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As we learn more about patients with COVID-19, and which conditions tend to cause either more severe symptoms or contribute to fatality, obesity continues to be one of the most direct contributors to both. I covered this in some detail in a previous blog, which provides a bit of foundation.

A new research paper submitted in the International Journal of Obesity, and led by the brilliant scientists at Pennington Biomedical Research Center (PBRC) references a link between leptin resistance, obesity, and the severity of COVID-19 response.

Incidence of Obesity

Obesity has become more than an epidemic, and during this COVID-19 pandemic, there has been multiple reports across the world of patients who are obese experiencing more severe symptoms and succumbing to the virus at a higher rate than those that are not obese.

The World Health Organization (WHO) estimates almost 2 billion (yes, ~30% of the world’s population) are either overweight or obese. Those considered overweight have a body mass index (BMI) of 25 – 29.9, and those who are obese have a BMI of 30+.

As the COVID-19 virus spread from China, it wreaked havoc around the world, with the elderly and those with chronic diseases being the hardest hit from a symptoms and fatality rate perspective. In the U.S., consider the following:

• The most commonly reported health conditions predisposing patients to require hospitalization are diabetes, cardiovascular disease (heart disease) and chronic lung disease.
• 89% of those who have diabetes are also overweight or obese
• Approximately 57% of the population has some type of cardiovascular disease
• Over 40% of the population is considered obese, and almost 70% is considered overweight or obese
• Obesity is a major contributor to chronic lung disease and even respiratory diseases like pneumonia
• In New York, which due to very poor decisions made by local leadership, age was the #1 driver of COVID-19 fatality. In younger patients, however, the primary driver of severe infection was obesity.

Hormones’ Role in Obesity

If you haven’t figured it out by now, the dated and disproven advice of “calories in = calories out” to manage weight and prevent obesity simply does not work. Since the 1960’s, Americans have been moving their diets toward lower fat & higher carbs, working out more and dieting more, and yet obesity rates have soared. Why?

Understanding the metabolism and the many factors that contribute to metabolic disease is complex and beyond the scope of this blog. However, there are four hormones that play a crucial role in obesity, at least two of which may offer clues as to why a pathogen like COVID-19 affects those who are obese worse than those who are not.

Ghrelin, Leptin, Insulin & Glucagon

The human body is built to seek homeostasis, which is a steady equilibrium of physiological interactions and processes. Consider how the four above-mentioned hormones work.

Hunger is triggered by a hormone called ghrelin found in the GI tract, that sends a signal to the brain indicating it is time to eat. In a state of hunger, the body has much more ghrelin than the balancing hormone, leptin. However, once food is consumed, and satiety is achieved, leptin is secreted to signal that the body is “full” and no additional food is necessary. These two hormones work opposite of one another to control satiety, seeking homeostasis.

Once food is consumed, the digestion process begins, and the body needs to pull the digested food (sugars, fats, proteins) from the blood and store it into cells & organs to enable to body to function. Enter insulin, which has the job of acting as a transporter with a key, moving nutrients from the blood and unlocking the cell so that those nutrients can enter, be stored and used to nourish the body. It’s important to note that when insulin is triggered, fat metabolism stops and fat storage is activated. Every time we eat, we spike insulin, and the biggest macronutrient insulin spiker? Carbohydrates, which account for 60% – 80% of our diet.

When we exercise or need energy, the body has to tap into those nutrient stores in the cells, unlock and convert nutrients to usable form, then transport that energy from the cells into the blood to fuel the body. This is the role of glucagon. Again, the body is operating in homeostasis as insulin and glucagon hormones control the storage and release of energy derived from food.

The quality, quantity/mix and frequency of our macronutrient consumption drives these hormones and the internal processes, and are major contributors to why our population has become so overweight and obese. High consumption of processed, sugary, high carbohydrate diets, combined with low quality fats like hydrogenated oils, and an endless snacking society have accelerated a downward spiral in health and wellness. This behavior also creates resistance, especially insulin resistance and leptin resistance. Think of this way:

• The more we eat poor quality foods and the more often we eat, the more we spike our insulin. The more often our insulin is spiked, the higher levels of insulin we have in our system, the less fat metabolism we experience while our bodies build up a resistance to insulin. The body becomes less sensitive to insulin, which means insulin is less effective at doing its job, so the body reacts by secreting more insulin to try and accomplish the job of nutrient storage.
• When insulin runs out of places to store nutrients because the cells are full, it converts the nutrients to fat to be stored in fatty tissue and in organs…especially the liver. The term “fatty liver” is not due to eating good quality fats; it’s a result of high amounts of carbohydrates and sugar that have been stored in the liver as fat due to excessive consumption.
• When the body becomes so insulin resistant (or desensitized) to insulin that it no longer can control blood sugar levels, that body has now entered into a Type II diabetic state.
• Of the three macronutrients (fats, protein & carbohydrates), carbohydrates spike insulin significantly more than the others, and contribute to both insulin resistance AND leptin resistance. This is because of the extreme blood sugar highs and lows that occur. With high carbohydrate consumption, blood sugars spike high, which means large amounts of insulin are released to move the sugar out of the blood. Once that occurs, blood sugar levels drop too low (ever notice how tired you get after a high carb meal?), which means the body then is concerned about life preservation (hypoglycemia, or low blood sugar, can be fatal), so ghrelin is secreted to signal the body to eat again to move blood sugar back into a safe range. Eating then spikes insulin, with the temporary satiation triggering leptin, and this cycle continues many times a day in our society, with our poor eating habits causing both insulin and leptin resistance. As a result, we gain weight (fat), develop chronic disease, become diabetic (type II), and experience significant physiological inflammation. And the cycle continues…

Leptin’s Possible Link to COVID-19

Leptin not only plays a role in the metabolic process, but connects metabolic process with immune response by aiding in the activation of immune system cells. As stated by PBRC:

The multifaceted nature of obesity including its effects on immunity can fundamentally alter the pathogenesis of acute respiratory distress syndrome and pneumonia, which are the major causes of death due to SARS-CoV-2 infection. Elevated circulating leptin concentrations are a hallmark of obesity, which is associated with a leptin-resistant state. Leptin is secreted by adipocytes in proportion to body fat and regulates appetite and metabolism through signaling in the hypothalamus. However, leptin also signals through the Jak/STAT and Akt pathways, among others, to modulate T cell number and function. Thus, leptin connects metabolism with the immune response.

An obese body suffers from insulin and leptin resistance as well as inflammation. Thus, the metabolic process is not in balance (homeostasis), and the resultant inflammatory conditions lead to heart disease, diabetes, chronic lung disease and other chronic conditions that place the body in a compromised immunogenic state. When a pathogen is then introduced, such as COVID-19, the already-compromised immune system is unable to fight off the virus, and then, in response to it, can over-react, causing a cytokine storm. Essentially, the body begins to attack itself, damaging cells and tissues instead of fighting off the virus. In a body that is already highly inflammatory, obese, and may be suffering from hypoventilation, this cytokine storm can prove fatal, as we have seen from COVID-19.

We continue to learn more about why COVID-19 has proven so destructive to the global population. But one thing is certain – our lifestyle is a major contributor to health and wellness, and if we have hope of creating a stronger, more resilient population to current and future pathogens, it starts with a seismic shift in our dietary behaviors. Our future is counting on it.