Four Ways to Prevent Leptin Resistance

If you’re a member of “The Clean Plate Club,” learning to put down your fork while you’ve still got some food left on it might be the most important skill you need to achieve your goal weight. Portion control, after all, is critical to maintaining a healthy body weight. But what if no matter how much you eat, you’re still starving? Resistance to leptin, the hormone that tells our brain that we’re no longer hungry, might be the culprit. In healthy people, leptin hormone acts as an appetite suppressant.

The easiest way to prevent cellular leptin resistance is to avoid becoming overweight in the first place—but that’s easier said than done. Unfortunately, obesity is at an all-time high in the United States, where it affects approximately four out of ten people, and obese people actually produce more leptin hormone because of their resistance to it.^{1, 2}

Does that mean your leptin resistance ship has sailed, and you’ll be destined to feeling unsatisfied after meals…forever? Good news: Not only can leptin resistance be prevented, but it potentially can be reversed.

How Our Hormones Tell Our Brains to Stop Eating

Whether you go for seconds or push away your plate isn’t just about willpower—that’s where leptin signaling plays a critical role. Secreted by our fat cells (called adipocytes), leptin has two major jobs. The first job is to let the brain know when we’re no longer hungry, so we’ll stop eating. The other is to power our bodies with energy from food intake, by breaking down the triglycerides in our fat cells. When these jobs are done in harmony, the body properly regulates its balance of energy.

It’s when we lose sensitivity to the effects of leptin that we start tuning out that voice that says it’s time to stop eating. Cellular leptin resistance has been compared to insulin resistance that occurs during weight gain, when cells’ sensitivity to insulin becomes impaired, resulting in less utilization of insulin by the cells and higher levels in the blood. Similarly, resistance to the effects of leptin increase with the amount of body fat an individual accumulates.

How Do You Know if You Have Leptin Resistance?

People who are resistant to the effects of leptin signaling experience nearly constant hunger, which can lead to increased food intake and further weight gain. It’s a self-perpetuating cycle, because weight gain increases leptin resistance. Perhaps this sounds like it fits you to a “T”—you’re always hungry—so how do you know for sure? A leptin blood test can indicate the leptin concentration circulating in your body, proportionate to your level of body fat. High leptin level will indicate that indeed, you are resistant to the hunger suppressant powers of this hormone.

What Causes Leptin Resistance?

If you’re not passing along enough leptin to the brain, you won’t benefit from the hunger suppressing effects of this hormone—and this appears to happen when there’s an interruption or impairment of the mechanism that conduct leptin transport.² One proposed culprit is the binding of C-reactive protein (CRP, a biomarker of inflammation) to leptin, which would hamper it from traveling to the brain.³ Since fat cells release CRP and obese subjects have more fat cells than average-weight people, the result would be less leptin entering the brain, culminating instead in higher blood levels.

Another possible cause of leptin resistance might be changes to the actual structure of the leptin molecule, causing leptin receptor function—including signaling to the brain—to deteriorate.⁴

Four Ways to Decrease Leptin Resistance

If learning about leptin is making you wish yours functioned normally, there are multiple strategies to help you reverse low leptin responsiveness.

1. Lose weight to regain normal leptin levels

Reducing body fat can increase your sensitivity to leptin, and the best way to do this is by losing weight. But this can be a catch-22, since dieting can be challenging when leptin resistance makes it harder for you to feel satisfied after each meal. You’ll want to eat strategically, choosing foods that contain a significant amount of fiber, such as vegetables, fruit and legumes, to help you feel fuller after a meal. Fiber supplements, such as ground psyllium seeds or flax seeds, consumed with a glass of water before a meal, might help.

Still hungry? Consider supplementing with the extract of white kidney bean, which may help suppress your appetite. According to research, this nutrient may help modulate the activity of hormones cholecystokinin (CK) and glucagon-like peptides (GLP).⁵ A small, randomized trial that compared the effects of white kidney bean extract to a placebo resulted in lower glucose and insulin levels during the three hours following a meal among those who received the extract. Satiety after three hours was significantly less in the placebo group than those who received white kidney bean extract, who experienced a decreased desire to eat.⁶

White kidney bean extract also helps reduce absorption of carbohydrates, decreasing their breakdown during digestion, by inhibiting the enzyme alpha-amylase. This can contribute to better weight management.⁵

Another popular weight management aid is Irvingia gabonensis, or African mango. In a randomized trial lasting 10 weeks, 102 overweight or obese subjects were either given African mango capsules or a placebo. The non-placebo group demonstrated significant reductions in body weight, body fat, waist circumference and other factors—including leptin.⁷

2. Lower your triglycerides to reduce overall leptin level

In addition to losing weight, you’ll want to reduce your triglycerides. This is because your body fat is stored as triglycerides within your fat cells; when you have a large amount of triglycerides, the fat cells expand, and your leptin resistance will increase.⁸ The triglyceride-lowering drug, gemfibrozil, improved leptin transport in studies. Ask your doctor about medication.

What you eat may impact your triglycerides. According to preclinical research, foods that contain triglycerides, such as milk, may make it harder for leptin to move across the blood-brain barrier, a phenomenon that occurs during leptin resistance.⁸ Both obesity and starvation were associated with elevated triglycerides and decreased the transport of leptin into the brain, experimental research has determined.

3. Exercise to fight leptin resistance

If you’re trying to lose weight, exercise is a great way to burn calories and increase energy expenditure. It also may help combat leptin resistance, according to research. A trial reported in the American Journal of Clinical Nutrition found significant reductions in once elevated leptin among 186 men who improved their diets and exercised, alone or in combination for one year, in comparison with a control group who participated in neither intervention.⁹

The authors of the report noted that physical activity and energy expenditure may decrease leptin messenger RNA expression and lower the abdominal tissue leptin production rate, based on the findings of other studies. “Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass,” the researchers concluded.⁹ This isn’t the research suggesting that working out can reduce leptin resistance; a study involving obese rats found that exercise improved sensitivity in peripheral leptin tissue.¹⁰

4. Supplement with ginseng

The herb ginseng contains the compound ginsenoside Rb1, which may increase leptin sensitivity—so you’ll feel full when you’ve eaten adequately. A study in mice that were made obese by consuming a high fat diet found that ginsenoside Rb1 improved leptin sensitivity and signaling, in addition to improving leptin-induced regulation of brain-derived neurotrophic factor, which stimulates the growth of connections between neurons in the brain.¹¹ Consider adding this herb to your supplement regimen in addition to these other fat-fighting tactics.

End the leptin resistance cycle—once and for all

The easiest way to prevent leptin resistance is to avoiding gaining excess body fat. This doesn’t always mean a low body weight—after all, athletes who have more lean tissue mass may weigh more than what is considered “normal” for their height and have a high body mass index and a low amount of body fat. But having normal body fat levels are key to normal leptin levels. Once you’re sensitive to this hormone, you’ll find it easier to push away the plate and say, “No thanks!” when you’re offered seconds.

References

1. “Overweight & Obesity.” Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, last reviewed 29 Jun 2020, https://www.cdc.gov/obesity/data/adult.html
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