Obesity and Appetite Regulation

Overview of Obesity

• Obesity is a complex chronic disease characterized by dysfunctional or excess body fat (adiposity) that impairs health.
• Individual differences in body composition, body fat distribution, and function impact the threshold at which adiposity impairs health.
• Causes of obesity are complex, resulting from genetic, biological, behavioral, psychosocial, and environmental factors interacting.

Learning Outcomes

• Learning Outcome 1: Define obesity.
• Learning Outcome 2: Recognize obesity as a chronic disease.
• Learning Outcome 3: Explain the pathophysiology of obesity.
• Learning Outcome 4: List the complications of obesity.
• Learning Outcome 5: Outline the overarching principles of investigation and management of obesity complications.
• Learning Outcome 6: Outline different approaches to weight loss.

Obesity Definition

• Obesity is a complex chronic disease characterized by dysfunctional or excess body fat (adiposity), impairing health.
• Individual variations in body composition, fat distribution, and function lead to variability in the impact of adiposity on health, making a precise threshold challenging to establish.
• Causes of obesity arise from interactions between genetic, biological, behavioral, psychosocial, and environmental factors.

Body Mass Index (BMI)

• BMI calculates weight in kilograms divided by height in meters squared (kg/m²).
• Historically, a BMI over 30 kg/m² defines obesity and over 25 kg/m² defines overweight.
• BMI is used in epidemiological studies, to risk stratify individuals, and is an indicator for screening weight-related health risks.
• BMI is not a definitive tool for identifying adiposity-related complications in individuals. It should be used alongside other screening and assessment measures.

Epidemiology

• Worldwide obesity has tripled since 1975.
• In 2016, over 1.9 billion adults were overweight, with more than 650 million having obesity.
• Approximately 39% of adults aged 18 and older were overweight in 2016; 13% had obesity.
• Obesity prevalence in Ireland in 2016 was 21.0% and 35% were overweight.
• Bahrain had a 36.9% obesity prevalence and 35.5% were overweight in 2016.
• Over 340 million children and adolescents (5-19 years old) were either overweight or obese in 2016.

Can You Have a High BMI and Be Healthy?

• A statistically significant relationship exists between increasing BMI levels and health risks.
• However, individuals with high BMIs might not exhibit relevant health issues, demonstrating considerable variability.

At What Point Does Adiposity Impair Health?

• Health complications emerge at an individual level due to the mass, location, and distribution of adiposity.
• Genetic predispositions and health disparities influence how adiposity impacts health.
• There's no universal threshold; the effect of adiposity on health depends on individual factors.

Learning Outcome 2: Obesity is a Chronic Disease

• The American Medical Association classified obesity as a disease in 2013.
• Obesity is strongly associated with substantial morbidity and premature death, often exhibiting a progressive nature similar to diabetes or hypertension.
• Obesity encompasses more than dietary intake and physical activity, impacting the amount and distribution of adiposity, even when diet and exercise remain consistent.
• Bodies' responses defend against weight loss in a process recognized as the “starvation response.” This highlights the lifelong nature of obesity and the need to shift focus away from weight loss to encompass overall well-being.

Learning Outcome 3: Obesity Pathophysiology

• The brain plays a crucial role in obesity and energy balance.
• The brain can be divided into three main areas regulating weight: hypothalamus (homeostatic area), mesolimbic system (hedonic area), and frontal lobe (executive functioning).

Physiology Summary

• Appetite (hunger/satiety), energy expenditure, and peripheral signals are interconnected in obesity.
• Gut hormones (Ghrelin, CCK, GLP-1, OXM, PYY, Amylin, Leptin, Insulin) influence food intake and energy balance.
• Adipocytes release hormones (Leptin, Adiponectin) that regulate appetite and metabolism.
• The arcuate nucleus within the hypothalamus plays a key role in regulating food intake and expenditure. Neuropeptides in the arcuate nucleus and paraventricular nucleus regulate these functions.

Hypothalamus (Homeostatic Area)

• Hormonal and neural signals from the gut, adipose tissue, and peripheral hormones activate hunger-related neurons like AgRP and NPY in the arcuate nucleus.
• This process stimulates feelings of hunger.
• Paraventricular neurons and melanocortin system (especially MCR-4) play a major role in suppressing the signals of hunger.
• These signaling systems are altered in cases of obesity.

Mesolimbic System (Hedonic Area)—Reward and Cravings

• The emotional aspects of eating (pleasure and reward) are central to the mesolimbic system.
• Hedonic eating involves enjoyment and craving driven by reward (e.g., dopamine, opioid, and endocannabinoid pathways).
• Food craving can persist even after satiation.
• Heightened food anticipation (wanting) and dopamine issues can lead to overeating.

Frontal Lobe (Executive Functioning)

• The prefrontal cortex directs behaviours related to executive function; overriding primal behaviours like cravings.
• Cognitive function requires optimal rest, adequate oxygenation, and stress reduction for optimal performance.
• Medications (steroids) and substance abuse negatively impact connections between the frontal lobe and other brain regions, interfering with the control of eating behaviour.

Set Point

• In states of decreased fat stores, circulating leptin and insulin levels fall, and the hypothalamus triggers a compensatory response to initiate feeding.
• This lowers inhibitory effects on AgRP and NPY neurons to increase appetite and diminish energy expenditure.
• Increasing body adiposity triggers an increase in circulating leptin, providing a negative feedback loop that results in suppressing appetite.

Hormonal Adaptation to Weight Loss

• Weight regain is common after initial weight loss due to hormonal counter-regulatory adaptations.
• Weight loss produces changes in hormones—increasing appetite-stimulating hormones (like Ghrelin) while lowering appetite-suppressing hormones—contributing to weight regains.

Genetics and Obesity

• Obesity is highly heritable.
• Monogenic and polygenic factors influence obesity risk.
• Single gene mutations (rare) or combinations of many genes (polygenic) contribute to varying degrees of obesity predisposition.
• Environmental factors and populations' dietary behaviours contribute to the diversity seen in obesity rates.

Learning Outcome 4: Complications of Obesity

• Obesity is associated with multiple medical complications, including pulmonary disease, sleep apnea, and hypoventilation syndrome.
• Other complications include pancreatitis, non-alcoholic fatty liver disease (NAFLD), cirrhosis, gallbladder disease, and multiple types of cancers (breast, uterus, colon).
• Cardiovascular complications like coronary heart disease, diabetes, dyslipidemia, hypertension, and stroke are significant concerns.
• Gynecological issues such as irregular menstrual cycles, infertility, and polycystic ovarian syndrome are related to obesity.
• Other obesity-related complications include osteoarthritis, phlebitis, skin conditions (e.g., gout, venous stasis), and psychological factors.

Learning Outcome 5: Investigation and Management of Obesity Complications

• Obesity-centered history and physical exam, including anthropometric measurements (e.g., weight, height, waist circumference) and blood pressure are crucial for assessing obesity complications.
• Metabolic investigations like blood work are utilized to evaluate potential underlying causes and associated risks.

History

• Obesity-centered history should include detailed medical, surgical, and family history, including relevant medications, allergies, and social/lifestyle information.
• An emphasis should be made on the underlying causes, including hypothyroidism, Cushing's syndrome, sleep disorders, eating patterns, and past weight loss attempts.
• Questions about physical activity, stress levels, and mood should be part of the evaluation.

Exam

• Baseline anthropometric measurements and other relevant assessments, look for complications (e.g., blood pressure with appropriate cuff size, sleep apnea (OSA), cardiovascular, gastrointestinal, musculoskeletal and skin assessments)
• Endocrine evaluation should rule out alternative causes of weight gain such as Cushing's disease or hypothyroidism.

Investigations for Complications

• Investigations are dictated by symptoms, risk factors and clinical signs (Metabolic profile – HbA1c, lipids, liver function tests, thyroid tests, urinalysis, blood counts, vitamin and nutrient levels).
• Assessment should include OSA screening.
• Suspicion of Cushing’s requires further investigation.

Learning Outcome 6: Approaches to Weight Loss

• Weight loss management should not solely focus on the weight number but rather involve the individual's best weight and overall well-being.
• A holistic approach to weight management should consider adequate nutrition, improvement in cardiorespiratory reserve, mobility, self-esteem and quality of life.
• Interventions should include medical nutrition therapy (involving a dietitian), physical activity, and consideration of psychological intervention.
• Considerations may include pharmacotherapy and possibly bariatric surgery in certain cases.

Medical Nutrition

• Obesity management shouldn't adhere to a single eating pattern; personalized approaches emphasizing individual eating patterns, food quality, and a positive relationship with food are imperative.
• Caloric restriction alone tends not to be sustainable long-term.
• Individuals with obesity have heightened risk of micronutrient deficiencies, including vitamin D, B12, and iron.

Medical Nutrition Therapy

• Patient-centered approaches, such as utilizing the Irish healthy eating guidelines (e.g., adequacy of vegetables, protein, and whole grains, and encouraging water consumption over other beverages), are important considerations in managing obesity.
• Additional support from a registered dietitian or obesity management specialists might be warranted depending on the individual's needs.

Physical Activity

• Consistent physical activity, regardless of weight, benefits health.
• Includes aerobic and resistance exercise, promoting cardio-respiratory fitness, mobility, strength and muscle mass.
• Physical activity can be negatively affected by other treatments, such as calorie restriction, medications, and bariatric surgery.
• Addressing weight bias and stigma are critical for encouraging engagement in physical activity.
• Body weight gain with age necessitates consideration for physical activity strategies, such as maintaining lean tissue, and reducing metabolic impact of higher fat mass in older adults.

Psychology and Behavioral Interventions

• Realistic and achievable goals within a supportive environment
• Behaviour-change strategies may address underlying psychological, medical, or activity issues encountered by individuals with obesity.
• Psychological interventions (cognitive behavioural therapy, acceptance and commitment therapy, and compassion-focused therapies) may benefit individuals with obesity.
• Understanding motivations, behaviours, environmental triggers, and barriers related to weight management is critical to successful interventions.

Indications for Anti-Obesity Medications

• Medication use is indicated for BMI ≥ 30 kg/m² (obesity) or BMI ≥ 27 kg/m².
• It can be co-morbid with other conditions and is approved as an adjunct to diet and exercise.

Benefits of Combined Treatment (Pharmacotherapy and Lifestyle Modification)—Additive Effects

• Pharmacotherapy and lifestyle modification approaches work additively.
• Pharmacotherapy, by modifying inner environmental aspects such as hunger cues and food preoccupation, can aid in weight loss.
• Lifestyle modification impacts external environmental factors, reducing access to food and promoting cues for restraint/physical activity.

Pharmacotherapy

• Multiple medications are available as anti-obesity treatments; their mechanism and FDA approval timeframe vary.
• These agents act on different targets within the body to effectively curb excessive weight gain.

Bariatric Surgery

• Indicated for individuals above the age of 18 with a BMI greater than or equal to 35 kg/m² having at least one major adiposity-related complication, BMI over 40 kg/m² (regardless of complications), or BMI 30-34.9 kg/m² with refractory non-surgical weight loss and related complications (T2DM).
• Includes techniques like gastric bypass, sleeve gastrectomy, and adjustable gastric banding (different methods and surgical procedures).

Outcomes from Bariatric Surgery

• Weight loss, resolution of T2DM (type 2 diabetes) and hypertension, and sleep apnea are potential outcomes.
• Associated risks and adverse events such as dysphagia, vomiting, dumping syndrome, band intolerance, weight regain, gastroesophageal reflux, and Barrett's esophagus should be considered.

Benefits of Weight Loss

• Weight loss shows significant positive effects on several metabolic health indicators like prediabetes to diabetes progression, improving lipids and blood pressure, improving outcomes in instances of NASH, and reducing the index of apnea hypopnea/improving respiratory health.

Key Points

• Obesity is a chronic and complex disease characterized by excess body fat.
• BMI is not a definitive measurement for assessing adiposity-related health issues.
• The multifaceted nature necessitates a long-term, individualised approach encompassing lifestyle changes (nutrition, physical activity, and psychological support) rather than a singular focus on numbers on a scale.
• Individuals experiencing obesity confront increased stigma and bias; a shift in healthcare narratives that addresses those issues is required.

Key Points (Continued)

• The brain and hormonal signals play a central role in regulating energy homeostasis, appetite, and executive control in obesity.
• Genetic predisposition and sustained environmental influences play critical roles in obesity development.
• The treatment approach must move beyond simple prevention tactics to include dietetics, physical activity, behavioral modification, psychology, pharmacotherapy and bariatric surgery.

Resources

• Multiple resources exist concerning clinical guidelines, the association for the study of obesity in Ireland, Canada, and globally, and other relevant information on obesity.