The hormone leptin has been found to be a major regulator of body weight and metabolism and dysfunctional leptin signaling results in one of many vicious cycles that prevent individuals from losing weight. With increased weight, leptin is secreted as a signal to the body to stop storing fat. Leptin stimulates metabolism, reduces appetite, and signals the body to burn fat. Studies are finding, however, that the ma­jority of overweight individuals that are having difficulty losing weight have varying degrees of leptin resistance. The leptin is un­able to produce its normal effects of weight loss, with the severity correlating with the degree of obesity and difficulty losing weight.

What is Leptin Resistance?

Leptin is a hormone that informs the body when it should be storing or burning fat. As the body acquires fat the amount of leptin circulating in the bloodstream increases. Unsurprisingly, many obese individuals suffer from increased leptin levels due to the excess fat that they carry. In a healthy system, an increase in leptin promotes sensations of fullness and informs the body that it should not store fat. However, when levels of leptin are maintained at a high level for an extended period the body can develop a resistance to leptin. This can result in weight-related dysfunction.

Reduced leptin receptivity makes the hypothalamus think that fat stores are depleted and should be restocked. This triggers the release of various hormones that inhibit fat utilization, encourage fat storage, and promote sensations of hunger. As fat continues to accumulate, leptin levels also rise which causes a subsequent worsening of leptin resistance and its associated weight-related issues. This cycle of decline can have a dramatic effect on bodily function and overall wellness.

The Thyroid Connection

The thyroid and metabolism are closely related and have a great deal of influence on weight regulation. Leptin resistance and increased leptin levels can disrupt thyroid function resulting in greater difficulty losing weight. As leptin resistance develops, signaling from the hypothalamus to the thyroid diminishes. This results in reduced secretion of TSH, slowed T4 to T3 conversion, and elevated levels of reverse T3. An imbalance of these hormones significantly disrupts metabolic function resulting in greater acquisition and retention of fat. It is common for those with leptin resistance to develop thyroid disorders such as hypothyroidism, which further impedes weight loss.

Signs and Symptoms

Symptoms of leptin resistance include:

  • Weight Gain
  • High leptin levels
  • Chronic inflammation
  • Inability to lose weight
  • Uncontrollable food cravings
  • Diet high in fat and high in sugar and processed foods

Potential Causes


Obesity is a leading cause of leptin resistance. Some studies suggest that the majority of overweight and obese individuals suffer from some degree of leptin resistance. Although excess fat is a primary contributor to leptin resistance there are other factors that contribute to its development as well.


Diet also plays a pivotal role in the development of leptin resistance. More specifically, leptin resistance is often caused by consuming a high volume of grains, processed foods, sugars, and other inflammatory foods metabolized by fat cells increases leptin release. If such a diet is sustained, leptin levels can remain elevated ultimately inducing leptin resistance. Additionally, yo-yo dieting that consists of periods of starvation followed by binge eating is known to lead to leptin resistance.


Stress is another major contributor to hormonal imbalances including leptin. Elevated stress levels also contribute to hunger, poor energy regulation, and often greater storage of fat. Similarly, lack of sleep can also disrupt hormone levels and activity. Make sleep a priority by scheduling a minimum of eight hours of sleep per night. This helps reduce both physical and mental stress while supporting hormonal balance.

Moreover, lifestyle factors such as excessive exercise, a lack of exercise, and excess exposure to toxins can also encourage leptin resistance.

Seeking Treatment

There is promising research that suggests leptin resistance can also be treated with medications. A study presented at the annual Obesity Society meeting demonstrated that new therapies treating leptin resistance are very effective for weight loss in overweight individuals with or without diabetes. In a randomized, double-blind placebo-controlled, cross-over trial, it was found that short-term use (less than 4 months) of the leptin sensitizing medication, resulted in significant weight loss in 65% of individuals. In the responders, 48% lost significant weight in two to four weeks with no change in diet. Individuals also experienced increased satiety vs. placebo. There were no reported side effects with treatment. Studies also show significant improvements in cardiovascular risk factors.

Leptin resistance is one of the most common contributors to obesity. In every case, leptin resistance must be assessed and optimized depending on individual patient factors. Employing general tips and hormone-supporting practices such as rebalancing diet, alleviating stress, improving sleep, and seeking appropriate medical assistance can be hugely beneficial in resolving leptin resistance thereby allowing healthy weight loss.

At Holtorf Medical Group, our physicians are trained to provide you with cutting-edge testing and innovative treatments to find the answers you deserve and a treatment plan that is personalized to your specific condition. If you’re experiencing weight retention and believe your hormones are to blame, give us a call at 877-508-1177 to see how we can help you!

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