Weight balance is a matter of chemicals and not choices we make. It is complicated. Of course, poor choices can only make things worse. Believe it or not, weight loss isn’t just about eating fewer calories or having more willpower, and it’s a far more complex interchange of biology, genetics, food choices, and the environment.

From an evolutionary perspective, our bodies were designed to store fat for times of famine. This may have been helping thousands of years ago when we had to hunt and gather our food. Still, today, when there’s often more than enough food to go around, the body’s drive to squirrel away fat for lean times is working against us. So it's not surprising that our bodies have such a complex system to control food intake, driven by hormones as well as neurochemicals. In this pursuit for survival, the body is assisted by stubborn hormones such as leptin and ghrelin, which ensure that you won’t starve to death but can also undermine willpower. Hormone levels change when weight changes. For people trying to lose weight and or maintain it, increased hunger after weight loss is a major challenge. Hormones from the body signal to the brain, affecting food intake. The body's system for regulating food intake is coordinated by the hypothalamus, which is located under the midline of the brain, behind the eyes.

How does the brain regulate appetite and weight?

The brain is the master regulator of food intake. Let’s take a simplistic look at neuroanatomy and neurochemistry which help maintain energy balance, hence weight. This will help understand the complexity of the weight balance system. The hypothalamus is a command center for several vital functions. Within the hypothalamus are nerve cells that, when activated, produce the sensation of hunger. They make two proteins that cause hunger: neuropeptide Y (NPY) and agouti-related peptide (AGRP). Quite close to these nerve cells is another set of nerves that powerfully inhibit hunger by producing two different proteins: cocaine and amphetamine-regulated transcript (CART) and melanocyte-stimulating hormone (αMSH). These two sets of nerve cells initiate and send signals to other areas of the hypothalamus. So, whether you feel inclined to eat or not depends on the balance of the activity between these two sets of neurons.

But what determines which set of neurons dominates at any given time?

The activity is controlled by hormones circulating in the blood, produced by various parts of the body that regulate energy (food) intake and storage. These include the gut (receives and digests the food), the fat (stores the energy), and the pancreas (makes hormones that are involved in energy storage, such as insulin). Let's take a closer look at how each of these hormones works.

Ghrelin is made in the stomach. It stimulates hunger by acting in the hypothalamus to increase the hunger-causing nerve cells' activity and reduce the activity of hunger-inhibiting cells. When you haven’t eaten for a few hours, ghrelin levels rise to let your brain know that it’s time to eat again. Ghrelin levels also increase when you lose weight, prompting you to eat more and simultaneously slowing your metabolism—the rate at which your body uses calories. As the stomach empties, the release of ghrelin rises, and as soon as the stomach is filled, it decreases.

Insulin-like peptide 5 (ILP-5) is mainly produced in the colon and stimulates hunger.

Cholecystokinin (CCK) is produced in the upper small bowel in response to food and gives a feeling of fullness.

Peptide YY, glucagon-like peptide 1 (GLP-1), oxyntomodulin, and uroguanylin are released from the last part of the small bowel in response to food in the gut. They make us feel full.

Leptin is the most potent appetite-suppressing hormone and is made in fat cells. The more fat cells we have, the more leptin the body produces. Like a gas gauge in a car, it tells your brain when you have enough fuel onboard. When you lose weight, a low leptin level signals your brain that you are going on empty and need to fill up.

Amylin, insulin, and pancreatic polypeptide are made in the pancreas. These hormones promote satiety.

The hypothalamus also receives signals from pleasure pathways that use dopamine, endocannabinoids, and serotonin as messengers, influencing eating behavior.

Once full, the stomach reduces the desire to eat by lowering ghrelin production and sending a message to the hypothalamus. Ghrelin levels reach a low around 30 to 60 minutes after eating.

Levels of hormones that make us feel full – CCK, PYY, GLP-1, amylin, and insulin – increase after a meal to reach a peak about 30 to 60 minutes later. 

All the hormones then gradually return to their fasting levels three to four hours after a meal.

How weight loss affects our hormones

From a big-picture perspective, we humans are hard-wired to survive and propagate the species. So it makes sense that a decrease in food intake (calorie deficit) would signal our brain to conserve energy and increase the drive to eat to stop us from wasting away to death. Even though you may desperately want to shed excess fat, your brain has other plans—hanging on to as much fat as it thinks you require for survival. To this end, it works like a thermostat, constantly monitoring hormones such as leptin that provide feedback on body fat levels. When you eat less and lose weight, your brain jumps in, working to restore equilibrium by sending out hunger signals and—to make matters worse—slowing your metabolism. Following weight loss, leptin levels decrease profoundly. Other hormonal changes include increases in circulating ghrelin, GIP, and pancreatic polypeptide and reductions in PYY and CCK. Almost all of these changes favor regaining lost weight by increasing hunger, reducing satiety, and improving the capacity to store fat. These hormonal changes seem to be present for at least one year after weight loss, leading to a persistent increase in hunger.

The brain’s reward system only adds to the challenge by encouraging you to seek out high-fat, high-calorie food. This strategy was used to aid survival when food was scarce but works to our detriment today. While our biology hasn’t changed much, our food supply has, especially over the past 50 or so years—a very rapid change in the context of the nearly 200,000 years of human evolution.

What about your genes?

We are not destined to be sick. Genes load the gun, but the environment is a trigger. Our bodies are programmed to store fat and to maintain those fat supplies for times of scarcity. Yet some people seem to put on weight faster than others. The reason could be genetic. To date, scientists have uncovered 445 different genes that have been linked to some aspects of obesity. For example, certain people are born with a genetic mutation that results in congenital leptin deficiency, which causes severe obesity as early as infancy. People with this condition are average weight at birth, but because they don’t produce sufficient leptin, they are always hungry and quickly add weight. Other genes appear to contribute to excess weight by promoting one of the following:

slow metabolism and low calorie-burning rate

a propensity to be physically inactive

a reduced ability to burn calories from fat

a tendency to develop excess fat cells and store high levels of body fat.

The power of genetic influences on weight varies substantially from person to person and could account for anywhere from 16% to 40% of the variation in body mass index, according to studies of twins. In general, if both of your parents or other close blood relatives are significantly overweight, you’re much more likely to develop obesity than a person without a family history of being overweight. If you have a strong family history of obesity, especially severe obesity, genes are likely involved.

However, biology is not destiny. Even people with the so-called fat mass and obesity-associated (FTO) gene—the first gene discovered that contributes to common types of obesity—are much less likely to be overweight if they engage in a high level of physical activity. Dietary changes can also benefit people with a number of other obesity-related genes. And in some cases, improvements in gut bacteria may even help.

Bottom line: you cannot change your genes, but you can control your environment—and it is the environment we live in that has driven the dramatic increase in obesity since the 1970s.

Should you be counting calories?

Most people have been taught that losing weight is a matter of simple math. Cut calories — specifically 3,500 calories, and you'll lose a pound. But as it turns out, experts are learning that this decades-old strategy is actually pretty misguided. This idea of a calorie in and a calorie out when it comes to weight loss is not only antiquated, it's just wrong. The truth is that even careful calorie calculations don't always yield uniform results. Now, experts realize strict calorie counting isn’t the best strategy. Over the long term, your weight is controlled more by biology than willpower. You can temporarily cut calories and lose weight, but your body pushes back with rising hunger and slowing metabolism.

How your body burns calories depends on a number of factors, including the type of food you eat, your body's metabolism, and even the type of organisms living in your gut. You can eat the exact same number of calories as someone else, yet have very different outcomes when it comes to your weight.

When you rely solely on counting calories, you never learn to listen to your body’s inner hunger and satiety signals, which can be powerful tools in helping to keep unwanted pounds off for good. Drop the calories notion. That’s not to say calories don’t matter at all, but you don’t need to obsess about them. It's time to take a different approach, putting the emphasis on improving diet quality and making sustainable lifestyle improvements to achieve a healthy weight. It can be more helpful to have a general idea of how many calories you should limit yourself to in a day—and which foods are more likely to help you stay within that range. Think of it as calorie awareness, as opposed to calorie counting.

Not all calories are created equal

Experts are also now learning that not all calories are created equal when it comes to weight loss. Some foods can keep you far more satisfied than others, helping you eat less overall. Three main factors affect how your body processes calories:

Gut microbiome

Your gut is home to more than 100 trillion microbial cells. That’s ten times the number of human cells in your body. These microbes are incredibly diverse, with 1,150 different species that can potentially live in your gut. They have all sorts of essential jobs, such as regulating immune and digestive health and even influencing your mood. Now, research is finding links between the types of bacteria you harbor and your body weight. Different microbes have different effects on weight. Some may help you stay slim by stimulating the production of hormones that keep you feeling full, such as leptin. Others may promote weight gain by increasing the fermentation of carbohydrates, encouraging the body to absorb more of its calories. Still, other microbes may prompt the body to store more significant amounts of fat. In general, the greater the diversity of microbes, the better, since the “good” ones can help counteract the “bad.” People who are naturally thin have different types of organisms living inside them than those who are overweight. Taking the gut microbiota out of people who are lean and placing it in people who have overweight or obesity can result in weight shifts. This may occur because some types of organisms in the gut are able to break down and use more calories from certain foods than other types of organisms.

The foods you eat and your environment determine your unique gut bacterial profile. A diet containing many fiber-filled plant foods appears to protect against obesity-causing bacteria. In contrast, the typical Western diet—rife with sugar, fat, and animal products—has been linked to microbes that promote weight gain. Amazingly, it doesn’t take long to alter the composition of your gut bacteria. In one Harvard study, researchers found that changes in diet could affect a person’s gut microbes in as little as one day.

Set point

Each body has a "set point" that governs weight. The "set point" theory supports the notion that the brain acts to keep your weight within a specific range. A good comparison is to think of a thermostat - despite efforts or opening windows, the room will return to its designated temperature. This set point reflects several factors, including your genes, your environment, and your behaviors. Your hypothalamus, which also regulates things like your body temperature, stands guard to keep your body weight from dipping below that set point—which is not really an advantage if you're trying to lose weight. This is why you might find your weight plateauing even if you are diligently dieting and exercising, and also why many people who lose a large amount of weight regain it.

Researchers studying the show The Biggest Loser, which helps contestants lose large amounts of weight through a stringent plan of diet and exercise, found that after weight loss, contestants' bodies would fight back in an attempt to regain weight. The resting metabolic rate for contestants, which measures the number of calories the body uses just running its everyday functions, plummeted after their dramatic weight loss. This means it became very challenging to avoid regaining some weight because of metabolic adaptation.

Food

Your food choices influence your calorie intake, and not just because of their specific calorie content. One 2019 study published in Cell Metabolism found that eating processed foods seems to spur people to eat more calories compared with eating unprocessed foods. In the study, 20 people (10 men and 10 women) were split into two groups. They all were offered meals with the same number of calories, as well as similar amounts of sugar, sodium, fat, fiber, and micronutrients. But there was one key difference: one group was given unprocessed foods, and the other got ultra-processed options. After two weeks, the groups switched and ate the other type of diet for the following two weeks. People who ate ultra-processed food gained weight. Each group was given meals with the same number of calories and instructed to eat as much as they wanted, but when participants ate the processed foods, they ate 500 calories more each day on average. The same people's calorie intake decreased when they ate unprocessed foods.

Processed food

Processed food is any food that has been altered from its natural form. While not all processed foods are unhealthy, ultra-processed foods have been changed the most from their natural form & are the least healthy. Added fats, added sugar, salt and refined grains injure brain cells to raise the setpoint. It overstimulates rewards from calorie-dense foods with low nutritional value.

Few minimally processed food are:

Canned beans

Bagged salads

Roasted nuts

Frozen vegetables

Few ultra-processed foods are:

Deserts and chips

Frozen entrees

Sugar-sweetened beverages

Fast food

Deli meats

Whole Food

Whole foods are foods closest to their natural form: fruits, vegetables, beans, nuts, & seeds. They contain high amounts of complex carbohydrates and are high in fiber. They contain mostly monounsaturated and polyunsaturated fats. They have low-calorie density, high in nutritional values, and don’t change the set point.

So, not all food is created equal. The brain likes foods that are healthy, that are in their natural form.

What should you do?

Focus on diet quality

When planning your meals, focus on choosing unprocessed foods, including lean meats, whole grains, and lots of fruits and vegetables in their natural form. Identify your comfort foods, and keep them out of your house. Processed food can drive your body to consume more.

Exercise regularly

Power your metabolism with exercise. Physical activity is a wellness tool. Aim to get at least 150 minutes of moderate-intensity exercise each week. Moderate exercise is done at a level where you can talk, but not sing. Moderate exercise is not a casual walk, but it's more like walking up a large hill.

While any movement is better than nothing, work toward achieving a more vigorous level of exercise when you can. The type of physical activity (eg aerobic vs resistance; high intensity vs low intensity) does not seem to affect overall weight loss, but as more intensive activity produces similar weight loss with a reduced time commitment, they might be preferable to some.

Splitting a continuous bout of exercise into shorter bouts of equivalent total duration spread over the course of a day does not alter its potential to provide health benefits. For people engaged in sedentary work, we recommend getting up and walking for 10 minutes every hour on the hour. This will help them walk at least 2 hours by end of the day, which offers a great health benefit.

Although both food quality and exercise are important in weight management, food is more important in the process of losing weight while exercise is more important in the process of maintaining weight.

Sleep well

Poor sleep quality can lead to weight gain, as can a sleep schedule that is out of sync with the body's natural daily pattern, known as circadian rhythm. Your body wants to sleep at night and be awake during the day. "The Nurses' Health Study, which followed nurses for 20 years, found that those who worked the night shift gained more weight over time. The body gets perturbed when you disrupt its natural rhythm. The same is true if you are getting poor-quality sleep or not enough. A lack of sleep affects your weight in much the same way as hormonal shifts, making you want to eat more. So, addressing sleep problems should be a priority.

Manage stress

Stress is part of our lives. Stress, like poor sleep, can lead to weight gain. Controlling stress can help you keep excess pounds at bay. Stress drives us to eat comfort food to soothe negative feelings & chemically dial down our stress response. Stress hormones lead to an accumulation of belly fat - which releases chemicals that cause inflammation & insulin resistance, leading to further weight. Stress triggers can be external (related to a job, relationships, or major life changes) or internal (challenges to health or mental wellbeing). We can't always change the situation that causes stress. By recognizing triggers, we can become better at responding to stress. Managing stress is an integral part of living a healthy life. Stress management techniques that build resilience to stress can lower our level of stress hormones & improve how we regulate our appetite & weight. A few techniques for handling stress are:

Cultivating gratitude

Building Optimism

Investing in relationships

Finding meaning and purpose

Seeing the Cup Half Full

A healthy meal is self-nurturing, which tends to body signals and needs. It’s clear, that having an unhealthy weight isn’t a matter of personal failing. Our goal is to help simplify the complex process of weight balance and give you self-help tools to attain and maintain health and wellbeing.

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About Us

Dr. Amar Singh, MD, and Dr. Poonam Singh, MD, are board-certified by the American Board of Internal Medicine and the American Board of Obesity Medicine. They specialize in preventing, treating, and reversing chronic diseases using an evidence-based holistic approach. They are specifically interested in weight management, hormone re-balancing, and longevity. The American College of Physicians has recognized them as Fellows, FACP, for their excellence and contributions to medicine and the broader community. They enjoy teaching, volunteering, and advocating for their patients. Their mission is to share simple, effective, and proven strategies that lead to meaningful, sustainable, and long-lasting well-being.