The 5 Most Important Hormones for Weight Loss

Each year, millions of Americans try to lose weight. If you’ve been there, you know how hard the process can be. You probably also know that food choices and activity level are major factors in weight loss. But how much do you know about the role of hormones?

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Hormones are your body’s chemical messengers, and you have more than 50 of them. They deliver messages to your cells, instructing them to start or stop doing certain actions in order to help regulate all sorts of bodily processes. Sometimes, however, hormone levels get a little off balance, and having too much or too little of a hormone can lead to symptoms and health issues. 

Numerous hormones affect body weight, specifically by regulating appetite. On the flip side, changes in weight can influence hormone functioning. Here’s an overview of five to understand if you’re trying to lose weight or keep weight off.

1. Ghrelin 

Nicknamed “the hunger hormone,” ghrelin stimulates your appetite by telling your brain it’s time to eat. Ghrelin levels peak when you’re in a state of fasting, such as when you wake up, and they fall as you eat.

Ghrelin contributes to the difficulty of sustained weight loss. Levels of the hormone increase when you lose weight — it’s a metabolic adaptation to prevent starvation. You’ll feel hungrier if you reach a lower-than-typical weight because your body wants to get you back to your starting weight. Ghrelin also activates reward and motivation centers in the brain, which can trigger pleasant feelings. This might push you to snack or go back for seconds even when you’re not hungry, which can lead to overeating and weight gain. 

2. Leptin

Leptin is a satiety hormone produced by adipocytes, or fat cells. When you eat, your stomach releases leptin into the bloodstream, which then travels to your brain. Leptin’s main job is to help control your energy balance by signaling to your brain that you’re full.

Though leptin is basically the opposite of ghrelin, it might similarly contribute to weight regain after weight loss attempts: When you lose weight, you lose fat mass. This causes leptin levels to decrease because leptin is produced by fat cells. Lower leptin levels lead to increased hunger, making it hard to keep weight off.

Obesity is a state of leptin resistance, which means that you produce more leptin but the leptin receptors in your brain don’t properly respond to the hormone’s signals. So, while your brain should recognize that you're full, it mistakenly believes you’re in a low-energy fasting state. Your appetite then increases despite having high levels of leptin.

3. Insulin 

Insulin regulates your blood glucose (sugar) levels. After eating, your pancreas releases insulin to help move glucose from your bloodstream into your cells. Then, your cells use glucose as their energy source. 

Your cells can become resistant to insulin’s effects, causing hyperinsulinemia, a condition characterized by high levels of insulin in your blood. With hyperinsulinemia, fat, muscle and liver cells do not efficiently take up or store glucose from your blood. Experts believe that hyperinsulinemia may alter how your brain receives leptin signals, leading to an increased appetite when you should feel full. Overall, elevated insulin levels can lead to weight gain.  

Having excess weight is a major risk factor for developing insulin resistance. Untreated insulin resistance can lead to pre-diabetes and Type 2 diabetes. This is why obesity specialists might recommend lifestyle changes or medication, or both, to treat insulin resistance, even if a patient’s blood work doesn’t indicate it.

4. GLP-1

GLP-1, short for glucagon-like peptide-1, is a gut-related hormone secreted from intestinal cells when you eat. GLP-1’s primary role is to help manage blood sugar levels and aid in digestion. Even though GLP-1 is released in your intestines, it doesn’t stay there. It travels through your bloodstream and binds to receptors all over your body and brain.

GLP-1 works to regulate appetite in many ways, but the three main ones are:

  • Slowing down digestion, making you feel fuller for longer 
  • Supporting glucose-dependent insulin secretion, which means your pancreas secretes the right amount of insulin based on the amount of glucose in your food
  • Binding to receptors in your brain to suppress appetite

Some research supports the idea that people with obesity have impaired GLP-1 signaling. GLP-1 agonist medications such as Ozempic and Wegovy (which have the same active ingredient, semaglutide) promote weight loss by mimicking the effects of the GLP-1 hormone.

5. Cortisol

Cortisol, produced by the adrenal glands, is often called the “stress hormone.” Cortisol levels are typically highest in the early morning and lowest at night, but they can rise and fall throughout the day in response to stressors. Chronic stress can lead to high cortisol levels. This can disrupt the balance of appetite-regulating hormones such as leptin and ghrelin, influencing how much and often you eat.

Cortisol also slows down insulin production and increases the amount of glucose your liver makes. Both of these actions increase blood sugar levels. The purpose is to give you energy (glucose) so you can stay alert to deal with stressful situations. But, as a result, research shows that high cortisol levels can spur cravings for foods high in fat and sugar, and can also increase feelings of satisfaction from eating these foods.

Navigating imbalances

Achieving and maintaining a healthy weight is always beneficial for health. If you have obesity, losing 5% of your total body weight can lead to measurable improvements in weight-related comorbidities such as insulin resistance. But weight loss itself might not fix most hormonal imbalances associated with obesity. Leptin resistance is one example. Although leptin levels decline when you lose weight, your brain is unable to receive leptin’s signals for various reasons.

If you have obesity and are trying to lose weight, appetite-regulating hormones can compound the challenges of reaching and staying at your goal weight. In response to weight loss, ghrelin, leptin, insulin and GLP-1, among other hormones not discussed in this article, change in ways that increase hunger and fat storage. These are compensatory physiological mechanisms designed to keep your weight at its “set” point. That’s not to suggest you should give up, but rather to reinforce the idea that obesity is a chronic disease and managing it effectively might require more than willpower and/or lifestyle changes alone. It also explains the common scenario of dieting and exercising but not being able to lose weight. An obesity specialist can evaluate your health history and recommend an optimal weight-loss plan based on your needs. 

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References

  • Nogueiras R. Mechanisms in Endocrinology: The gut-brain axis: regulating energy balance independent of food intake. Eur J Endocrinol. 2021;185(3):R75-R91. doi:10.1530/EJE-21-0277
  • Martin C, Herrick K, Sarafrazi N, Ogden C. Attempts to Lose Weight among Adults in the Key Findings Data from the National Health and Nutrition Examination Survey.; 2018. Accessed August 8, 2023. https://www.cdc.gov/nchs/data/databriefs/db313.pdf#:~:text=In%202013%E2%80%932016%2C%2049.1%25%20of%20U.S.%20adults%20tried%20
  • US EPA. Overview of the Endocrine System. www.epa.gov. Published July 6, 2015. Accessed August 8, 2023. https://www.epa.gov/endocrine-disruption/overview-endocrine-system
  • Farhadipour M, Depoortere I. The Function of Gastrointestinal Hormones in Obesity-Implications for the Regulation of Energy Intake. Nutrients. 2021;13(6):1839. doi: 10.3390/nu13061839
  • Gruzdeva O, Borodkina D, Uchasova E, Dyleva Y, Barbarash O. Leptin resistance: underlying mechanisms and diagnosis. Diabetes Metab Syndr Obes. 2019;12:191-198. doi: 10.2147/DMSO.S182406
  • Lustig RH, Collier D, Kassotis C, Roepke TA, Kim MJ, Blanc E, et al. Obesity I: Overview and molecular and biochemical mechanisms. Biochem Pharmacol. 2022;199:115012. doi: 10.1016/j.bcp.2022.115012
  • Roh E, Choi KM. Hormonal Gut-Brain Signaling for the Treatment of Obesity. Int J Mol Sci. 2023;24(4):3384. doi: 10.3390/ijms24043384
  • Herhaus B, Ullmann E, Chrousos G, Petrowski K. High/low cortisol reactivity and food intake in people with obesity and healthy weight. Transl Psychiatry. 2020;10(1):40. doi: 10.1038/s41398-020-0729-6
  • Chao AM, Jastreboff AM, White MA, Grilo CM, Sinha R. Stress, cortisol, and other appetite-related hormones: Prospective prediction of 6-month changes in food cravings and weight. Obesity (Silver Spring). 2017;25(4):713-720. doi: 10.1002/oby.21790

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