The Science Behind Obesity and Weight Loss Materials

THE WEIGHT OF THE MATTER: UNDERSTANDING THE SCIENCE BEHIND OBESITY AND WEIGHT LOSS

Faculty:

L. Austin Fredrickson, MD, FACP

L. Austin Fredrickson, MD, FACP, is an Associate Professor of Internal Medicine at Northeast Ohio Medical University, where he serves as core faculty and teaches diagnostics, therapeutics, clinical skills, and health humanities. He is board-certified in general internal medicine and practices rural primary care.

Susan Bowlin, DNP, FNP-BC, ACNP-BC, CBN

Dr. Susan Bowlin, DNP, FNP-BC, ACNP-BC, CBN, is a double-board certified nurse practitioner with over 25 years of experience in family practice, acute care, and obesity medicine. She is the founder of Priority One Weight Loss, where she specializes in evidence-based obesity care, empowering patients to achieve sustainable health and vitality. Dr. Bowlin holds a Certificate of Advanced Education in Obesity Medicine. She is a national speaker and educator on cardiometabolic disease and a founding member and treasurer of the Dallas Obesity Society. An active leader in her field, Dr. Bowlin is dedicated to transforming lives through compassionate care, patient-centered solutions, and innovative treatment modalities.

Liz Fredrickson, PharmD, BCPS

Liz Fredrickson is an Associate Professor of Pharmacy Practice and Pharmaceutical Sciences at the Northeast Ohio Medical University (NEOMED) College of Pharmacy.

Pamela Sardo, PharmD, BS

Pamela Sardo is a freelance medical writer, pharmacist licensed in 2 states, and the founder/principal at Sardo Solutions. She received her BS from the University of Connecticut and a PharmD from the University of Rhode Island. Pam’s career spans many years in retail, clinics, hospitals, long-term care, Veterans Affairs, pharmaceutical manufacturing, and managed healthcare across broad therapeutic classes and disease states.

Topic Overview:

Obesity is a chronic and complex disease that requires a long-term, multifaceted approach to treatment. “Overweight” and “obese” statuses occur when the accumulation of excess fat increases a patient’s risk for poor health outcomes. Healthcare professionals assess a patient’s weight circumference and/or body mass index (BMI) as estimates of body fat when diagnosing obesity. Obesity has been linked to numerous problematic health-related outcomes, including the development and worsening of diseases, increased healthcare costs, and diminished quality of life. Given its significant health

impacts, patients should be encouraged to approach it as a lifelong condition requiring ongoing management rather than viewing weight loss as merely a short-term goal. Several factors, including genetics, behavior, socioeconomic conditions, and epigenetics, influence the pathophysiology of obesity. Understanding the underlying mechanisms of obesity is essential for healthcare professionals to develop effective treatment strategies and deliver patient-centered care. This course will describe the classification of obesity and explore its epidemiology, etiology, and pathophysiology, and learners will gain insight into the biological and environmental factors driving obesity. This educational activity will also emphasize the importance of a collaborative care approach to obesity management.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-25-037-H01-P

Pharmacy Technician  0669-0000-25-038-H01-T

Credits: 1.5 contact hour(s) (0.15 CEU(s)) of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $5.99

Estimated time to complete activity: 1.5 contact hour(s) (0.15 CEU(s)), including Course Test and course evaluation

Release Date: April 2, 2025 Expiration Date: April 2, 2028

Target Audience: This educational activity is for pharmacists and pharmacy technicians.

Secondary Audiences: Other healthcare professionals, such as nurses, physicians, or others who may be part of a healthcare team, may be interested in this educational topic. A healthcare team approach to patient care may be discussed in this activity, as applicable. No state board or professional organization has evaluated this activity to determine whether it meets the

continuing education requirements of nurses, physicians, or other professions not listed under the “Target Audience” described above. Always verify with individual employers or supervisors whether they will accept this educational activity upon completion.

How to Earn Credit: From April 2, 2025, through April 2, 2025, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “Educational Activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Recall the classification of obesity according to body mass index

Describe factors that influence the pathophysiology of obesity

Describe metabolic adaptation and its role in obesity management

Explain the epidemiology and etiology of obesity, highlighting trends and contributing factors in diverse patient populations

Disclosures

The following individuals were involved in developing this activity: L. Austin Fredrickson, MD, FACP, Liz Fredrickson, PharmD, BCPS, Susan Bowlin, DNP, FNP-BC, ACNP-BC, CBN, and Pamela Sardo, PharmD, BS. Austin Frederickson, Liz Frederickson, and Pamela Sardo have no conflict of interest or financial relationship or commercial or financial support relevant to this activity to report or disclose in the development of this activity.

Disclosure: Susan Bowlin is a member of the Speaker’s Bureau for Eli Lilly and Novo Nordisk.

© RxCe.com LLC 2025: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity

The Weight of the Matter: Understanding the Science Behind Obesity and Weight Loss

Introduction

Obesity is a chronic and complex disease that requires a long-term, multifaceted approach to treatment. Understanding the risk factors of obesity and its underlying mechanisms is essential for healthcare professionals to develop effective treatment strategies and deliver patient-centered care. This course will discuss other medical conditions associated with obesity, describe the classification and pathophysiology of obesity, and provide insight into the biological and environmental factors driving this condition. This educational activity will also emphasize the importance of a collaborative care approach to obesity management.

Definitions and Classification of Obesity

Understanding the classification of obesity and related terminology will assist healthcare professionals in navigating relevant guidelines, studies, and treatment recommendations.1,2 “Overweight” and “obese” statuses occur when the accumulation of excess fat increases a patient’s risk for poor health outcomes.2 Importantly, this definition does not imply that a patient has an obesity-related condition, just that they are at an increased risk for one.2

Societal views of body weight can stigmatize people with obesity. This is known as “weight stigma.”3,4 This can lead to social devaluation or discrimination of people who are obese. This stigma can impede weight loss maintenance since these patients may be too embarrassed to seek professional help.4 Healthcare teams can help mitigate this stigma by using first-person language when discussing obesity with patients, such as “patient with obesity” or “patient with BMI of 33” rather than “an obese patient.”3

Body Mass Index (BMI) as a Metric

Numerous methods are available to determine obesity status, including dual-energy X-ray absorptiometry (DEXA) scanning, computed tomography (CT), and magnetic resonance imaging (MRI) to measure body fat adiposity. Unfortunately, due to associated costs and time, these methods are impractical for healthcare professionals to use daily. More typically, healthcare professionals will utilize waist circumference and/or body mass index (BMI) as estimates of body fat. These metrics have their limitations but are more practical for everyday use.

Body mass index is calculated as weight in kilograms divided by the square of height in meters (kg/m2), and it provides a standardized way to compare weights across populations, independent of height (Table 1).2 While BMI generally correlates well with body fat percentage, this relationship can vary based on factors such as sex, age, race, and increased lean muscle mass, particularly in individuals such as bodybuilders.2

Table 1 BMI Categories2

Limitations of BMI as a Metric

While still a widely used metric, BMI has notable limitations that reduce its effectiveness as a comprehensive health measure.4,5 It does not account for body fat distribution, such as harmful abdominal fat, often leading to the misclassification of muscular or larger-boned individuals.4,5 Furthermore, BMI provides no insight into the origins or variability of obesity and its outcomes within individuals or populations.4,5 Although simple and useful for screening, BMI can mislead healthcare professionals by only approximately estimating adiposity when no assessment of functional health, fitness, or the specific health risks associated with fat distribution is also conducted.4,5 Body mass index also fails to predict disease risk adequately, as physical fitness can sometimes outweigh BMI’s implications.4,5

Studies show that patients who are classified as "overweight" but who are fit may have better mortality outcomes than lean but unfit individuals, emphasizing the need to consider fitness and fat distribution, like abdominal fat, which are stronger predictors of health risks than BMI alone.4,5 Reports from the American Medical Association (AMA) highlight these limitations and advocate for more nuanced assessments beyond BMI.4,5

Conditions Associated with Obesity

Obesity has been linked to numerous problematic health-related outcomes. Conditions associated with obesity include the development and worsening of diseases, increased healthcare costs, and diminished quality of life.1 Given the significant health impacts of obesity, patients should be encouraged to approach it as a lifelong condition requiring ongoing management rather than viewing weight loss as merely a short-term goal.

Conditions associated with obesity are listed in Table 2 below.

Table 2

Conditions Associated with Obesity1

Epidemiology of Obesity

Obesity has reached epidemic proportions globally, with prevalence rates rising significantly in recent decades. A 2024 report from the Centers for Disease Control and Prevention (CDC) provides insight into the prevalence of obesity among United States (US) adults between August 2021 and August 2023.6 During this period, the overall obesity prevalence was 40.3%, with similar rates among men (39.2%) and women (41.3%).6 Obesity prevalence varied significantly by age group, with rates highest among adults aged 40–

59 (46.4%), compared to 35.5% in those aged 20–39 and 38.9% in those aged 60 and older. Severe obesity was present in 9.4% of adults, with women experiencing a higher prevalence (12.1%) compared to men (6.7%).6

Looking at trends over time—from 2013–2014 to 2021–2023—overall obesity rates remained relatively stable. However, the prevalence of severe obesity increased notably from 7.7% to 9.7%.6

Etiology of Obesity

Broadly, obesity manifests when there is an imbalance between energy intake and expenditure.1 However, research supports the etiology of obesity as multifactorial, involving complex interactions between genetic, behavioral, environmental, and social determinants.1,7,8

Genetic Influences

Genetics significantly impact the development of obesity as well as fat distribution, with genetic factors contributing between 40–50% of the variance in BMI and body fat.1 Numerous studies have found that changes in gene expression, polymorphisms, and genetic mutations all play a role in making individuals more prone to developing obesity.9

Genetic obesity is categorized into three types: monogenic, polygenic, and syndromic.9 Monogenic obesity, a rare but severe form, arises from mutations in a single gene and is characterized by hyperphagia (insatiable hunger) and early-onset obesity, typically between ages 3 and 5.9 Polygenic obesity is more common and results from the cumulative effects of multiple gene variants.9 Syndromic obesity is associated with developmental disorders and is often accompanied by dysmorphic features and organ abnormalities and may occur as part of syndromes like Prader-Willi, Cohen, and Bardet- Biedl.9

Examples of genes associated with obesity are presented in Table 3 below.9

Table 3

Genes Associated with Obesity9

Behavioral Factors

Behavioral factors play a significant role in the development of obesity, influenced by intrinsic mechanisms and external environmental changes. Physical inactivity is a key contributor to the development of obesity, yet it remains a global challenge for patients.9 According to a 2016 World Health Organization survey, over 28% of adults and 81% of adolescents were

physically inactive.7 Contributing factors include sedentary employment and technological advances that encourage screen-based recreation.9

Excessive caloric intake is another critical factor, traditionally explained by the energy balance model (EBM) of obesity, which attributes weight gain to an imbalance between calories consumed and expended.9 However, alternative theories have challenged this model, such as the carbohydrate- insulin model (CIM), which suggests that diets high in refined carbohydrates and sugars trigger postprandial hyperinsulinemia.9 This process shifts calories into fat storage, reducing metabolic rates and increasing hunger, perpetuating a cycle of weight gain.9

Environmental Factors

Modern societal and technological advancements have created an "obesogenic" environment that promotes weight gain.1 The increased availability of calorie-dense, low-cost, and heavily marketed foods, combined with sedentary lifestyles and reduced physical activity, have aided in rising obesity rates.1 Social networks, cultural norms, and socioeconomic status also influence obesity risk, with individuals more likely to become obese if close friends or family members are affected.1 Additionally, changes in gut microorganisms and insufficient sleep also contribute to obesity.1

Medical Conditions and Medications

Certain medical conditions can make patients more prone to developing obesity, including Cushing's syndrome, growth hormone deficiency, insulinoma, leptin deficiency, and psychiatric disorders like depression and binge-eating disorder.1 While hypothyroidism is often considered, it primarily causes fluid retention and not true obesity.1 Clinicians should conduct thorough evaluations to identify potential secondary causes.1 Additionally, numerous medications are associated with unintended weight gain, including antiseizure drugs (carbamazepine, gabapentin), antidepressants (mirtazapine, tricyclic antidepressants, desvenlafaxine), antipsychotics (olanzapine, risperidone), and hormones (corticosteroids, insulin), among

others.1 Pharmacists can play an essential role in recognizing those who can develop obesity and provide proactive interventions. (See Table 4.)

Table 4 Pharmacist Interventions

Socioeconomic Factors

Emerging evidence suggests a growing prevalence of obesity in low- and middle-income countries, driven by urbanization, dietary changes, and reduced physical activity.7 Socioeconomic status (SES) and minority status influence the prevalence, outcomes, and treatment challenges surrounding obesity.7 Obesity disproportionately affects individuals from lower SES backgrounds, and these risks are often linked to limited access to education, healthier food options, and recreational opportunities.7 Psychosocial stress, neighborhood poverty, and food insecurity further exacerbate obesity risks in low-income and minority communities.7 These populations also face barriers to effective treatment, including limited access to healthcare, high attrition in obesity trials, and challenges related to childcare, costs, and transportation.7 These additional contributors to obesity are summarized in Table 5.9

Table 5

Risk Factors for Obesity9

Addressing Socioeconomic Factors

To address these challenges effectively, interprofessional collaboration and competency in obesity care are crucial. Teams composed of diverse healthcare professionals, including physicians, nurses, pharmacists, dietitians, social workers, and behavioral health professionals, can leverage the unique expertise of each discipline to address the multifaceted nature of obesity. Interprofessional communication, shared decision-making, and cultural humility are vital for building patient trust, particularly in underserved populations. Recognizing and respecting the diverse cultural and socioeconomic factors influencing health behaviors ensures that interventions

are tailored to the individual’s context. Collaborative care models may improve access to treatment and enhance patient adherence and outcomes by addressing obesity as a chronic, multifactorial condition.8 Such approaches will be essential to mitigate the disparities in obesity prevalence and outcomes and to reduce the overall societal and economic burden of this global health crisis.

Pathophysiology of Obesity

The pathophysiology of obesity involves dysregulation of energy balance and metabolic processes.1,2 Genetics, behavior, socioeconomic conditions, and epigenetics influence this pathophysiology.1,2

The pathophysiology of obesity involves an intricate interplay between neural, hormonal, and environmental factors that regulate appetite, energy balance, and fat storage. Numerous receptors and hormones are involved in these processes (Table 6).1 Understanding these mechanisms allows healthcare teams to better assist patients in managing obesity and tailoring therapeutic interventions.

Table 6

Effects of Neurotransmitters and Receptors of Food Intake1

Appetite Regulation

Appetite is orchestrated by a complex neural network involving the hypothalamus, limbic system, brainstem, hippocampus, and cortex.1 Neurotransmitters like serotonin, norepinephrine, dopamine, neuropeptide Y (NPY), and α-melanocyte-stimulating hormone (α-MSH) play pivotal roles.1 NPY is the most powerful stimulator of eating, while α-MSH acts as an inhibitor through its interaction with melanocortin receptors.1 The lateral hypothalamus, often called the "hunger center," utilizes orexin and melanocyte-concentrating hormone (MCH) to drive hunger signals.1 Beyond hunger, these peptides influence other physiological processes, highlighting the interconnected nature of brain functions.1

Peripheral Signals Influencing Appetite

Peripheral signals heavily influence the brain’s appetite regulation.1 Hormones such as leptin, which is secreted by adipose tissue, act on the hypothalamus to suppress appetite and increase energy expenditure.1 In most individuals with obesity, leptin resistance occurs, diminishing its effectiveness.1 Other important hormones include ghrelin, which stimulates appetite, and gut hormones like glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and oxyntomodulin, which suppresses food intake. These signals form a feedback loop, connecting the brain, gut, and adipose tissue to modulate energy intake.1

Energy Balance

Obesity results from a chronic imbalance between energy intake and expenditure. Resting energy expenditure (REE), which includes basal metabolic rate (BMR), accounts for most of the body’s energy usage.1 Physical activity significantly influences total energy expenditure.1 The thermogenic effect of food—a temporary increase in metabolic rate after eating—also contributes to energy usage.1

The process of fat storage is also important. It involves two types of adipose tissue: white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates heat through mitochondrial activity.1 BAT is more prevalent in lean individuals and has a potential, although unclear, role in human obesity management.1 WAT and BAT are innervated by the sympathetic nervous system, and β-adrenergic receptor stimulation promotes fat breakdown and energy expenditure.1

Metabolic Adaptation and Weight Management

One of the most challenging aspects of obesity management is overcoming metabolic adaptation, a phenomenon where the body resists sustained weight loss by reducing energy expenditure.10 This adaptive process is rooted in evolutionary survival mechanisms and can persist long after weight loss, making weight maintenance difficult.10 During energy deficits, the body reduces energy expenditure and increases hunger, counteracting weight loss efforts.10 The key components of metabolic adaptation include a decline in REE and non-exercise activity thermogenesis (NEAT), which involves energy spent on non-exercise activities.10 Hormonal changes also play a significant role; leptin levels drop with fat loss, reducing satiety signals, while ghrelin increases, increasing the feeling of hunger.10

Personalized and Sustainable Weight Management Strategies

These adaptations highlight the need for personalized and sustainable weight management strategies.10 Rapid weight loss often exacerbates these

effects, leading to increased hunger and decreased energy expenditure, while focusing on gradual, controlled weight loss can mitigate these responses by preserving lean body mass (a key determinant of REE).10 Healthcare professionals should be aware of strategies to combat metabolic adaptation. These include eating high-protein diets (1.2–2 g/kg body weight), which help maintain lean mass and reduce hunger, and incorporating sufficient quantities of dietary fiber to promote satiety and support gut health.10 Intermittent energy restriction (IER), such as diet breaks or refeeds, can also provide patients with psychological and physiological relief by mitigating prolonged energy deficits.10 Additionally, patients can be counseled to incorporate resistance training to preserve lean mass further and increase energy expenditure.10 By addressing the physiological, behavioral, and psychological aspects of weight management, collaborative care teams can help patients achieve sustainable weight loss and minimize the effects of metabolic adaptation, ultimately improving long-term outcomes.10

Collaborative Obesity Management

The management of obesity is significantly influenced by the approach healthcare professionals take toward patients with this condition.9 A compassionate, nonjudgmental attitude is critical in addressing the complex needs of individuals with obesity, particularly as the stigma surrounding weight can have profound mental and physical health consequences.4,9 Weight bias often equates obesity with negative traits such as laziness, low intelligence, poor hygiene, and lack of willpower.9 This stigma not only can worsen a patient’s self-esteem but also discourages individuals from seeking medical advice, continuing the cycle of poor health outcomes.

To effectively address the multifaceted contributors to obesity, a multidisciplinary approach is essential.9 Involving a diverse team of providers is crucial to help tackle barriers to care, such as addressing psychosocial stressors, enhancing access to resources, and tailoring interventions to individual needs.9 Additionally, promoting empathy, education, and inclusivity within healthcare settings is critical to removing weight stigma and creating sustainable, patient-centered solutions to obesity management.9

Summary

Obesity is a chronic and complex disease that requires a long-term, multifaceted approach to treatment. Several factors, including genetics, behavior, socioeconomic conditions, and epigenetics, influence the pathophysiology of obesity. While BMI is still a widely used metric to determine obesity, it has notable limitations that reduce its effectiveness as a comprehensive health measure. It does not account for body fat distribution, such as harmful abdominal fat, often leading to the misclassification of muscular or larger-boned individuals. Patients should be encouraged to treat obesity as a lifelong condition rather than view weight loss as a short-term goal.

Course Test

What is the BMI range for Class 2 obesity?

18.5–24.9

25.0–29.9

35.0–39.9

≥40

How is severe obesity defined by BMI?

≥30

35.0–39.9

≥40

18.5–24.9

Which method is most commonly used in clinical practice to classify obesity due to its practicality?

BMI

DEXA scanning

MRI

CT scans

What hormone secreted by adipose tissue helps suppress appetite and increase energy expenditure?

Ghrelin

Leptin

Insulin

GLP-1

Which neurotransmitter is the most potent stimulator of eating?

α-MSH

Serotonin

Dopamine

Neuropeptide Y (NPY)

Which region of the brain is commonly referred to as the "hunger center"?

Brainstem

Arcuate nucleus

Paraventricular nucleus

Lateral hypothalamus

What is metabolic adaptation?

The increase in energy expenditure during weight loss

The physiological response to energy restriction that reduces energy expenditure

The process of increasing fat storage during dieting

A hormonal increase that boosts satiety

What hormonal change occurs during metabolic adaptation that increases hunger?

Decrease in ghrelin

Increase in ghrelin

Increase in leptin

Decrease in cortisol

According to the CDC, which age group has the highest prevalence of obesity?

Adults aged 40–59

Adults aged 20–39

Adults aged 60 and older

Adolescents aged 12–21

What is the genetic contribution to BMI and body fat variance?

10–20%

30–40%

40–50%

60–70%

References

Sheehan A, Chen JT, Yanovski JA. Obesity. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw Hill; 2023.

Purnell JQ. Definitions, Classification, and Epidemiology of Obesity. [Updated 2023 May 4]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Accessed March 31, 2025. https://www.ncbi.nlm.nih.gov/books/NBK279167/

National Institute of Diabetes and Digestive and Kidney Diseases. Weight Management for Health Professionals. Talking with Your Patients about Weight. NIH-NIDDK. August 2023. Accessed March 31, 2025. https://www.niddk.nih.gov/health-information/professionals/clinical- tools-patient-management/weight-management/talking-with-your- patients-about- weight#:~:text=Use%20person%2Dfirst%20language&text=It%20can

%20be%20used%20to,instead%20of%20%E2%80%9Cobese%20peopl e.%E2%80%9D

Wu Y, Li D, Vermund SH. Advantages and Limitations of the Body Mass Index (BMI) to Assess Adult Obesity. Int J Environ Res Public Health. 2024;21(6):757. Published 2024 Jun 10. doi:10.3390/ijerph21060757

Rubino F, Cummings DE, Eckel RH, et al. Definition and diagnostic criteria of clinical obesity [published correction appears in Lancet Diabetes Endocrinol. 2025 Mar;13(3):e6. doi: 10.1016/S2213- 8587(25)00006-3.]. Lancet Diabetes Endocrinol. 2025;13(3):221-262. doi:10.1016/S2213-8587(24)00316-4

Emmerich SD, Fryar CD, Stierman B, Ogden CL. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021-August 2023. NCHS Data Brief. 2024;(508):10.15620/cdc/159281.

doi:10.15620/cdc/159281

Anekwe CV, Jarrell AR, Townsend MJ, Gaudier GI, Hiserodt JM, Stanford FC. Socioeconomics of Obesity. Curr Obes Rep. 2020;9(3):272-279. doi:10.1007/s13679-020-00398-7

Eliot K, et al. Interprofessional obesity treatment: an exploration of current literature and practice. J Interprof Educ Pract. 2021;25(10): 100475.doi:10.1016/j.xjep.2021.100475

Masood B, Moorthy M. Causes of obesity: a review. Clin Med (Lond).

2023;23(4):284-291. doi:10.7861/clinmed.2023-0168

Martínez-Gómez MG, Roberts BM. Metabolic Adaptations to Weight Loss: A Brief Review. J Strength Cond Res. 2022;36(10):2970-2981. doi:10.1519/JSC.0000000000003991

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