FAT LOSS & Hormonal Adaptations
While adaptations to weight loss and low-calorie dieting happen on a grand scale, they also occur on the smallest cellular level.
During low-calorie dieting and weight loss, the body adapts by increasing mitochondrial efficiency so that you’re able to produce more energy and less waste from the food you eat.
Like I said before, efficiency is the curse of fat loss. Your cells’ mitochondria can pump out more ATP energy with less input.
On a Cellular level Part of this may be explained by the reduction in uncoupling proteins from weight loss.*1 Uncoupling proteins reduce the efficiency of ATP production in the mitochondria and cause extra energy to be given off as heat.
Thus these uncoupling proteins are very thermogenic. From an evolutionary perspective, it makes sense that these adaptive thermogenic proteins are “turned off” during weight loss as part of the body’s self-defense system—so that you don’t waste energy when food is scarce.*2
It’s been demonstrated that a greater decrease in the expression of uncoupling proteins in skeletal muscle is associated with greater metabolic slowing during weight loss.*3
20,000 years ago, these people would have been genetic ideals because they could resist famine much more effectively due to their superior metabolic self-defense system.
In today’s world, however, they are people who have a much more difficult time losing body fat.
Hormonal Adaptations
The endocrine system is also a target for metabolic adaptation. Most scientists agree that fat loss typically occurs not through a reduction in fat cell (adipocyte) numbers, but in fat cell size.
As fat cells shrink from weight loss, they reduce their secretion of a hormone called leptin.*4 Leptin is a major control hormone for hunger, metabolic rate, and many other metabolic outcomes.
It’s often viewed as a central control hormone for fat loss and fat gain. When you reduce your calories and drop your body fat levels, the shrinking fat cells reduce their leptin output.
Leptin not only responds to the long-term changes in fat cell size but also short-term energy flux across the adipocyte. That is, fat cells can be smaller in size, but short-term overfeeding can increase leptin—but more on this later when I talk about preventing body fat regain.
Interestingly, several studies have demonstrated that leptin levels are reduced to a greater extent than would be predicted by the amount of fat loss that occurs, even after weight has stabilized.*5*6*7*8
This is consistent with the data cited previously demonstrating that caloric restriction causes metabolic slowing to a greater proportion than the amount of fat that is lost.
Not only that, eating at a deficit and losing fat lowers the output of thyroid hormone (T3) and raises thyroid-stimulating hormone (TSH), which also contributes to a lower metabolic rate. *9
Furthermore, energy-restricted weight loss is also accompanied by reduced sympathetic nervous system (fight/flight) tone.*10
While the previously mentioned hormones fall, the hormone ghrelin increases as a result of the deficit and weight loss.*11
Increased ghrelin contributes to an increase in appetite with weight loss. There’s a reason it has the nickname “the hunger hormone.”
The increase in ghrelin and decrease in leptin could explain why dieting becomes progressively more difficult. Together they cause hunger levels to rise and make it more difficult to feel satiated.
These aren’t the only hormones that change during caloric restriction and may affect metabolic rate. Other hormones that have less of an effect on metabolic rate like testosterone, estrogen, and other sex hormones also change during a caloric deficit.*12
Interestingly, cortisol concentrations have been observed to significantly increase during caloric restriction.*13
These hormonal adaptations only examine the energy expenditure side of the equation.
Remember energy balance is calories in versus calories out. Not only is your self-defense system activating metabolic adaptations to slow down the metabolic rate, thus decreasing energy expenditure, but it’s also altering the milieu of hormones that impact satiety.
Hormones like PYY, CCK, and GLP-1 are anorexigenic (aka anti-hunger) hormones that increase satiety.*14*15*16. All of these hormones are reduced to a significant extent during energy restriction.*17*18*19
On the other hand, (orexigenic) Hunger hormones like ghrelin and orexigenic peptides such as neuropeptide-Y and Agouti-related peptides in the brain are significantly elevated during caloric restriction.*20*21
This reduction in total daily energy expenditure combined with an increase in hunger and decrease in satiety form the ‘energy gap’ proposed by MacLean et al., where more energy is desired than is required in response to caloric restriction and weight loss.*22
It’s worth mentioning that insulin levels decline during caloric restriction.*23 As fat cells shrink, they become more insulin sensitive, and thus less insulin is required to dispose of glucose and drive fats into adipose. This is a good thing from a health perspective, but a terrible thing from weight regain perspective.
You see, small, insulin-sensitive adipocytes also typically secrete low amounts of leptin, which makes them extremely efficient at the storage of fats. Think of adipocytes as sponges. If a sponge is soaking wet, you can’t then use it to soak up anything else (in this case large, insulin-insensitive fat cells).
If you wring out that same sponge as much as you can, then it becomes extremely efficient at soaking up liquid (small, insulin-sensitive fat cells). Further insulin and leptin both circulate in the body in proportion to fat mass and bind to receptors in the brain that increase the expression of anorexigenic peptides and decrease the expression of the orexigenic peptides.
This is part of the second prong of the body’s self-defense system, which prepares your body for regaining body fat even before you’ve finished your diet!
Decreased Energy Expenditure During Refeeding
Not only do hormonal adaptations to dieting increase your propensity to regain body fat, but other aspects of metabolic adaptation activate during dieting that predisposes your body to regain body fat once you finish dieting.
Possibly the most powerful adaptation is the increased efficiency of refeeding during caloric restriction.*24 You see, when you diet and impose an energy gap, the body becomes more efficient at using energy during the restriction—which we’ve hammered home repeatedly.
But research has also shown that when you increase food intake above maintenance after you’ve been dieting, your body more efficiently stores it as fat compared to weight- and LBM(lean body muscle)-matched controls.*25 Not only that, but it appears that both LBM and body fat are regained differentially from where it was lost.
Research has demonstrated that as weight is regained in the post-diet period, fat is preferentially stored in the trunk, and LBM is preferentially regained in the extremities first (meaning the trunk regains its LBM last).*26. This is significant because it appears that LBM in the trunk has a greater effect on metabolic rate compared to LBM in the extremities.*27
How does all of this affect our bottom line? Let’s look at a hypothetical example of two genetically identical people.
Person A goes on a diet for a month and loses weight and body fat, while Person B eats at maintenance calories. After one month, let’s assume both people are at the same weight and body fat level (meaning Person A had to lose body fat to reach Person B’s level).
If you challenge both of them with a high-calorie day that is the same relative increase in calories, Person A will store significantly more body fat than Person B due to the increased refeeding efficiency.
while person B is more likely to waste some of that energy through thermogenesis. We’ve heard people say, “You aren’t going to gain fat from one bad meal.” Usually, this is said in an effort to comfort someone who might have fallen off the wagon.
While it’s praiseworthy and possibly even necessary, depending upon that person’s psychological makeup, it’s certainly not true. I wish we could say that it’s impossible to gain fat from overeating at one meal, but that would be a lie, and not consistent with the scientific data or what we know about the body’s self-defense system.
On the contrary, your body’s self-defense system is designed to do exactly that! Ensure that you can store energy when you come across a surplus of food; it’s almost literally written in our DNA.
*1 Decreased mitochondrial proton leak and reduced expression … – NCBI. Retrieved January 3, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/12145158
*2 (2014, February 27). Metabolic adaptation to weight loss: implications for the … – NCBI – NIH. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943438/
3 (2018, May 17). Response of skeletal muscle UCP2-expression during metabolic …. Retrieved September 11, 2018, from https://www.nature.com/articles/s41366-018-0085-2
4 Biology’s response to dieting: the impetus for weight regain. – NCBI – NIH. Retrieved January 3, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/21677272
5 (2016, May 2). Persistent metabolic adaptation 6 years after “The Biggest Loser …. Retrieved January 3, 2018, from http://onlinelibrary.wiley.com/doi/10.1002/oby.21538/full
6 (2018, September 23). Metabolic adaptation to caloric restriction and subsequent … – NCBI. Retrieved November 27, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/26399868
7 (n.d.). Sixteen years and counting: an update on leptin in energy balance.. Retrieved November 27, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/21633176
8 (n.d.). Basal metabolic rate in anorexia nervosa: relation to body composition …. Retrieved November 27, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/10837290
9 Moderate weight loss is sufficient to affect thyroid hormone – NCBI – NIH. Retrieved January 3, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/23902316
10 Baseline sympathetic nervous system activity predicts dietary weight …. Retrieved January 3, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/22090279
11 Weight loss increases circulating levels of ghrelin in human obesity.. Retrieved January 3, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/11874411
12 (2012, October 31). Sex hormone changes during weight loss and maintenance in …. Retrieved January 3, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635052/
13 (2017, August 3). Case Study: Unfavorable But Transient Physiological Changes During …. Retrieved January 3, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/28770669
14 (n.d.). The satiety hormone peptide YY as a regulator of appetite. – NCBI. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/18441153
15 (2016, November 16). Cholecystokinin-induced satiety, a key gut … – NCBI – NIH. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485878/
16 (n.d.). Effects of GLP-1 on appetite and weight – NCBI – NIH. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119845/
17 (n.d.). Peptide YY levels are decreased by fasting and elevated … – NCBI – NIH. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/16362815
18 (n.d.). Effect of weight loss and ketosis on postprandial cholecystokinin and …. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/18469245
19 (2017, May 6). Attenuating the Biologic Drive for Weight Regain Following … – NCBI. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/28481261
20 (2017, May 6). Attenuating the Biologic Drive for Weight Regain Following … – NCBI. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/28481261
21 (n.d.). Twenty-four-hour ghrelin is elevated after calorie restriction and …. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/17299118
22 (n.d.). Biology’s response to dieting: the impetus for weight regain. – NCBI – NIH. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/21677272
23 (n.d.). Biology’s response to dieting: the impetus for weight regain. – NCBI – NIH. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/21677272
24 (2014, February 27). Metabolic adaptation to weight loss: implications for the athlete. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943438/
25 (n.d.). Adaptive changes in energy expenditure during refeeding … – NCBI. Retrieved September 11, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/2393003
26(2018, April 5). How dieting makes some fatter: from a perspective of human … – NCBI. Retrieved November 7, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/22475574
27 (2018, April 5). How dieting makes some fatter: from a perspective of human … – NCBI. Retrieved November 7, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/22475574
