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Primer on Obesity and Medical Weight Management Pt III. When the Metabolic Dance Goes Offbeat: Unraveling the Impact on Weight Management

Updated: Jun 12

In part II of this blog series, we explored the harmonious dance of ghrelin, leptin, and insulin in managing your energy, hunger, and weight. In part III, let's discuss what happens when this intricate choreography between ghrelin, leptin, insulin, and incretins encounters an imbalance and how it can sway the balance of weight management.

The Metabolic Dance: When there's harmony

In our previous discussions, we explored how ghrelin signals hunger, while leptin triggers the sensation of satiety and fullness. Insulin expertly guides glucose out of the bloodstream and into different cells where it is either used immediately as energy or stored as fat for later use. Finally, we briefly discussed the role of incretins. These peptides, produced in the small intestine, play various supporting roles in the metabolic dance—they enhance insulin secretion, influence brain function, slow gastric emptying, and tell the liver to decrease glucose production and increase glucose storage. Ghrelin, leptin, insulin, and incretins, along with many other hormones and peptides, work together to create a harmonious dance that regulates appetite and energy balance.


Imbalance in the Dance: What happens when it doesn't run smoothly?

Let's take a closer look at how an imbalance may disrupt the entire performance.

Persistent Hunger Pangs -- Ghrelin is off

Ghrelin is the hormone produced in the stomach that signals hunger to the brain, typically increasing between meals. However, ghrelin levels can also rise due to reduced calorie intake, lack of sleep, stress, and irregular eating patterns. These factors signal the body to protect its energy stores and resist weight loss, increasing hunger and potentially leading to overeating even when energy stores are sufficient.

Difficulty in Feeling Full -- Leptin is off

Leptin is the satiety hormone, produced by fat cells, that tells the brain and body to stop consuming energy because there is enough stored. As fat mass increases, so do leptin levels; conversely, as fat mass decreases, leptin levels fall. Leptin resistance can occur when, despite high levels of leptin, the brain does not respond properly, resulting in continued hunger and reduced energy expenditure. Overconsumption of high-calorie, processed foods and chronic inflammation, often seen in obesity, can desensitize leptin receptors, disrupting the fullness signal.

Blood Sugar Rollercoaster (Insulin and Incretins Imbalance)

Insulin resistance occurs when cells in the muscles, fat, and liver do not respond effectively to insulin, making it difficult for glucose to enter cells, leading to hyperglycemia and increasing the risk of diabetes. Factors such as obesity, physical inactivity, diets high in sugar and unhealthy fats, genetic predisposition, hormonal imbalances, and chronic stress contribute to insulin resistance. In response to persistent high blood sugar, the pancreas produces more insulin, but the ineffective response leads to a vicious cycle of high insulin levels promoting fat storage and inhibiting fat breakdown, causing weight gain.

Incretins, affected by factors such as poor gut health and inadequate nutrient intake, play a crucial role in enhancing insulin performance and regulating appetite. Inadequate incretin function disrupts digestive processes, nutrient absorption, and satiety signaling, potentially leading to overeating and weight gain.

A Real-Life Scenario -- Illustrating the imbalance

Imagine increased stress has disrupted your sleep for the last two months due to a big project at work. You are working longer hours, skipping gym workouts, and eating irregularly at your desk. To compensate for the lack of exercise, you skip lunch and have minimal meals, resulting in lightheadedness and difficulty focusing, despite losing about 10 pounds. You think, "This is a nice bonus. Maybe I can keep this weight loss up after the project ends..." But you know you can't because you are constantly hungry. What's happening?

Increased stress, disrupted sleep, irregular eating habits, and decreased caloric intake lead to increased ghrelin levels, signaling increased hunger. Diets high in sugar, refined carbohydrates, and unhealthy fats, combined with physical inactivity, contribute to insulin resistance and hyperglycemia. Weight loss leads to decreased leptin levels, reducing satiety signals and increasing hunger.

Understanding that this "metabolic dance" is an intricate network of signals between organs, hormones, peptides, and mechanisms is crucial in realizing that maintaining a healthy body weight and energy balance is far more complex than simply "eat less, exercise more." In the next blog post, we will illustrate this with a more concrete example, discussing the well-known TV show "The Biggest Loser."


Dr. Cardona is board certified in family medicine and obesity medicine and is the founder and physician owner of Cardona Direct Primary Care and RefineMD Aesthetics. Currently accepting new patients. (904) 551-4625. Visit for information on our obesity management services.

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