Hormones and weight loss: An in depth review
Introduction
Energy homeostasis: The biological functions that attempt to balance calories in vs calories out
Energy homeostasis is a complex process which is minutely adjusted second by second through both voluntary actions (such as eating food), and involuntary actions (such as hormone secretion).
Two hormones in particular, leptin and ghrelin, seem to be the most influential in regulating appetite and as a result, our ability to control our body weight.
Why is it so hard to lose weight?
The laws of thermodynamics means that energy can’t be created out of thin air, we need to be consistently eating more calories than we burn to gain weight and burn more calories than we eat to lose weight (ideally from our fat and not muscle). As simple a formula as it might be on paper, calories in - calories out, anyone who has tried to lose a significant or consistent amount of weight will attest that weight loss can be a difficult and lengthy process, so why is that?
As it turns out, our bodies don’t like change and will try their hardest to influence things to remain the same, and this is what we call 'energy homeostasis'. The aims of effectively reducing hunger and increasing satiety (fullness) have been driving obesity researchers mad for years as they attempt to unlock our gastrointestinal secrets. If we could properly regulate hunger and satiety, we could make obesity a rarity rather than the norm. What makes it so tricky is appetite, hunger and satiety are all influenced by dozens of interacting hormones. Coordinating all this hormonal ruckus is the 'enteric nervous system', a subdivision of the autonomic nervous system that directly controls the gastrointestinal system.
With gut hormones discovered only a century ago, and gut peptides becoming an increasingly important focus in obesity research just within the last decade, it has only recently grown apparent how seemingly innocuous hormones have a significant role in regulating energy intake.
This article will look at the two big players of those hormones; leptin, and ghrelin.
Ghrelin
Ghrelin, also known as lenomorelin, is a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract. If you want a hormone in particular to blame for all the times you've found your stomach rumbling with hunger, its ghrelin. Known as an orexic hormone, ghrelin is an appetite-stimulating hormone and a potent one at that. A good way to remember it is to think, if your stomach's growlin, it's probably ghrelin. When food enters, causing the stomach to stretch ghrelin is absorbed, and when the stomach is empty ghrelin is secreted.
Not just a hunger hormone
According to ongoing research, ghrelin has multiple biological roles: for example, ghrelin stimulates the release of growth hormone and also induces a rise in the concentration of other hormones including cortisol. Through these multiple mechanisms, ghrelin can accelerate food intake boosting weight.
Ghrelin also plays a vital role in regulating reward perception through activation of the cholinergic-dopaminergic reward link, a system that communicates the hedonic and reinforcing aspects of natural rewards such as food, and addictive drugs such as alcohol. In general terms, this means that if you block ghrelin's influence in the brain, the pleasure derived from eating and certain drugs is also blocked. This isn't just hypothesised, having already been tested as a treatment for alcoholism with significantly successful trials.
Leptin
Back in 1994, researchers noticed that one genetically altered strain of mouse ate significantly more than other mice and was obese. When researchers administered a new substance, leptin (from leptos, or “thin” in Greek), the mice lost weight. Soon after, nearly everybody interested in fat research was researching leptin. At the time this was the 'holy grail' of obesity research: a protein that made obese mice into skinny mice? Fantastic! We’ll just make leptin pills, and everyone will be ripped, including the mice. Unfortunately, like with most things in biology, the oft-repeated phrase of “I think you'll find its a bit more complicated than that” applies. As it turns out, leptin injections only worked on people (and mice) who were genetically leptin-deficient — only about 5-10% of obese subjects. The remaining 90-95% were out of luck. So what does this mean and what does leptin actually do?
In contrast to ghrelins orexic effects, leptin is an anorexic, or appetite diminishing, hormone, and due to this, ghrelin and leptin are in a constant battle over your hunger levels. Leptin is primarily made by adipose cells, and its primary function is to regulate fat stores through controlling satiety. Before the discovery of leptin, adipose tissue was thought to only be an inert energy storage organ, rather than the active endocrine organ it was found to be. So what factors control your levels of leptin?
Leptin is controlled primarily by two things, which are:
Short term:
Acute energy balance. A severe caloric deficit causes leptin levels to drop lower than can be explained by the loss of fat, and caloric surpluses raise leptin levels higher than what can be explained by fat gain.
Long term:
Total amount of adipose tissue. Leptin production occurs within adipocytes (individual fat cells), and as such higher amounts of fat mass causes increased levels of leptin production, conversely meaning that lower levels of body fat reduce the absolute amount of circulating leptin.
Metabolic slowdown
Researchers have known for years of a phenomenon called “metabolic adaption” or “adaptive thermogenesis”: As people lose weight, their BMR actually slow down to a greater degree than can be explained by mere weight loss.
To be clear: It isn’t surprising that as people lose weight, their metabolism slows down as well, after all, the less mass you have on your body, the fewer calories you need to expend it a day to maintain your body weight. What is surprising is that the metabolic slowdown during weight loss, and even after weight loss appears to be substantially higher than what fat/mass loss alone can explain. To explain why this happens we have to go deeper into what happens when you begin to lose weight.
Overeating and undereating very quickly cause a myriad of unconscious physiological responses, all designed to return you to your baseline. When you overeat the following day, your body compensates by having an increases body temperature, unconsciously fidgeting more and having a reduced appetite. This all sounds well and good, but the caveat is that the amount of energy burned by differs person to person, to a degree which is currently unclear. More research is showing that while these homeostatic controls are continually working to regulate energy balance, they are being overwhelmed in today's obesogenic environment and largely 'shut down' when chronic overeating occurs.
Set Point Theory
The Set Point Theory aims to explain why so many people rebound after massive amounts of weight loss. It proposes that every person has a ‘set point’ of which your body wants its weight to remain around, and when you deviate from that range, your body attempts to return to it through adaptive thermogenesis. Thankfully research is suggesting that you can change this range, albeit not necessarily in the right direction.
Once you gain weight and keep it on for a period, your body adjusts and can become accustomed to its new, larger size. It has become your ‘Set Point’ and when you deviate from this a number of subtle changes occur. Hormone levels change, adaptive thermogenesis occurs— slowing the resting metabolism, and as a result, leads to increased hunger and decreased satiety from food, all in a seeming conspiracy to get the body back to its set point weight.
Set points are different for every person, with estimates being that the average person has a set point range of about 5-10kg range in which your body won’t fight the changes
Science based methods for appetite suppression
Get enough sleep - Sleep deprivation raises cortisol levels and subsequent cravings for energy dense foods
Aim to get at least 8 hours of sleep at night, and if that’s impossible, taking naps during the day (and before 4pm) can help erase your sleep debt
Eat protein - Eating more protein, and eating it first has a significant suppression of appetite when compared with carbohydrates and fats
Eat fibrous foods
Eating low-calorie food that results in intestinal bulk is a good way to limit caloric intake while suppressing the urge to eat more.
While vegetables with a high water content will shrivel and shrink after consumption, foods high in soluble fiber will ‘gel’ and expand in the stomach.
Vegetables high in cellulose, an indigestible carbohydrate, will also result in increased intestinal bulk.
A low dose of a stimulant (such as caffeine) can help reduce hunger, but too much can result in nausea and other side effects.
Take away message
The people who have had success in losing weight have a few things in common:
They weigh themselves at least once a week.
They exercise regularly at varying degrees of intensity, with the most common exercise being walking.
They restrict their calorie intake, eat nutrient dense foods (vegetables, fruit etc), and get sufficient protein intake (aim for ~30g of protein with each meal)
Takeaway message
Obesity, fat loss and hormones are all incredibly complicated topics, all of which are far too complex to address in a single article, so by no means consider this the last word on this topic.