You May Be Leptin-Resistant. Here’s Why It’s Important.
In the diabetes world, leptin doesn’t get nearly the attention that other hormone, insulin, does. But leptin—called a master metabolic regulator—is pretty important, too. Leptin, which is inextricably linked to the insulin-resistance characteristic of Type 2 diabetes, is best known for moderating hunger. It also plays important roles in both blood glucose regulation and the body’s immune response. During the coronavirus pandemic, leptin may be more important than ever.
Leptin is a hormone excreted mostly by the body’s fat cells that has an important message for the brain: “You’re fat enough already. Stop eating so much.” When leptin levels are low, the brain should go into something like starvation mode, ramping up hunger and reducing energy expenditure to put on weight. When levels are high, hunger should abate and energy levels should increase, resulting in fat and weight loss.
The discovery of leptin in 1994 prompted hope that injections of exogenous leptin would be able to curb or even cure obesity. Rodent studies were initially promising—rats that had been bred to lack leptin grow to be massively obese, and return to normal body weight after they’re given leptin—but human trials have almost always been unsuccessful. The reason is that normal human obesity is at its heart a state of leptin resistance. Leptin isn’t functioning properly in people with obesity. They tend to have too much leptin, not too little.
Obese adults have essentially become inured to leptin’s signals, a problem that leptin injections actually only make worse. People with obesity can have such an overflow of leptin that the brain ignores the hormone’s message. What results is a classic vicious cycle: the brain, deaf to leptin’s call, believes that it needs to put on even more fat. Appetite rises, the poor sufferer puts on more fat, leptin resistance gets worse, and he or she only gets even hungrier.
In a sense, the failure of leptin therapy to treat obesity is reminiscent of the use of insulin as a therapy for Type 2 diabetes. While insulin will very effectively bring down high blood sugars, it also tends to exacerbate the underlying problem of insulin resistance, which has led some doctors to wonder if we should reconsider this treatment.
Leptin and Diabetes
Leptin resistance and insulin resistance are highly correlated, and are almost always found together in patients with Type 2 diabetes. Some have theorized that leptin resistance is directly caused by insulin resistance, although others have argued that it’s a case of the chicken and the egg.
Leptin is an important regulator of glucose metabolism, and when leptin signaling dysfunction leads to unpredictable blood sugars, the hyperglycemia characteristic of T2D just gets worse. At the same time, insulin resistance interferes with the brain’s ability to estimate leptin levels, leading to increase hunger and reduced energy. An excess of one hormone leads to an excess of the other, another vicious cycle.
And if you have Type 1 diabetes, it’s possible that you’ve already had at least one run-in with extreme leptin deficiency—a dramatic decrease in leptin secretion helps account for the voracious hunger that often accompanies undiagnosed or uncontrolled Type 1. When acute hyperglycemia is resolved with insulin treatment, leptin quickly skyrockets back up towards normal levels. Leptin deficiency is not generally considered to be a major problem in well-controlled Type 1 diabetes. (Unfortunately, given the rise of obesity and “double diabetes” among people with Type 1 diabetes in recent years, this view may soon have to change.)
Leptin, the Immune System, and COVID-19
Leptin also plays a vital role in the immune system, interacting with a dizzying number of immunological cells and processes, in both the innate and adaptive immune responses. While doctors have yet to identify all of leptin’s many immunological roles, there is enough evidence to propose that leptin is a critical connection linking the immune system with the metabolic system. High leptin concentration in the blood and leptin resistance lead to inflammation and immune system dysregulation; it’s no wonder that people with obesity get sicker from viral pathogens like the flu.
Uniquely bridging immunity and metabolism, leptin is now a subject of heightened interest due to the coronavirus pandemic. In a recent article in the International Journal of Obesity, researchers from Lousiana’s Pennington Biomedical Research Center suggest that the leptin dysfunction characteristic of obesity and diabetes—and the resultant impact on the immune system—may explains why metabolic disease is such a dangerous risk factor for those that have contracted COVID-19.
How do you reduce leptin concentrations and increase leptin sensitivity? Weight loss is paramount, as leptin is secreted in proportion to the amount of fat one has. Diets intended to reduce leptin resistance unsurprisingly tend to advise carbohydrate restriction. Researchers have blamed familiar foods as triggers for leptin resistance: sugar, fructose, refined grains and highly processed foods are all seen as the typical culprits.