Hormonal Factors in Obesity: Exploring the Roles of Leptin, Insulin, Sex Hormones, and Growth Hormone

Obesity is a major public health concern, affecting billions of adults worldwide. With prevalence rates on the rise, experts are attempting to understand the underlying pathophysiology of weight gain and contributing factors to obesity. While we all know that diet and affect weight, many may not understand how the endocrine system and hormones contribute to obesity. This article will explore how certain hormones, including leptin, insulin, growth hormone, and sex hormones, affect weight gain, fat distribution, and one’s risk of obesity.

What is obesity?

Obesity is a global public health issue, as 1.9 billion adults are defined as overweight and more than 650 million adults are defined as obese. The prevalence of obesity is rising at an alarming rate, as the number of obese individuals has almost tripled between the years of 1975 and 2016. Amongst all adults, 39 percent of men and 40 percent of women are considered overweight (1).

There are many causes of obesity, but what underlies excess weight is disproportionate consumption of calories consumed versus calories burned. The uptake in foods high in sugar and fat, coupled with a sedentary lifestyle, contribute to this imbalance (1). However, there are several underlying pathological processes that may influence one’s ability to gain excess weight, including hormones.

How does the endocrine system influence weight?

The endocrine system is a network of glands and organs, which include the hypothalamus, pituitary gland, thymus, pineal gland, thyroid gland, adrenal glands, parathyroid glands, and pancreas. These structures work by producing and releasing hormones into the bloodstream. From the bloodstream, hormones are transported throughout the body to different tissues and organs, executing a multitude of functions and processes (2). Hormones are chemical messengers that signal your body to act and function in certain ways – communicating what to do, how to do it, and when to do it.

The endocrine system’s hormones play key roles in things such as reproduction, metabolism, growth, and development (2). With regards to metabolism, the hormones leptin, sex hormone, insulin, and growth hormone can all influence weight. These messengers regulate things like appetite, distribution of body fat, and the storage of extra food as fats. Obesity causes abnormal levels of these hormones, contributing to excess body fat and dysregulated fat metabolism (3).

Leptin and obesity

Leptin is an important hormone as it helps regulate your body weight long-term. In the body, adipose tissue, which is body fat, produces leptin. Leptin works on the brainstem and hypothalamus, although there are also leptin receptors outside of these areas in other parts of the body as well.

Leptin hormone controls feelings of satiety, or fullness, thus maintaining your hunger levels. It does so by telling your body it is not hungry, preventing you from consuming excess calories. However, leptin does not work on a meal-by-meal basis. Instead, it regulates food intake and energy balance over an extended period to maintain your weight.

Though leptin levels are not a routine lab that healthcare providers order, normal leptin levels in females are between 0.5 to 15.2 nanograms per millileter (ng/mL) and 0.5 to 12.5 for males. The amount of leptin you have correlates to how much body fat you have. If you have little body fat, you will have less leptin. If you have more body fat, you will have more leptin. Thus, obesity causes high leptin levels. High levels of leptin can result in leptin resistance.

Leptin resistance occurs when your body is continuously exposed to leptin, and thus it does not mount an adequate response to leptin. Because leptin does not produce as profound effects, you do not feel full or satisfied after eating. Likewise, you are likely to continue eating more food despite having already eaten enough. This causes weight gain due to hunger and lowered metabolism.

Leptin resistance prevents leptin from stopping your appetite. Thus, a symptom of leptin resistance is a state of constant hunger and eating despite having enough body fat.  High levels of leptin can also cause other conditions outside of obesity. These include things like depression, nonalcoholic fatty liver disease, depression, and neurodegenerative conditions (4).

Insulin and obesity

When people think of insulin, they may just think of diabetes. However, insulin is a key hormone that is implicated in the regulation of everyone’s blood sugar. It controls blood sugar by telling the body how to store fat and glucose. To do so, it communicates to several entities, such as the muscles, liver, and fat cells, to intake glucose from the blood for fuel. With diabetes, individuals either do not make insulin or do not respond sufficiently to it.

Insulin resistance is an important phenomenon to consider both with regards to diabetes and obesity. Insulin resistance occurs when the body becomes resistant to insulin. When this happens, the body requires higher amounts of insulin to induce the same effect.

Insulin resistance is the result of both your lifestyle and genetic factors, including excess food. With excess food intake, the body attempts to sustain a normal blood sugar level. To do so, the pancreas’ beta cells release more insulin, but in turn the cells become less sensitive to insulin. In lab work, this manifests as increases in blood sugar levels, HgbA1c, and triglycerides.

Risk factors for insulin resistance include things such as weight gain in the abdomen, increased waist circumference, increased triglycerides, and increased LDL-C (bad cholesterol). Likewise, obesity is intimately linked to the development of insulin resistance.

Thankfully, losing weight can help with insulin resistance. Because insulin production is increased, free fatty acid levels also increase, resulting in inflammatory signaling that dysregulates insulin function. Losing weight can help to minimize this inflammation and the amount of free fatty acids, improving insulin resistance. Additionally, physical activity may help to treat insulin resistance in addition to weight loss. Certain dietary changes can help as well, such as choosing foods that have a low impact on insulin stimulation, like those high in fiber and healthy fats. Additionally, avoidance of processed and sugary foods can help (5).

Growth hormone and obesity

Human growth hormone (HGH) is a natural hormone produced by the pituitary gland. It works during childhood to promote growth and development. In adulthood, growth hormone is still critical to maintaining your body’s physical structure. Additionally, it is implicated in your metabolism, and plays a key role in regulating blood sugar levels.

Growth hormone affects metabolism by increasing the amount of insulin-like growth factor-1 (IGF-1) in the body. IGF-1 works similarly to insulin, and thus has the ability to lower blood sugar. Growth hormone elevates your blood sugar when levels are too low. However, increased amounts of growth hormone can inhibit insulin effects, leading to too high of blood sugar levels (6).

With regards to obesity, growth hormone levels are much lower than normal. However, calorie restriction and consequent weight loss are associated with normalized growth hormone release. Some data shows that synthetic growth hormone treatment may improve metabolism in obese individuals that are also undergoing calorie restriction, representing a potential obesity therapy (7).

Sex hormones and obesity

Certain sex hormones play a role in how body fat is distributed, meaning that these hormones may contribute to obesity. Oestrogens and androgens are sex hormones that have several roles in the body, one of which is dictating body fat distribution. Oestrogens, for example, are produced in the ovaries of pre-menopausal women and are key to the ovulation phase of a woman’s menstrual cycle.

Both men and post-menopausal women produce lower levels of oestrogen. In contrast to pre-menopausal women who produce it in their ovaries, men and post-menopausal women create oestrogen within their body fat. These levels are lower with age, causing changes to how body fat appears. For example, pre-menopausal women typically carry their fat in the lower body, while post-menopausal women and men carry fat in the abdomen area. Additionally, some data suggests that lower oestrogen levels contribute to weight gain.

Because of the interplay between sex hormones and body fat, sex hormones may influence one’s development of obesity and related diseases such as stroke, heart disease, and arthritis. When body fat is stored in the abdominal area, such as with older age, this increases your risk for these diseases. Research shows, though, that post-menopausal women that receive oestrogen do not accumulate abdominal fat (8).

Conclusion

Obesity is a very prevalent condition, and though very common, predisposes you to a slew of health issues. The effects of obesity are widespread, contributing to diseases such as diabetes, high blood pressure, high cholesterol, stroke, and more. The impending threat of these risks causes many to wonder how and why obesity occurs.

The answer is not as simple as a poor diet and minimal exercise. Our endocrine system plays a key role in producing hormones that regulate bodily functions that contribute to satiety, fat distribution, and metabolism. Knowing the mechanisms underly hormones such as leptin, insulin, growth hormone, and sex hormones can help you understand how your endocrine system influences your behavior and risk of obesity.

References

1. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
2. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/endocrine-system
3. https://www.news-medical.net/health/Obesity-and-Hormones.aspx
4. https://my.clevelandclinic.org/health/articles/22446-leptin
5. https://obesitymedicine.org/obesity-and-insulin-resistance/
6. https://my.clevelandclinic.org/health/articles/23309-human-growth-hormone-hgh
7. https://pubmed.ncbi.nlm.nih.gov/10193871/
8. https://www.betterhealth.vic.gov.au/health/healthyliving/obesity-and-hormones#obesity-and-sex-hormones

Author

David J. Bauder, PA-C David Bauder, PA-C, is a certified physician assistant and the assistant medical director at Weight Loss and Vitality in Manassas and Alexandria, Virginia, Washington, DC; and Gaithersburg, MD. He enjoys helping patients optimize their physical and mental health to improve their overall well-being. He earned his physician assistant degree from the University of Texas Health Science Center at San Antonio. Afterward, he gained admission into the reputable graduate program for physician assistant studies at the University of Nebraska Health Science Center in Omaha. David has over 26 years of experience working as a physician assistant. He’s practiced in podiatry, family medicine, emergency medicine, general surgery, urgent care, and functional medicine.