All the food that we eat (e.g., proteins and carbohydrates) gives us energy and that energy can be stored in our bodies as reserves in the form of body fat. However, if energy is not being consumed and is instead constantly stockpiled then that can lead to fat accumulation. Anatomically speaking, obesity is the accumulation of triglycerides (the chemical term for fat) in adipose tissue (cells that store fat) when the previously stored fats are not being used up. But obesity is more complex than an imbalance of diet and exercise with direct and indirect causes ranging from biological to sociological. One relatively direct cause of obesity comes from not only the amount of food that we eat but also its quality.

With the advent of fast food and convenience stores, high-calorie foods and drinks with little nutritional value have become more available. These foods utilize artificial sweeteners, such as high fructose corn syrup and aspartame; which upon overconsumption can have a negative impact on our personal well-being. Living with obesity also increases the individual risk for other comorbidities (such as high blood pressure, diabetes, and arthritis) that can severely limit mobility and further maintain an obese state. Although artificial sweeteners can be utilized as sweeteners for a “diet option”, it has been shown that regularly drinking sugary beverages (which often contain artificial sweeteners) can at least double the risk of obesity.

That said, for a given individual, obesity can have a myriad of underlying factors. One factor is the body’s response to a hormone called leptin. Leptin is released by adipose tissue that the brain senses to assess energy levels and control food intake. Leptin interacts with proteins in the brain to trigger signals that decrease feelings of hunger and appetite. The amount of leptin in circulation is proportional to the amount of adipose tissue present in your body to produce it. Therefore, more adipose tissue leads to more leptin levels. This can have the consequence of leptin resistance because the brain becomes desensitized to constant high levels of the hormone. When leptin resistance occurs, the nervous system is unable to tell whether the appetite is satisfied causing it to signal an increase in hunger and promote overfeeding. This subsequently decreases metabolism at the same time leading to increased fat storage in adipose tissues.

Although leptin resistance can be congenital, it has been discovered that it can also be diet-induced with consequences for obesity and overall body metabolism. For example, laboratory mice fed a high salt diet (like fast food options) developed leptin resistance and obesity. The high salt diet also increases metabolic syndrome — conditions that increase the risk of heart disease and diabetes. In a separate study, nonhuman primates fed a fructose-rich diet developed fatty liver disease — a hallmark of obesity. Interestingly, one clinical study has shown that regular consumption of soft drinks (which contain high amounts of fructose) was the only observable marker for fatty liver disease when traditional risk factors were not present.

Obesity significantly increases the risk of developing a range of serious health conditions, including:

• Cardiovascular Disease and Strokes: Excess body weight contributes to elevated blood pressure and abnormal cholesterol levels, both of which are major risk factors for heart disease and strokes.
• Type 2 Diabetes: Obesity impairs the body’s ability to regulate blood sugar effectively, increasing the risk of insulin resistance and the development of type 2 diabetes.
• Increased Cancer Risk: Obesity has been linked to an increased risk of various cancers, including those of the uterus, cervix, endometrium, ovary, breast, colon, rectum, esophagus, liver, gallbladder, pancreas, kidney, and prostate.
• Gastrointestinal Issues: Carrying excess weight increases the likelihood of conditions such as gastroesophageal reflux disease (GERD), gallbladder disease, and fatty liver disease.
• Sleep Apnea: Individuals with obesity have a higher risk of sleep apnea, a condition where breathing repeatedly stops and starts during sleep, leading to poor sleep quality and other complications.
• Osteoarthritis: The additional strain on weight-bearing joints, combined with systemic inflammation associated with obesity, significantly increases the risk of developing osteoarthritis, which manifests as joint pain, stiffness, and swelling.
• Non-Alcoholic Fatty Liver Disease (NAFLD): Obesity can lead to the accumulation of fat in the liver, increasing the risk of non-alcoholic fatty liver disease (NAFLD). If left untreated, NAFLD can progress to liver cirrhosis or failure.
• Chronic Inflammation and Immune Dysfunction: Obesity is associated with chronic low-grade inflammation, which can impair immune function. This makes individuals more susceptible to infections and may hinder wound healing.
• Kidney Disease: Obesity increases the risk of developing chronic kidney disease (CKD) due to its effects on blood pressure, blood sugar control, and the development of glomerulopathy, a kidney condition caused by excess weight.
• Polycystic Ovary Syndrome (PCOS): Women with obesity are at a higher risk of developing PCOS, a hormonal disorder that can lead to irregular menstrual cycles, infertility, and metabolic disturbances.
• Infertility and Reproductive Issues: Obesity can impact reproductive health in both men and women by disrupting hormonal balance. In men, it may lead to reduced testosterone levels and impaired sperm quality.
• Mental Health Disorders: Obesity has been linked to an increased risk of depression, anxiety, and low self-esteem. Research suggests that the stigma and social discrimination associated with obesity contribute to psychological distress.
• Venous Thromboembolism (VTE): Individuals with obesity are at a higher risk of developing blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (PE), due to reduced mobility and increased inflammation.
• Gout: Obesity can increase uric acid levels in the blood, increasing the risk of gout, a form of inflammatory arthritis characterized by severe joint pain and swelling.
• Cognitive Decline and Dementia: Emerging research suggests that obesity, particularly in midlife, is linked to an increased risk of cognitive decline, Alzheimer’s disease, and other forms of dementia, possibly due to inflammation and vascular damage.
• Asthma and Respiratory Disorders: Obesity can exacerbate asthma and other respiratory conditions due to increased airway resistance, reduced lung volume, and systemic inflammation.
• Peripheral Artery Disease (PAD): Obesity contributes to the development of atherosclerosis, which can narrow arteries and lead to PAD, a condition that reduces blood flow to the limbs and increases the risk of amputation.
• Gallstones: Excess weight increases the risk of gallstones due to changes in bile composition and reduced gallbladder motility.

Hormonal regulation is not the only factor that can influence a tendency toward obesity. The gut microbiome provides a bacterial component to obesity through its role in nutrient and energy uptake during digestion (also called fermentation). Microbiome samples from both lean or obese human and mice samples highlighted a dynamic between two groups of bacteria — the Bacteroidetes and Firmicutes — as partly responsible for changes in metabolism. A high Firmicutes population coupled with a low Bacteroidetes population increased the efficiency of energy uptake for the host. Although that sounds favorable, it has a negative consequence. The greater the rate of fermentation, the more the bacteria want energy as well — further driving the need to consume more energy (i.e., eat more). The influence of gut bacteria affecting host energy uptake was further demonstrated in a comparison between the effects of the gut microbiome in mice fed a high-sugar/high-fat diet versus sterile mice (i.e., no gut microbiome) fed the same diet. Mice fed with the high-sugar/high-fat diet had decreased levels of two protein regulators: fasting-induced adipose factor (a regulator of metabolism) and phosphorylated AMPK (a regulator for fatty acid breakdown — the building blocks of triglycerides). In contrast, mice lacking the gut microbiome had higher amounts of fasting-induced adipose factor and phosphorylated AMPK; and did not become obese despite being fed the same high-sugar/high-fat diet. Taken all together, it is becoming understood that energy levels and hunger come from as much the needs of the gut microbiome as one’s own needs.

Harmful gut bacteria can significantly influence weight gain by disrupting the integrity of the gut lining. When this barrier weakens, harmful substances like lipopolysaccharides (endotoxins) enter the bloodstream, causing inflammation. This inflammation alters metabolism and gut microbiota, promoting obesity. Studies reveal that individuals with obesity often have elevated endotoxin levels, underscoring the critical link between gut microbiome and obesity.

Improving gut health through diet and lifestyle changes is key to managing weight gain. Incorporating more fiber, prebiotics, and probiotics into your diet promotes the growth of beneficial bacteria. Regular exercise also supports a balanced gut microbiome. Emerging treatments like fecal microbiota transplantation (FMT) are being explored to restore gut balance in individuals with gut dysbiosis. Combining these strategies with other lifestyle interventions provides a holistic approach to addressing obesity.

Obesity is clearly more than meets the eye. Even social factors such as environment (e.g., availability of supermarkets versus convenience stores) and affluence (e.g., being able to afford/prepare high-quality food versus eating what is cheap/readily available) are considerations when tying down causes of obesity. However, at an individual level, we can still meaningfully monitor our own weight-related tendencies by being aware of what we eat and who lives in our gut.