Understanding Our Bodies: Leptin (The Fullness Hormone)

Time and time again, I tell you guys that the best way to stay healthy is to stay informed. Read labels, I say. Know what you’re eating. Know what you’re not eating. Know this, know that, etc and make informed decisions. Well, part of making informed decisions is understanding how your body works. And for that reason, I’ve decided to dive into a bit of physiology.

Even informed consumers tend to know very little about how their appetites actually work. What makes you hungry or full? Why do some foods fill us up more than others? What exactly is going on in our bodies, anyway?

I figured you just might want to know. So here is part one of a new series I call “Understanding Our Bodies” – nutrition based on how our bodies work. And to kick it off is a little explanation of the fullness hormone: Leptin.

What is Leptin?

Leptin is a hormone that is tied closely to regulating energy intake and expenditure, including appetite, metabolism and hunger. It is the single most important hormone when it comes to understanding why we feel hungry or full. When present in high levels, it signals to our brain that we’re full and can stop eating. When low, we feel hungry and crave food. It does this by stimulating receptors in our hypothalamus, the part of our brains which regulates the hormone system in our bodies. When leptin binds to receptors in this part of our brains, it stimulates the release of appetite-suppressing chemicals. People with leptin disorders eat uncontrollably.

 

Now here’s the strange part.  Leptin is produced mostly by our adipose tissue – aka our fat.  The level of circulating leptin is directly proportional to the total amount of fat in the body.  That means the more fat you have, the greater the amount of leptin you have. It may seem counter-intuitive, but it makes sense in the end when we consider how yo-yo dieting tends to be. It takes some time for your body to adjust to large changes in body fat levels when it comes to leptin.

So when you lose a lot of weight quick, via liposuction or serious calorie restriction, your leptin levels plummet. Subsequently, you get hungrier, your thyroid decreases output and your metabolic rate drops. Your body then increases catabolic hormone activity and appetite, making you tend to slip off your regime and gain all that weight right back. That’s why crash diets are often ineffective – your leptin won’t let you eat less, and even if you do, you’re lethargic and your metabolic rate slows way down.

Of course, just because it makes things difficult for dieting, leptin levels are far more sensitive to starvation than overeating. So when you cut caloires and start ot burn fat, the leptin levels in your body plummet, but when you eat too much they don’t skyrocket – although they do increase. Leptin levels increase with increased insulin levels, like right after eat, and when our body is storing energy. Keeping this in mind, in general, can help you eat healthier and loser weight in the long run.

The Science of Leptin

Obviously, since leptin is so key to hunger and feeling full, scientists have been looking into it as a possible target for anti-obesity or weight loss. As it turns out, leptin controls a lot more than just our feelings of fullness.

Turning on leptin in the brains of mice causes them to exercise more, according to research from Harvard Medical School. It’s interwoven into how our bodies control our metabolism, activity levels, and energy budgeting – like immediately increasing appetite when fasting. While levels drop quickly, eating can bring them back up, too. It has been shown to reduce lipids in muscle and other tissues which lead to insulin resistance (the first step towards type 2 diabetes). It even controls what foods we find appealing when we’re just looking at them. Basically, it seems like the perfect way to lose weight – just give people more leptin,  right?  Well, there is another factor at work.

Leptin Resistance

But when researchers gave people leptin in human clinical trials, people didn’t lose weight. The trouble is, your body constantly tries to adjust basal leptin levels. If there’s a lot of it all the time, like in obese and overweight people, the brain loses sensitivity. Mice can become leptin resistant after as few as 3 days of overfeeding – so it happens quickly in response to consistent high blood glucose levels.

When it does this, it takes more and more leptin before our bodies feel full. When we get fatter, our bodies produce more leptin, and we become resistant to it. So obese people actually have unusually high leptin levels, but are not responsive to it. Even when healthy people eat a much lower calorie diet for a little while,  levels decrease, and they feel hungrier and less energetic, even if they haven’t lost weight yet. To lose weight and keep it off, you have to give your body time to adjust to the new, lowered leptin level, so it sets that as “normal” and you feel full when you’re supposed to.

The bad news is that not just excess weight can lead to leptin resistance. A new study published in the American Journal of Physiology found that high fructose diets can induce leptin resistance. These sugars actually impair the leptin’s ability to cross the blood-brain barrier and reach the hypothalamus. So even when the leptin levels are high, not enough is reaching the brain to tell the body to stop eating.

How do you use this information to lose weight or keep healthy?

First things first: quit the crash diets. You aren’t going to do your body any favors by losing weight too quickly. If you are trying to lose weight, though, there’s one thing you can do to help your body out: cheat. Seriously.

When you cut calories dramatically, your body acts like its starving and your leptin levels plummet. You’ll be hungry and generally have lower energy levels and want to eat more. So, once a week or so, cheat. Really cheat. Have a nice, high-calorie meal.

Your body then senses the rush of fuel and boosts leptin levels, increasing your metablism and priming your body for fat loss. Cheating helps ease your body down to lower daily leptin levels without making it feel too starved. That way, as you lose the weight, your body adjusts and realizes that the reduced leptin levels are normal not starving. And you get to enjoy something delicious – come on, it’s a win-win!

Secondly, avoid too much sugar intake. High calorie loads aside, the sugars make your brain less sensitive to leptin, which causes you to eat more and pack on the pounds. Conversely, some foods have been shown to increase leptin activity and sensitivity. The biggest connection scientists have found is between Omega-3 Fatty Acids and leptin. That’s right – the ever remarkable fish just keep getting better and better.  Researchers found that a group of people who ate a high proportion of fish every day had lower leptin levels despite eating the same calorie loads and having the same body fat as their fish free cousins – suggesting that a fish-rich diet increased their bodies’ sensitivity to leptin.

There’s good news, too, for those that are already overweight and leptin resistant: it’s only temporary. Research has shown that reducing fat content in leptin-resistant, obese mice allowed them to regain leptin sensitivity. So even if you’re overweight and likely leptin resistant, you can improve on that state. Unlike type 2 diabetes and insulin resistance, which is very hard to reverse, leptin resistance is fairly correctable with a normal, healthy diet and exercise.

And lastly, there’s something really simple that everyone can do to keep their leptin levels high and keep cravings under control: sleep well. When you go to sleep, your leptin levels naturally rise – after all, you want to be sleeping, not snacking, so your body knows to cut down on your hunger while you’re resting. But if you cut your sleeping short, your body tries to adjust by making you hungry again. Research has found that shorter sleep periods (6 hours or less instead of  lower overall daily leptin levels, cause an increase in appetite, and even make people crave carbs and other fattening foods. So its important for your body to rest well to maintain its natural hormonal balance, allowing you to look and feel your best.

In summary:

• Stop crash diets
• Eat ONE large meal per week to spark leptin-based weight loss
• Avoid processed sugar
• Eat Omega-3 (in fish/flaxseed/walnuts)
• Sleep well

Like any other system in our bodies, the our hormonal appetite controls are sensitive to our daily habits and routines. The better a routine you have – sleeping well, eating right, and exercising, the more balanced your system will be and the better you will feel.

Stay tuned for more deep dives into the physiology of nutrition with the next installment of Understanding Our Bodies!

References:

1. Williams, K., Scott, M., & Elmquist, J. (2009). From observation to experimentation: leptin action in the mediobasal hypothalamus American Journal of Clinical Nutrition, 89 (3), 985-990 DOI: 10.3945/ajcn.2008.26788D
2. Havel, P. (2007). Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance Proceedings of the Nutrition Society, 59 (03) DOI: 10.1017/S0029665100000410
3. Huo, L., Gamber, K., Greeley, S., Silva, J., Huntoon, N., Leng, X., & Bjørbæk, C. (2009). Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons Cell Metabolism, 9 (6), 537-547 DOI: 10.1016/j.cmet.2009.05.003
4. Pratley RE, Nicolson M, Bogardus C, & Ravussin E (1997). Plasma leptin responses to fasting in Pima Indians. The American journal of physiology, 273 (3 Pt 1) PMID: 9316457
5. Chin-Chance C, Polonsky KS, & Schoeller DA (2000). Twenty-four-hour leptin levels respond to cumulative short-term energy imbalance and predict subsequent intake. The Journal of clinical endocrinology and metabolism, 85 (8), 2685-91 PMID: 10946866
6. Enriori, P., Evans, A., Sinnayah, P., Jobst, E., Tonelli-Lemos, L., Billes, S., Glavas, M., Grayson, B., Perello, M., & Nillni, E. (2007). Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons Cell Metabolism, 5 (3), 181-194 DOI: 10.1016/j.cmet.2007.02.004
7. Zelissen, P., Stenlof, K., Lean, M., Fogteloo, J., Keulen, E., Wilding, J., Finer, N., Rossner, S., Lawrence, E., Fletcher, C., McCamish, M., & , . (2005). Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial Diabetes, Obesity and Metabolism, 7 (6), 755-761 DOI: 10.1111/j.1463-1326.2005.00468.x
8. Wang, J., Obici, S., Morgan, K., Barzilai, N., Feng, Z., & Rossetti, L. (2001). Overfeeding Rapidly Induces Leptin and Insulin Resistance Diabetes, 50 (12), 2786-2791 DOI: 10.2337/diabetes.50.12.2786
9. Keim NL, Stern JS, & Havel PJ (1998). Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. The American journal of clinical nutrition, 68 (4), 794-801 PMID: 9771856
10. Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, & Scarpace PJ (2008). Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. American journal of physiology. Regulatory, integrative and comparative physiology, 295 (5) PMID: 18703413
11. Peyron-Caso E, Taverna M, Guerre-Millo M, Véronèse A, Pacher N, Slama G, & Rizkalla SW (2002). Dietary (n-3) polyunsaturated fatty acids up-regulate plasma leptin in insulin-resistant rats. The Journal of nutrition, 132 (8), 2235-40 PMID: 12163668
12. Winnicki M, Somers VK, Accurso V, Phillips BG, Puato M, Palatini P, & Pauletto P (2002). Fish-rich diet, leptin, and body mass. Circulation, 106 (3), 289-91 PMID: 12119240
13. Enriori, P., Evans, A., Sinnayah, P., Jobst, E., Tonelli-Lemos, L., Billes, S., Glavas, M., Grayson, B., Perello, M., & Nillni, E. (2007). Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons Cell Metabolism, 5 (3), 181-194 DOI: 10.1016/j.cmet.2007.02.004
14. Nedeltcheva AV, Kilkus JM, Imperial J, Kasza K, Schoeller DA, & Penev PD (2009). Sleep curtailment is accompanied by increased intake of calories from snacks. The American journal of clinical nutrition, 89 (1), 126-33 PMID: 19056602
15. Taheri, S., Lin, L., Austin, D., Young, T., & Mignot, E. (2004). Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index PLoS Medicine, 1 (3) DOI: 10.1371/journal.pmed.0010062