body fat ranges generally between 15-25%, I will issue a cheat meal every 2-3 weeks depending on psychological factors around their nutrition although this is probably not hugely necessary, more so from a psychological approach.


  • >10% I would use a ‘re-feed’ or cheat meal every week depending on how they are reacting to each cheat meal. Very often, clients will benefit hugely from a “re-feed’ or a cheat meal at this point and often can help push pass fat loss plateaus leading up to photoshoots and competitions.


  • It is almost a rule for my clients to try and train a weak body part before their cheat meals. Naturally this helps grow lagging areas whilst dropping bodyfat even in the later stages of a diet.


  • My clients will always follow up their “Cheat Day” with a low/no carb day. This is a great way to boost your metabolism and add that extra edge to carb cycling.


  • I find it crucial to do cardio the day following a “Cheat Day”. Metabolism goes into over-drive, so taking full advantage of this is paramount.


What Do I Consider a Cheat?

A cheat meal simply has to be an excess of calories and a substantial elevation in carbohydrates if we want to spark up a metabolic response and affect the hormones mentioned above.


NOTE: a cheat meal does not necessarily mean eat rubbish! More often than not it will be far more beneficial to have a clean re-feed. These re-feeds will have an extremely high percentage of carbohydrates in them and generally if I have a high carbohydrate meal then fats are low. Perfect example would be: 500g white potato and 150g of steak spaced 3-4 times throughout the day generally in and around my workout that day.


Within 24-48 hours post re-feed, your body will turn into a metabolic furnace. You will become visibly leaner as the calories are now being burned at an exponential rate before it begins to ease off. Make the most of this change in metabolism is key, although it may be tough, I make sure to increase cardio in the 48 hours after my re-feed along with a drop in calories (carbohydrates).

Put Simply:

To cut subcutaneous (body) fat effectively with minimal muscle loss there are a few things to consider and prioritize:


  • Create a deficit of total calories through either a reduction in dietary calories or an increase in fuel (calorie) usage.
  • Increase or stabilize anabolic hormones and decrease catabolic hormones as much as possible.
  • Increase or maintain protein and nutrient turnover.
  • Increase the overall metabolic output of the body.
  • Strategically and periodically increase leptin levels and thyroid output with the integration of cheat meals and/or re-feeds where applicable.



As we have seen from the ACTUAL science behind fat loss, there s a lot more to great conditioning than simply being in a calorie deficit. There are a whole array of hormones, proteins and cellular mechanisms to think about that work synergistically to help us achieve our goals when aiming for the perfect physique. Although these are all hugely important don’t make the mistake of thinking that reading a mound of scientific papers will get you lean, it wont. You still need to go out and get the work done, you still need to burn those calories, activate those pathways and stimulate those muscles fibers. Work hard, keep learning, stay educated and the results will follow.  



  • Weigle, D. S., Duell, P. B., Connor, W. E., Steiner, R. A., Soules, M. R., & Kuijper, J. L. (1997). Effect of Fasting, Refeeding, and Dietary Fat Restriction on Plasma Leptin Levels 1. The Journal of Clinical Endocrinology & Metabolism, 82(2), 561-565.
  • Jørgensen, J. O., Vahl, N., Dall, R., & Christiansen, J. S. (1998). Resting metabolic rate in healthy adults: relation to growth hormone status and leptin levels. Metabolism, 47(9), 1134-1139.
  • Jeon, J. Y., Steadward, R. D., Wheeler, G. D., Bell, G., McCargar, L., & Harber, V. (2003). Intact sympathetic nervous system is required for leptin effects on resting metabolic rate in people with spinal cord injury. The Journal of Clinical Endocrinology & Metabolism, 88(1), 402-407.
  • Levine, J. A., Eberhardt, N. L., & Jensen, M. D. (1999). Leptin Responses to Overfeeding: Relationship with Body Fat and Nonexercise Activity Thermogenesis 1. The Journal of Clinical Endocrinology & Metabolism, 84(8), 2751-2754.
  • Roberts, S. B., Nicholson, M., Staten, M., Dallal, G. E., Sawaya, A. L., Heyman, M. B., ... & Greenberg, A. S. (1997). Relationship between circulating leptin and energy expenditure in adult men and women aged 18 years to 81 years. Obesity Research, 5(5), 459-463.
  • Klok, M. D., Jakobsdottir, S., & Drent, M. L. (2007). The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obesity Reviews, 8(1), 21-34.
  • Leibel, R. L., Rosenbaum, M., & Hirsch, J. (1995). Changes in energy expenditure resulting from altered body weight. New England Journal of Medicine, 332(10), 621-628.
  • Doucet, E., Imbeault, P., St-Pierre, S., Almeras, N., Mauriege, P., Despres, J. P., ... & Tremblay, A. (2003). Greater than predicted decrease in energy expenditure during exercise after body weight loss in obese men. Clinical Science, 105(1), 89-96.
  • Goldsmith, R., Joanisse, D. R., Gallagher, D., Pavlovich, K., Shamoon, E., Leibel, R. L., & Rosenbaum, M. (2010). Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 298(1), R79-R88.
  • Sinha, M. K., Opentanova, I., Ohannesian, J. P., Kolaczynski, J. W., Heiman, M. L., Hale, J., ... & Caro, J. F. (1996). Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. Journal of Clinical Investigation, 98(6), 1277.
  • Lammert, O., Grunnet, N., Faber, P., Bjørnsbo, K. S., Dich, J., Larsen, L. O., ... & Quistorff, B. (2000). Effects of isoenergetic overfeeding of either carbohydrate or fat in young men. British Journal of Nutrition, 84(02), 233-245.
  • Heymsfield, S. B., Greenberg, A. S., Fujioka, K., Dixon, R. M., Kushner, R., Hunt, T., ... & McCamish, M. (1999). Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA, 282(16), 1568-1575.
  • Hukshorn, C. J., Saris, W. H., Westerterp-Plantenga, M. S., Farid, A. R., Smith, F. J., & Campfield, L. A. (2000). Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. The Journal of Clinical Endocrinology & Metabolism, 85(11), 4003-4009.
  • Horton, T. J., Drougas, H., Brachey, A., Reed, G. W., Peters, J. C., & Hill, J. O. (1995). Fat and carbohydrate overfeeding in humans: different effects on energy storage. The American Journal of Clinical Nutrition, 62(1), 19-29.
  • Dirlewanger, M., Di Vetta, V., Guenat, E., Battilana, P., Seematter, G., Schneiter, P., ... & Tappy, L. (2000). Effects of short-term carbohydrate or fat overfeeding on energy expenditure and plasma leptin concentrations in healthy female subjects. International Journal of Obesity, 24(11), 1413-1418.
  • Havel, P. J., Townsend, R., Chaump, L., & Teff, K. (1999). High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes, 48(2), 334-341.
  • Romon, M., Lebel, P., Velly, C., Marecaux, N., Fruchart, J. C., & Dallongeville, J. (1999). Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake. American Journal of Physiology-Endocrinology And Metabolism, 277(5), E855-E861.
  • Hagobian, T. A., Sharoff, C. G., & Braun, B. (2008). Effects of short-term exercise and energy surplus on hormones related to regulation of energy balance. Metabolism, 57(3), 393-398.
  • Herrmann, T. S., Bean, M. L., Black, T. M., Wang, P., & Coleman, R. A. (2001). High glycemic index carbohydrate diet alters the diurnal rhythm of leptin but not insulin concentrations. Experimental Biology and Medicine, 226(11), 1037-1044.
  • Kolaczynski, J. W., Nyce, M. R., Considine, R. V., Boden, G., Nolan, J. J., Henry, R., ... & Caro, J. F. (1996). Acute and chronic effect of insulin on leptin production in humans: studies in vivo and in vitro. Diabetes, 45(5), 699-701.


Leave a comment

Please note, comments must be approved before they are published

5-Star Rated Leggings
Free Worldwide Shipping Available
30-Day Money Back Guarantee
Always Helpful Customer Support