Leptin, ghrelin, and weight loss. Here’s what the research has to say. |

For the past few years, the research has been pretty clear on one thing: Leptin and ghrelin are big factors in appetite regulation. That’s why if you want to lose weight, you pretty much have to cut back on calories, reduce the fat in your diet, and increase exercise. But the relationship between those three things is not quite so straightforward. Since leptin and ghrelin are the two primary hormones that regulate appetite, it’s a little bit like finding the right key to open a lock.

While the exact role of leptin and ghrelin in weight regulation has been well-established, their mechanisms of action are still somewhat unclear. How do our fat cells know when we need to burn more calories? How do they sense when we’re full? And do they really control our hunger levels?

Leptin and ghrelin are hormones produced by our fat cells, and they play a role in regulating weight. Obesity researchers have found that people who have higher levels of leptin tend to be leaner, while those with higher levels of ghrelin tend to be heavier. You can see the effects of these hormones in the graphical representation below. The graph shows how leptin and ghrelin levels change with time in people who have lost weight. Some people are naturally more sensitive to these hormones, while others have low sensitivity and are less likely to lose weight.. Read more about leptin and ghrelin sleep and let us know what you think.

It’s a sobering statistic: the majority of individuals who embark on a diet and lose weight gain it back within a year.

That doesn’t seem encouraging.

What causes this to happen? There are many causes for this.

The main one is that many think of a “diet” as a temporary fix and don’t really alter their habits, which is why our Coaching program focuses on long-term transformation.

Another explanation is that our systems contain appetite- and weight-controlling hormonal processes that attempt to maintain homeostasis (i.e., the status quo) throughout time. Our bodies react by making us hungry when we regularly consume less energy (in the form of food) than we burn via basal metabolism and exercise (as in a diet or famine).

Our bodies, on the whole, are resistant to change. They want things to remain the same. When we attempt to alter something, our bodies react with compensatory strategies, such as increasing hunger hormones.

Leptin and ghrelin are two key hormones that influence our appetite and hunger signals. Let’s look at leptin, ghrelin, and weight reduction in more detail.

Appetite and body fat regulation by hormones

Leptin and ghrelin seem to be the main actors in hunger regulation, which affects body weight and fat. We tend to eat more when we are hungry. When we consume more, we either maintain our current weight or gain it again.

Leptin and ghrelin are both peripheral hormones that have central effects. To put it another way, they’re produced in other areas of the body (peripheral) yet have an impact on our brain (central).

Leptin is mainly produced in fat cells, although it is also produced in the stomach, heart, placenta, and skeletal muscle. Leptin is a hormone that reduces appetite.

Ghrelin is produced mainly in the stomach lining. Ghrelin makes you hungry.

Both hormones are affected by how well you’re nourished, and leptin is often linked to fat mass – the more fat you have, the more leptin you make. Your hypothalamus is activated by both hormones (a part of your brain about the size of an almond).

And here’s something more to consider: fat messes with both hormones and their messages.

Ghrelin and leptin act on the brain via the hypothalamus (from Kojima & Kangawa, 2006).

Leptin

Researchers discovered in 1994 that one genetically altered breed of mouse ate excessively and was fat. The mice lost weight after being given a novel chemical called leptin (from leptos, which means “thin” in Greek).

Almost everyone who was interested in fat research started looking at leptin soon after.

This was the golden grail of obesity research at the time: a protein that turned obese mice into thin mice. Fantastic! We’ll simply manufacture leptin tablets, and everyone, even the mice, will be ripped.

Leptin, like most things in biology, is a little more complex.

Leptin injections only worked on animals (and humans) who were genetically deficient in the hormone – only approximately 5-10% of fat individuals. The remaining 90-95 percent were unlucky.

How does leptin function?

Adipose tissue (fat) produces leptin, which is released into the circulatory system and transported to the brain. The hypothalamus is told by leptin that we have adequate fat and may eat less or cease eating. Although there is contradictory evidence on this, leptin may boost metabolism. (1)

The more fat you have, the more leptin you produce, the less food you will consume, and the greater your metabolic rate will be (possibly). The less fat you have, the less leptin you have, and the more hungry you will be.

Basically, the more leptin you have, the better.

Resistance to leptin

You’d think that if their leptin levels were high enough, obese people would suddenly stop eating or start losing weight. Unfortunately, you may develop a resistance to leptin (2).

You can have a lot of fat producing a lot of leptin in such scenario, but it won’t function. The brain is deafeningly deafeningly deafeningly dea There has been no decrease in appetite. There is no evidence of a faster metabolism. Your brain may even believe you’re hungry since there isn’t enough leptin in your system. As a result, you get even more hungry.

It’s a never-ending loop.

1. If you eat more, you’ll gain weight.
2. Greater leptin in fat cells equals more body fat.
3. When there is too much fat in the body, normal leptin signaling is disturbed.
4. You want to eat more because your brain believes you’re hungry.
5. You gain weight. And I’m getting hungry.
6. You consume more calories. More fat will be gained.
7. And so on.

Insulin resistance and leptin resistance are comparable (and they also share common signalling pathways). Insulin resistance develops when the body and brain generate a lot of insulin (for example, from a high-sugar, high-simple-carbohydrate diet), yet the body and brain no longer respond to insulin’s effects.

Both kinds of resistance seem to exist in obese individuals, but obese males with more internal belly fat (visceral fat) have higher insulin levels, whereas obese women with more fat beneath their skin have higher leptin levels (2).

Another interesting aspect about leptin resistance is that fructose seems to cause leptin resistance (3).

There are a few different theories on how leptin resistance works. Because there’s a buildup of leptin in the cerebral spinal fluid that bathes the brain, one hypothesis is that leptin can’t get to the hypothalamus because the proteins that transport it over the blood brain barrier aren’t functioning or aren’t present (4).

Regardless of the technicalities, the key point here is that having more body fat may mess with your hunger signals and actually make you hungry after a certain point.

Ghrelin

Ghrelin was discovered 7 years after leptin, although there was considerably less hoopla following the leptin letdown.

Leptin is a hormone that is produced as a consequence of fat accumulation and serves as a long-term weight regulator. In the meantime, ghrelin is the short-term solution. Hey, I’m hungry. When are we going to eat? regulator.

When your stomach is empty, it produces ghrelin. Ghrelin, like leptin, enters the bloodstream, passes the blood-brain barrier, and travels to the hypothalamus, where it signals hunger (1,5).

Ghrelin levels are high before meals and decrease thereafter.

You want less ghrelin if you want to reduce weight so you don’t feel hungry. If you want to gain weight, say if you’re underweight, you’ll want more ghrelin — or at the very least, you’ll want it to remain high while you eat, encouraging you to eat more.

As previously said, both hormones control appetite and hunger, as well as maintaining homeostasis – in this instance, keeping you well nourished. When you attempt to reduce weight, your body is likely to react by altering hormone levels, causing you to become more hungry.

This obviously poses a problem for those attempting to lose weight and keep it off, perhaps resulting to the infamous “yo-yo dieting” issue.

Question for investigation

Can the levels of leptin and ghrelin explain the ups and downs that dieters go through? Is it possible that this connection is more complex than we think?

The focus of this week’s analysis is on the relationship between leptin and ghrelin levels and weight regain after dieting. (The punch line is hinted at in the title.)

Crujeiras AB, Goyenechea E, Abete I, Lage M, Carreira MC, Martnez JA, Casanueva FF. Crujeiras AB, Goyenechea E, Abete I, Lage M, Carreira MC, Martnez JA, Casanueva FF. Higher baseline leptin and lower ghrelin plasma levels indicate weight return following a diet-induced loss. 2010 Nov;95(11):5037-44 in J Clin Endocrinol Metab. Epub 18 August 2010.

Methods

Over 160 obese and overweight men and women with an average BMI of over 31.1 kg/m2 were placed on a calorie restricted diet for eight weeks by researchers.

This diet provided 30 percent less calories (500-600 kcal/day) than the individuals’ total energy expenditure, with protein accounting for 15% of calories, fat for 30%, and carbs accounting for 55%. There was no change in physical activity, just a reduction in food intake.

The researchers took measurements of body weight, body fat, and waist circumference. Blood samples were also taken. Before dieting (week 0), immediately after dieting (week 8), and 6 months later, measurements were collected (32 weeks).

Results

People dropped an average of 5% body weight after 8 weeks on the diet. On average, males dropped 5.9% of their weight, while women lost 4.5 percent. They dropped 1.6 percent body fat and 4.1 cm off their waistlines on average.

There are winners and losers.

However, the average does not tell the full picture. Some people dropped over 5% of their body weight, while others lost less. This may seem self-evident and uninteresting… Until you examine their blood samples, that is.

Dieters who lost more weight (>5%) had a bigger drop in leptin and insulin compared to dieters who lost less weight (<5%). Somehow losing weight is correlated to drops in leptin and insulin.

Figure 1 below compares the differences between the two groups. Compared to the <5% weight loss group, the >5% weight loss group:

• additional weight loss (obviously)
• Having decreased amounts of leptin
• insulin levels were lower
• ghrelin levels were higher

Figure 1: Differences between >5% and <5% weight loss groups

This is basically what you’d anticipate.

This divide persisted six months after the diet stopped. Half of the group lost additional weight, while the other half gained back the weight they had lost.

Weight loss or increase was linked to blood levels of leptin and ghrelin, and the impact varied depending on sex.

• Women who had lower blood leptin levels at the conclusion of the diet were more likely to maintain their weight reduction, but ghrelin didn’t appear to matter.
• Men who had greater ghrelin levels at the conclusion of a diet were more likely to gain weight, but leptin didn’t appear to have a role.
• Insulin levels towards the conclusion of dieting didn’t appear to matter in the long run for both men and women, but insulin levels did rise when weight was regained.
• Ghrelin levels were greater (indicating they were hungry) towards the conclusion of dieting for both men and women, although ghrelin levels decreased in weight losers.

Huh.

Figure 2 depicts the differences in hormone levels between weight maintainers (WM) and weight regainers (WR) at the beginning of the diet (0 weeks), the conclusion of the diet (8 weeks), and six months afterwards (32 weeks). The red lines represent WRs, whereas the black lines with circles represent WMs.

Figure 2: Hormone levels in weight maintainers (WM) and weight regainers (WR), broken down by gender.

Conclusion and discussion

Weight regain is the most difficult obstacle for dieters to overcome, and coping with it is a tough task.

Appetite is influenced by a slew of interconnected variables. This research indicates that hormonal processes vary between men and women – and even between men and women.

This disparity may be due to the fact that men and women have distinct hormonal environments. Consider the following example:

• Ghrelin seems to be influenced by the secretion of growth hormone, which varies between men and women. (6)
• Leptin seems to have an effect on female reproductive and fertility, which is linked to body fat levels. Women seem to be considerably more sensitive to leptin levels than males… Unless estrogen is given to males. (6)
• Insulin delivered intranasally reduces hunger and weight loss in males, but increases hunger and weight gain in women… Unless the estrogen levels in women’s bodies or the testosterone levels in men’s bodies are low. (6)

There were, however, significant disparities within groups. While some guys lost weight, others gained it back. While some women lost weight, others gained it back.

These results indicate that “the presence of two distinct populations based on leptin and ghrelin levels [are] affecting the response outcomes,” as the researchers put it.

We’d anticipate those who gain weight quickly to have lower leptin levels and greater ghrelin levels, making them hungry. Our is not the case in this research. The findings “are consistent with a disturbance in the sensitivity to these hormone cues, presumably in the central nervous system of those individuals with a greater propensity to regain body weight,” according to the researchers.

This indicates that leptin and ghrelin signals may not always function as expected in obese individuals. Normal appetite signaling may be disrupted by obesity.

There’s definitely more to the tale, and additional study is needed to fully comprehend all aspects of weight reduction.

There are many variables that influence weight reduction.

As a result, it seems that a variety of key variables influence weight reduction success.

Give up now if you’re searching for the silver bullet that can suddenly eliminate hunger and reduce body fat.

Metabolic endocrinology seems to be no more difficult than combining a nuclear reactor with brain surgery. No one hormone regulates body composition, appetite, or hunger, and your hormonal profile may be very different.

Dieters who dropped the most weight on the diet also saw more substantial changes in their hunger. They were presumably more hungry when they were losing weight.

Does it make a difference what you eat?

The fact that this was a diet is one factor that is most certainly leading to weight gain. Reduce your calorie intake for eight weeks, reduce weight, and then hope for the best. Obviously, this approach has some value since it worked for some individuals.

Short-term diets, however, do not have a high long-term success rate, as shown by the statistics.

This diet’s macronutrient breakdown may also be important. It has a low protein content, a moderate fat content, and a high carbohydrate content. With a low-carb, high-fat, high-protein diet, for example, we may observe distinct hormonal impacts. (For additional information, see last week’s Research Review on high-protein diets.)

What other options do I have?

Taking fish oil and having regular sleep have been found to help improve ghrelin and leptin levels in certain studies. (7-9)

Other variables that contribute to long-term weight reduction are:

• physical activity has risen
• obtaining social assistance
• Techniques for changing behavior (for example, goal-setting) (10).

In conclusion

Our appetite and hunger are shaped by a complex network of hormones. These hormones and our responses to them are influenced by a number of variables.

So if you’re searching for a one-size-fits-all answer or depend on a quick-fix diet, you’re likely to be disappointed.

But there’s good news: there are a number of things you can take to alter your body composition permanently.

1. Take, for example, fish oil. Omega 3 fatty acids have been related to a reduction in appetite. (7)
2. Sleep. Sleep deprivation causes an increase in ghrelin and a decrease in leptin, as well as a disruption in glucose and insulin metabolism. (8,9)
3. These kind of research should not discourage you. Other studies suggests that losing weight and keeping it off is feasible if you do more than take a leptin tablet or perform a few jumping jacks. The National Weight Control Registry keeps track of what successful losers have in common. Changes in behavior, a dedication to healthy diet, and regular exercise are among them.
4. You should be aware that as you lose weight, you may get more hungry. That’s quite typical.
5. Become a member of the PN Coaching program. Thousands of people have relied on us to help them lose weight and keep it off for good. (And if you’re already doing Lean Eating, kudos!) You’ve come a long way!)

References

To see the information sources mentioned in this article, go here.

1. Drent ML, Klok MD, Jakobsdottir S. A overview of the function of leptin and ghrelin in the control of human food intake and body weight. 2007 Jan;8(1):21-34 in Obes Rev. Review.
2. Cell Metab. 2009 Jun;9(6):489-98. Woods SC. The regulation of food intake: behavioral vs molecular views. Review.
3. A. Shapiro, W. Mu, C. Roncal, K.Y. Cheng, R.J. Johnson, and P.J. Scarpace. Weight gain is exacerbated by fructose-induced leptin resistance in response to subsequent high-fat eating. 2008. 295 (5): R1370–5. Am. J. Physiol. Regul. Integr. Comp. Physiol.
4. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice, Münzberg H, Flier JS, Bjrbaek C. Endocrinology, 145(11), 4880-9, November 2004.
5. Ghrelin is an orexigenic and somatotrophic signal produced by the stomach, according to A. Inui. 2(8):551-60 in Nat Rev Neurosci, August 2001. Review.
6. Barkan, Ariel L., Eleni V. Dimaraki, Stacy K. Jessup, Kathleen V. Symons, Mikhail Ermolenko and Craig A. Jaffe. Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels. The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 5 2180-2184. doi:10.1210/jc.2002-021169
7. Beneficial effects of long-chain n-3 fatty acids incorporated in an energy-restricted diet on insulin resistance in overweight and obese European young people, Ramel A, Martinéz A, Kiely M, Morais G, Bandarra NM, Thorsdottir I. Epub 2008 May 20. Diabetologia. 2008 Jul;51(7):1261-8.
8. Pejovic S, Vgontzas AN, Basta M, Tsaoussoglou M, Zoumakis E, Vgontzas A, Bixler EO, Chrousos GP, Zoumakis E, Vgontzas A, Bixler EO, Chrousos GP. After one night of sleep deprivation, leptin and appetite levels in young healthy individuals were measured. 2010 Dec;19(4):552-8. J Sleep Res. 2010 Dec;19(4):552-8.
9. S. Taheri, L. Lin, D. Austin, T. Young, and E. Mignot. Short sleep duration is linked to lower leptin levels, higher ghrelin levels, and a higher BMI. PLoS Medicine 1(3):e62, 2004.
10. Greaves CJ, Sheppard KE, Abraham C, Hardeman W, Roden M, Evans PH, Schwarz P, Study Group TI. Greaves CJ, Sheppard KE, Abraham C, Hardeman W, Roden M, Evans PH, Schwarz P, Study Group TI. Systematic evaluation of reviews of intervention components linked to improved dietary and physical activity intervention efficacy. 2011 Feb 18;11(1):119 in BMC Public Health.
11. M. Kojima and K. Kangawa. Ghrelin’s functions and potential as a multitherapeutic hormone are discussed. 2006 Feb;2(2):80-8 in Nat Clin Pract Endocrinol Metab. Review.

Better eating, moving, and living.

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Frequently Asked Questions

How do you balance ghrelin and leptin?

Ghrelin is a hormone that stimulates hunger, while leptin is the hormone that suppresses hunger.

What is the role of leptin and ghrelin in weight management?

Leptin and ghrelin are hormones that control appetite.

What is the leptin method of weight loss?

The Leptin Method is a diet plan that has been around since the 1980s. It involves eating fewer calories and burning more calories in order to lose weight.

Related Tags

This article broadly covered the following related topics:

• leptin function
• leptin resistance
• leptin and ghrelin
• leptin
• leptin weight loss