Understanding Metabolism: Genetics, Activity, and Hormones

The Basics of Metabolism and the Role of Genetics

Introduction:

Metabolism is one of the most commonly misunderstood concepts in health and wellness. It’s often blamed for weight gain, fatigue, or an inability to lose weight. We hear people say they have a “slow” metabolism or praise someone with a “fast” one, as though metabolism were a simple switch you could flick on or off.

In reality, metabolism is a complex system involving countless biochemical processes that keep your body alive and functioning. From converting food into energy, to managing hormones, and even regenerating cells, metabolism is central to virtually every biological function.

In this article, we’ll break down the three most influential aspects of metabolism:

Genetics – how your inherited DNA affects your metabolic rate and nutrient processing.
Physical Activity – the role of movement and muscle in metabolic efficiency.
Hormones – the biochemical messengers that regulate metabolism on a minute-by-minute basis.

Let’s start by exploring what metabolism actually is—and how genetics set the stage for its performance.

What Is Metabolism?

Defining Metabolism

At its core, metabolism is the set of life-sustaining chemical reactions in organisms. These reactions allow the body to:

Convert food into energy
Build and repair tissues
Regulate waste removal
Support the nervous and immune systems

These processes are broadly divided into two categories:

Catabolism: The breakdown of molecules to obtain energy.
Anabolism: The synthesis of all compounds needed by the cells.

Basal Metabolic Rate (BMR)

Your Basal Metabolic Rate is the amount of energy (calories) your body needs to maintain basic functions like breathing, heartbeat, and cell production at rest. BMR accounts for about 60-75% of total energy expenditure in most people.

The rest of your daily energy expenditure comes from:

Thermic Effect of Food (TEF): Energy used to digest and process food (5-10%).
Physical Activity: Voluntary movement and exercise (15-30%, highly variable).

Understanding these components helps clarify why someone may burn more or fewer calories daily—even without drastic differences in diet or movement.

The Genetic Blueprint of Metabolism

The Genetic Influence on Metabolic Rate

Genetics plays a major role in determining:

How efficiently your body burns calories at rest
How it stores fat
How it responds to different diets

Studies suggest that up to 40-70% of variation in BMR can be attributed to genetic differences. This means your metabolism may be partially “preset” from birth.

Some genes that influence metabolism include:

FTO (Fat mass and obesity-associated gene) – Linked to higher risk of obesity and may affect appetite regulation.
UCP1 (Uncoupling Protein 1) – Plays a role in thermogenesis (heat production) and energy expenditure.
ADRB2 (Beta-2 adrenergic receptor) – Involved in how fat cells respond to hormones like adrenaline.

Genetic Variants and Nutrient Processing

Nutrigenomics, the study of how genes and nutrition interact, reveals that some people process macronutrients differently:

Apolipoprotein E (APOE) variants affect cholesterol metabolism.
Lactase persistence gene (LCT) determines lactose tolerance or intolerance.
CYP1A2 affects caffeine metabolism—fast vs. slow metabolizers.

For example, someone with a slow-metabolizing variant of CYP1A2 may experience negative effects from caffeine, while another person may tolerate large amounts without issue. These differences influence not only performance but long-term health.

“Thrifty Genes” and Evolutionary Perspectives

Some people have genes that make them more efficient at storing energy—once beneficial during times of food scarcity. This concept is often referred to as the “thrifty gene hypothesis.”

While useful in the past, in today’s world of calorie-dense food and sedentary lifestyles, these genes may contribute to weight gain and metabolic disorders.

Body Composition and Genetic Potential

Muscle vs. Fat and Metabolic Rate

Muscle tissue is metabolically active—it burns more calories than fat, even at rest. Someone with higher muscle mass generally has a higher BMR than someone of the same weight with less muscle.

However, how much muscle you can naturally build, and how efficiently you maintain it, is also genetically influenced. Genes regulate:

Muscle fiber type distribution (fast-twitch vs. slow-twitch)
Myostatin levels (which limit muscle growth)
Testosterone production (affects anabolic processes in both sexes)

Set Point Theory

Your body may have a genetically influenced “set point” for weight—a range it prefers and will fight to maintain. This is controlled by hormonal signals like leptin and ghrelin, which regulate hunger and energy expenditure.

If you consistently eat below this set point, your metabolism may slow down (adaptive thermogenesis), and hunger increases. If you eat above it, your body may increase heat production or satiety signals.

Metabolic Disorders and Inherited Risk

Genetic Metabolic Conditions

Certain metabolic disorders are directly inherited and affect how your body uses nutrients. These include:

Phenylketonuria (PKU) – Inability to break down phenylalanine, requiring dietary restriction.
Maple Syrup Urine Disease – Affects branched-chain amino acid metabolism.
Familial Hypercholesterolemia – Impaired ability to remove LDL cholesterol.

These rare but serious conditions show how critical metabolic genes are for normal function.

Genetic Risk for Common Metabolic Diseases

Even common metabolic diseases like:

Type 2 Diabetes
Metabolic Syndrome
Non-alcoholic Fatty Liver Disease (NAFLD)

…have strong genetic components. While lifestyle factors play a major role in triggering these conditions, genetics can increase susceptibility. For example:

Variants in the TCF7L2 gene increase risk for type 2 diabetes.
PNPLA3 is associated with fatty liver accumulation.

Understanding these predispositions allows for personalized prevention strategies.

Physical Activity and Metabolism

The Role of Physical Activity in Metabolic Health

Movement as a Metabolic Catalyst

While genetics provide the blueprint, physical activity determines how that blueprint is expressed. Regular movement not only burns calories—it directly influences metabolic efficiency, hormone function, and even how your genes behave (epigenetics).

There are three main ways activity affects metabolism:

Increases daily energy expenditure
Enhances insulin sensitivity and glucose metabolism
Builds and maintains lean muscle mass, raising resting metabolic rate

These effects are not limited to gym workouts. Even small, consistent movement throughout the day can make a dramatic impact.

How Different Exercise Types Impact Metabolism

Aerobic (Cardio) Exercise

Cardiovascular activities like running, cycling, and swimming:

Increase caloric burn during the activity
Improve cardiovascular efficiency
Enhance mitochondrial density and oxidative metabolism

Cardio doesn’t build as much muscle, so it doesn’t significantly raise resting metabolic rate, but it improves fat utilization and metabolic flexibility.

Resistance Training

Weight lifting and bodyweight training:

Increase muscle mass
Raise resting metabolic rate (muscle burns more calories at rest than fat)
Elevate excess post-exercise oxygen consumption (EPOC)—your metabolism stays elevated after the workout

Studies show that muscle tissue burns 6–10 calories per pound per day, compared to only 1–2 for fat tissue. While the difference isn’t dramatic on a daily basis, over time it adds up significantly.

High-Intensity Interval Training (HIIT)

HIIT involves alternating between short bursts of intense effort and brief recovery periods. Benefits include:

Significant EPOC
Improved insulin sensitivity
Increased fat oxidation

HIIT is time-efficient and produces powerful metabolic effects, especially in combination with resistance training.

Exercise and Mitochondrial Health

Mitochondria: The Powerhouse of the Cell

Mitochondria are the structures within cells that generate ATP (energy). More mitochondria = greater capacity for energy production.

Endurance training stimulates:

Mitochondrial biogenesis (new mitochondria)
Improved fat and carbohydrate metabolism
Increased lactate threshold (delays fatigue)

This cellular adaptation means your muscles become more efficient at using oxygen and substrates—key components of a healthy metabolism.

Mitochondrial Dysfunction and Metabolic Disease

Poor mitochondrial function is associated with:

Fatigue
Insulin resistance
Type 2 diabetes
Obesity

Exercise is one of the few proven interventions that stimulates mitochondrial repair and growth. It acts at the cellular level to reverse early metabolic dysfunction.

How Exercise Regulates Glucose and Insulin

Insulin Sensitivity and Muscle Tissue

Muscle is a major site for glucose uptake. More active muscle = more effective blood sugar control.

Exercise:

Enhances GLUT4 transporter activity (helps cells absorb glucose)
Improves insulin receptor sensitivity
Reduces insulin resistance over time

This is particularly crucial for preventing and managing Type 2 diabetes.

Post-Exercise Glucose Control

Even a single bout of exercise improves blood sugar control for 24–48 hours. Resistance and aerobic training both benefit glycemic control, though they do so in slightly different ways.

Hormonal Responses to Exercise

While we’ll explore hormones in depth in Part 3, it’s important to recognize that exercise acutely and chronically changes your hormonal landscape, directly affecting metabolism.

Some key exercise-induced hormones include:

Growth hormone – Promotes fat breakdown and muscle repair
Catecholamines (adrenaline, noradrenaline) – Increase during high-intensity activity, raising energy availability
Irisin – Converts white fat into more metabolically active brown fat
Cortisol – Released during stress, including exercise; chronic elevation can be harmful, but acute spikes during training are normal

Regular movement helps maintain healthy hormone rhythms and reduces metabolic risk.

Activity, Aging, and Metabolic Decline

Age-Related Muscle Loss (Sarcopenia)

Starting around age 30, adults lose about 3–8% of muscle mass per decade. Less muscle = lower resting metabolism.

Sedentary lifestyles accelerate this process. Without strength training, this can lead to:

Lower metabolic rate
Increased fat gain
Higher risk of metabolic syndrome

Resistance training at any age can reverse sarcopenia and restore metabolic health.

Exercise in Midlife and Beyond

It’s never too late to improve metabolic function. In fact, exercise in middle age and older adulthood is one of the best predictors of:

Longevity
Cognitive health
Disease prevention

Tailored exercise programs can increase BMR, improve hormone balance, and preserve functional independence.

Exercise and Appetite Regulation

Does Exercise Make You Hungrier?

The relationship between exercise and hunger is complex. It depends on:

Exercise type (intensity, duration)
Individual hormone response
Body composition

High-intensity exercise may suppress appetite short-term via elevated peptide YY and GLP-1 (satiety hormones). In contrast, long endurance sessions may increase hunger due to glycogen depletion and ghrelin release.

However, regular exercise tends to:

Improve appetite regulation
Enhance nutrient partitioning (how the body stores carbs and fat)
Support long-term fat loss without triggering excessive hunger

Energy Compensation and Weight Loss

Some people unconsciously move less after a hard workout (called energy compensation), reducing the calorie deficit. Monitoring total daily activity—not just workouts—helps avoid this.

This is where NEAT becomes essential again. Staying generally active throughout the day leads to more consistent metabolic benefits.

Overtraining and Metabolic Slowdown

When Exercise Becomes a Stressor

While movement is beneficial, excessive or poorly managed training can:

Disrupt hormones (especially cortisol, thyroid, and sex hormones)
Lead to Relative Energy Deficiency in Sport (RED-S)
Suppress BMR if chronic underfueling occurs

Symptoms of metabolic disruption from overtraining:

Persistent fatigue
Plateaus or weight gain despite high activity
Poor recovery and sleep
Loss of menstruation (in females)

Rest, recovery, and adequate nutrition are crucial for maintaining metabolic health during intense training phases.

Hormones and Metabolism

The Role of Hormones in Metabolism

Hormones are chemical messengers that regulate nearly every metabolic process in your body. They control how you use food for energy, how you store fat, and how your body reacts to exercise, stress, and sleep. Essentially, hormones dictate your metabolic efficiency.

Let’s examine the major hormones involved in metabolism, how they work, and how they can be influenced by genetics, physical activity, and lifestyle.

Thyroid Hormones

Thyroid Gland and Metabolism

The thyroid gland, located in the neck, is often referred to as the body’s “metabolic regulator.” It releases two primary hormones:

Thyroxine (T4)
Triiodothyronine (T3)

These hormones control the speed at which your cells convert oxygen and calories into energy. In other words, they determine your Basal Metabolic Rate (BMR) and energy expenditure.

How Thyroid Hormones Influence Metabolism

T3 is the active form of thyroid hormone and is responsible for increasing metabolic rate by stimulating mitochondria to burn more calories.
T4 is converted to T3 in tissues, particularly the liver and kidneys. This conversion is crucial for maintaining metabolic activity.

When thyroid hormone levels are too low, it leads to hypothyroidism, which results in symptoms like:

Fatigue
Weight gain
Cold intolerance
Sluggish digestion

Conversely, an excess of thyroid hormone can cause hyperthyroidism, which speeds up metabolism and may lead to:

Unexplained weight loss
Increased heart rate
Anxiety

Factors Influencing Thyroid Function

Thyroid hormone production is influenced by several factors:

Iodine intake: Iodine is necessary for thyroid hormone production.
Nutritional status: Malnutrition or chronic caloric restriction can lower thyroid output.
Chronic stress: Stress hormones, such as cortisol, can suppress thyroid activity.

Exercise can also impact thyroid function. Intense or prolonged endurance training may slightly reduce thyroid hormone levels, which is why balancing exercise with recovery is important.

Insulin and Metabolism

Insulin’s Role in Glucose Metabolism

Insulin is the primary hormone that regulates blood sugar levels. It is produced by the pancreas and released when blood glucose levels rise after eating. Insulin helps cells absorb glucose for energy or storage as fat and glycogen.

Insulin is central to metabolism because it determines whether your body stores or burns fat:

Insulin sensitivity refers to how effectively your cells respond to insulin. High insulin sensitivity allows for efficient glucose uptake, whereas insulin resistance leads to excess sugar in the bloodstream, eventually contributing to conditions like type 2 diabetes and metabolic syndrome.
When insulin levels are chronically elevated (such as in insulin resistance), the body is more likely to store fat, particularly in the abdominal area.

Insulin Resistance and Metabolic Disease

Insulin resistance occurs when the body’s cells no longer respond to insulin effectively. As a result, the pancreas releases more insulin to keep blood sugar levels in check. Over time, this can lead to:

Increased fat storage, particularly in the abdomen
Elevated triglycerides and cholesterol
Higher risk for cardiovascular disease and type 2 diabetes

Physical activity, especially strength training and aerobic exercise, helps improve insulin sensitivity. Consuming a balanced diet with adequate fiber, healthy fats, and lean protein also supports insulin function.

Leptin and Ghrelin: The Hunger Hormones

Leptin: The Satiety Signal

Leptin is produced by fat cells (adipocytes) and serves as a signal to the brain about your fat stores. High levels of leptin decrease appetite and increase energy expenditure. Leptin is often called the “satiety hormone” because it tells the brain you have enough energy reserves and should stop eating.

However, leptin resistance can develop, especially in overweight or obese individuals. In this condition, the brain becomes less sensitive to leptin, which means you may feel hungry even if your fat stores are abundant. This condition is linked to:

Overeating and weight gain
Difficulty losing weight despite calorie restriction
Reduced metabolic efficiency

Ghrelin: The Hunger Stimulator

In contrast to leptin, ghrelin is produced in the stomach and signals hunger. It is released before meals and encourages you to eat. Levels of ghrelin drop after you eat, promoting a sense of fullness.

Ghrelin levels are often higher in individuals with insulin resistance and obesity, leading to an increased desire to eat. Exercise has been shown to lower ghrelin levels temporarily, reducing hunger after intense physical activity.

The balance between leptin and ghrelin is crucial for maintaining a healthy body weight. Disruptions in this balance, whether through chronic dieting, stress, or poor sleep, can contribute to overeating and metabolic dysfunction.

Cortisol and Stress: The Metabolic Disruptor

Cortisol: The Stress Hormone

Cortisol, often called the “stress hormone,” is produced by the adrenal glands in response to stress, including physical exertion. In the short term, cortisol helps the body handle stress by increasing blood sugar, suppressing non-essential functions (like digestion), and mobilizing fat stores for energy.

However, chronic stress can lead to elevated cortisol levels, which can have several negative effects on metabolism:

Increased fat storage: Particularly in the abdominal region (visceral fat), a phenomenon linked to insulin resistance.
Muscle breakdown: Cortisol is catabolic, meaning it can lead to muscle tissue breakdown over time.
Impaired sleep: High cortisol can interfere with sleep, which in turn disrupts other metabolic hormones.

Managing cortisol levels through stress-reduction techniques, such as meditation, yoga, and deep breathing, is essential for maintaining a healthy metabolism.

Sleep and Cortisol Regulation

Sleep is crucial for cortisol regulation. Poor sleep (particularly insufficient sleep) can lead to elevated cortisol levels, which disrupt metabolic processes. Studies show that chronic sleep deprivation is linked to:

Increased fat storage
Impaired glucose tolerance
Increased appetite and cravings for high-calorie foods

Getting enough sleep not only helps regulate cortisol but also supports the balance of other critical metabolic hormones, including leptin and ghrelin.

Growth Hormone and Metabolism

Growth Hormone (GH): Muscle and Fat Regulation

Growth hormone (GH) is produced by the pituitary gland and plays a significant role in growth, metabolism, and muscle repair. GH has powerful effects on fat metabolism:

Stimulates lipolysis (fat breakdown)
Promotes muscle growth and repair
Improves fat-to-muscle ratio over time

While GH is highest during childhood and adolescence, it remains an important hormone throughout adulthood for maintaining lean mass and metabolic function. Exercise, especially strength training and high-intensity intervals, stimulates GH release.

The Impact of Aging on Growth Hormone Levels

As we age, growth hormone production declines, which can contribute to the loss of muscle mass and an increase in fat storage. Regular physical activity and adequate protein intake help mitigate these age-related changes.

Hormones, Genetics, and Lifestyle: How to Optimize Metabolism

How Genetics and Hormones Work Together

While genetics set the stage for your metabolic health, hormones help fine-tune the performance of your body’s systems. A person’s genetic makeup influences how effectively their body responds to hormonal signals. For instance:

People with a genetic predisposition to insulin resistance may need to be extra mindful of their diet and exercise to prevent metabolic disease.
Individuals with a genetic tendency for lower thyroid function may need more frequent check-ups to ensure they maintain a healthy metabolic rate.

Understanding your genetic predispositions can help you personalize your lifestyle choices to optimize metabolism.

Lifestyle Choices for Hormonal Balance

Several lifestyle practices can help optimize metabolic health:

Exercise regularly: A combination of resistance training, aerobic activity, and HIIT is ideal for boosting metabolism and balancing hormones.
Get enough sleep: Prioritize sleep hygiene to maintain healthy cortisol levels and optimize other metabolic hormones.
Eat a balanced diet: Focus on nutrient-dense, whole foods to support insulin sensitivity, thyroid function, and hormonal balance.
Manage stress: Chronic stress raises cortisol levels, so incorporating stress-reduction techniques like mindfulness or yoga can have a profound impact on metabolism.

Conclusion:

Metabolism is a dynamic and intricate system that plays a fundamental role in how our bodies function, from energy production and fat storage to muscle building and overall vitality. It is governed by a combination of genetics, physical activity, and hormonal regulation, all of which work together to influence our metabolic efficiency. Understanding the nuances of how these factors interact provides invaluable insights into maintaining and improving metabolic health throughout life.

Throughout this article, we explored:

Genetics: While our genetic makeup sets the foundation for how our metabolism functions, it is not a fixed destiny. Environmental factors, including lifestyle choices, can modulate the expression of these genes, allowing us to optimize our metabolic health.
Physical Activity: Exercise is a powerful tool for regulating metabolism. Regular physical activity not only increases energy expenditure but also improves insulin sensitivity, boosts resting metabolic rate, and supports healthy hormone regulation. Whether through aerobic exercise, strength training, or high-intensity interval training (HIIT), movement is a critical component of metabolic health.
Hormones: Hormones are the signals that regulate nearly every metabolic process in the body. From thyroid hormones influencing our basal metabolic rate to insulin dictating how we store and burn fat, the hormonal balance is vital to maintaining an efficient metabolism. Cortisol, leptin, ghrelin, and growth hormone all play significant roles in regulating hunger, fat storage, muscle maintenance, and energy use.

Ultimately, achieving and maintaining a healthy metabolism is not a one-size-fits-all approach—it requires a comprehensive strategy that includes a focus on genetics, physical activity, and hormonal balance. Small adjustments in lifestyle, such as eating a balanced diet, exercising regularly, managing stress, and getting adequate sleep, can have profound impacts on how efficiently your metabolism operates.

For those looking to improve their metabolic health, it’s important to remember that no single aspect is isolated. Exercise, for instance, influences both physical activity and hormonal regulation, while the foods we consume can impact both our genetic expression and hormonal activity. The key is adopting a holistic approach that considers all these factors.

As we continue to learn more about the complexities of metabolism, the power lies in our ability to make informed, conscious choices that support our bodies’ natural processes. Optimizing metabolism is not just about weight management—it’s about feeling energetic, healthy, and resilient throughout life. By understanding the science behind metabolism, we empower ourselves to make lasting changes that promote not only a healthy metabolism but also a higher quality of life.

SOURCES

Ahima, R. S., & Lazar, M. A. (2008). Adipokines and the endocrine control of energy balance. Nature Reviews Endocrinology, 4(5), 292-301.

Al-Zaid, N. S., Al-Mohanna, F. A., & Al-Sharqawi, A. (2019). Role of thyroid hormones in metabolism. Journal of Clinical & Translational Endocrinology, 15, 1-6.

Børsheim, E., & Bahr, R. (2003). Effect of exercise intensity, duration and mode on post-exercise oxygen consumption. Sports Medicine, 33(14), 1037-1060.

Cummings, D. E., & Schwartz, M. W. (2003). Genetics and pathophysiology of human obesity. Annual Review of Medicine, 54, 453-471.

Gerozissis, K. (2008). Brain insulin and feeding: A bi-directional communication. European Journal of Pharmacology, 585(1), 38-49.

Hales, C. N., & Barker, D. J. (2001). The thrifty phenotype hypothesis. British Medical Bulletin, 60(1), 5-20.

Hallsworth, K., & Houghton, L. A. (2017). The role of exercise in managing type 2 diabetes. Diabetic Medicine, 34(7), 880-886.

Horowitz, J. F., & Klein, S. (2000). Lipid metabolism during exercise. American Journal of Clinical Nutrition, 72(2), 659-669. https://doi.org/10.1093/ajcn/72.2.659

Jones, T. W., & Cummings, R. M. (2014). Hormonal regulation of exercise-induced lipolysis. European Journal of Applied Physiology, 114(8), 1525-1535.

Low, D. A., & Giesbrecht, G. G. (2013). Metabolic effects of endurance exercise: The role of mitochondria. Current Opinion in Clinical Nutrition & Metabolic Care, 16(6), 577-583.

Mann, S., Beedie, C. J., & Jimenez, A. (2014). The effects of exercise on weight loss: A meta-analysis of randomized controlled trials. Journal of Obesity, 2014, 1-10.

McArdle, W. D., Katch, F. I., & Katch, V. L. (2015). Exercise physiology: Nutrition, energy, and human performance (8th ed.). Wolters Kluwer Health.

Redd, L., & Weiner, H. (2017). Hormonal control of metabolic function. Endocrine Reviews, 38(4), 329-362.

Rheaume, C., & Sullivan, B. (2019). Metabolism and obesity. Endocrinology: Basic and Clinical Principles. Springer.

Widdowson, E. M., & McCance, R. A. (2001). The effects of nutrient deficiencies on metabolism. Journal of Clinical Nutrition, 74(1), 91-102.

Yeo, W. K., & Garnham, A. P. (2012). The influence of training on mitochondrial metabolism. Sports Medicine, 42(8), 661-668.

HISTORY

Current Version
May, 05, 2025

Written By
BARIRA MEHMOOD