Obesity, Hunger and Eating Behaviors

• Obesity is defined as a complex chronic disease characterized by dysfunctional or excess body fat (adiposity) that impairs health.
• Individual differences in body composition, fat distribution, and function mean the threshold at which adiposity impairs health varies among adults.
• The causes of obesity are complex and result from interactions between genetic, biological, behavioral, psychosocial, and environmental factors.
• BMI (Body Mass Index) is calculated as weight in kilograms divided by height in meters squared (kg/m²).
• Historically, obesity has been defined using a BMI cutoff >30 kg/m², while overweight is defined as a BMI >25 kg/m².
• Health complications increase as BMI increases at the population level, so it is used to risk stratify and screen for weight-related health risks.
• BMI is not an accurate standalone tool, and should be used with other methods to identify adiposity-related complications in individuals.
• Worldwide obesity has nearly tripled since 1975.
• In 2016, >1.9 billion adults were overweight, of whom >650 million had obesity.
• 39% of adults aged ≥18 were overweight in 2016, and 13% had obesity.
• Obesity prevalence in Ireland is 21.0%, with 35% overweight.
• Obesity prevalence in Bahrain is 36.9%, with 35.5% overweight.
• Over 340 million children and adolescents aged 5-19 worldwide are overweight or have obesity.
• Individuals can present with no health issues over a wide range of BMIs, despite having high BMIs.
• Health complications occur because of the mass, location, and distribution of adiposity, as well as genetics and health inequalities.
• There's no "one size fits all approach" because of the threshold varies.
• The American Medical Association designated obesity as a disease in 2013.
• Obesity is associated with substantial burden of morbidity and premature death.
• Obesity is a chronic and often progressive disease, similar to diabetes or high blood pressure.
• Adiposity amount or distribution vary widely with the same diet and exercise,
• Obesity is a lifelong process as the body defends against weight loss with a "starvation response"
• Prioritize overall health and wellbeing over solely weight loss.
• Obesity is a heritable neurobehavioral disorder strongly influenced by environmental factors.
• Twin studies show a 50-80% concordance in BMI and regional adiposity, regardless of environment.
• Environmental factors of obesity are inexpensive processed foods and beverages, sugar, sleep loss, urbanization and health equalities
• The brain likely plays the most important role in obesity and energy balance.
• Three brain areas regulate weight: the hypothalamus (homeostatic area), the mesolimbic system (hedonic area), and the frontal lobe (executive functioning).
• The hypothalamus (homeostatic area) governs homeostatic (hunger) drives and inhibits food intake when energy balance is achieved.
• Hormone and neural signals from the gut, adipose tissue, and peripheral hormones stimulate neurons expressing AgRP and NPY in the arcuate nucleus to stimulate hunger.
• These neurons work on the paraventricular neuron (PVC) via melanocortin 4 (MCR 4) to stimulate eating and this activity decreases rapidly after eating
• AgRP/NPY neurons project to the second set of neurons co-expressing pro-opiomelanocortin (POMC) & cocaine and amphetamine-regulated transcript (CART), which suppress food intake through the downstream inhibitory Y1 and gamma-aminobutyric acid (GABA) receptors
• Normally these are in balance with each other, and is dysregulated in disease.
• Peripheral signals regulate appetite and energy expenditure.
• Gut hormones such as Ghrelin, CCK, GLP-1, OXM, and PYY send appetite signals from the stomach and intestines to the brain.
• Adipocyte hormones like Amylin and Leptin send appetite signals from fat cells to the brain.
• Insulin sends signals from the Pancreas to the brain
• Ghrelin is the only circulating orexigenic (hunger-increasing) hormone.
• Ghrelin is secreted by the gastric fundus and proximal small intestine.
• Ghrelin stimulates gut motility, decreases insulin secretion, increases food intake, increases energy balance, and increases weight gain.
• Ghrelin peaks before meals and drops after meals.
• Increased ghrelin causing hyperphagia and severe obesity is a sign of Prader-Willi Syndrome.
• Hormones that increase food intake are orexogenic, and hormones that decrease food intake are anorexigenic
• The chart below shows peripheral effect depending on which site the hormone synthesis from
  • Ghrelin from the stomach, increases food intake
  • Cholecystokinin (CCK) from the Intestinal L-cells in duodenum & jejunum, decreases food intake.
  • Glucagon-like peptide-1 (GLP-1) from the Intestinal L-cells in distal small bowel & colon, decreases food intake.
  • Oxytomodulin (OXM) from the Intestinal L-cells in distal small bowel & colon, decreases food intake.
  • Peptide YY (PYY) from the Intestinal L-cells in distal small bowel, colon, & rectum, decreases food intake.
• Adipocyte tissue secretes hormones and cytokines regulating weight, insulin sensitization, and inflammation.
  • Leptin - Weight loss, fullness, satiety
  • Adiponectin - Insulin Sensitization
  • Inflammatory Cytokines (IL6, TNF, etc) - Inflammation
• Leptin is secreted by white adipose tissue adipocytes.
• Leptin stimulates the anorexigenic neuron system in the hypothalamus.
• Leptin inhibits the orexigenic neuron system in the hypothalamus.
• Leptin decreases appetite, increases thermogenesis, and reduces fat mass.
• Leptin circulating levels are directly proportional to body fat mass
• Leptin levels decline with weight loss and increase in appetite.
• Congenital Leptin Deficiency is very rare.
• Leptin and ghrelin have counterbalancing effects on energy balance.
  • Leptin is anorexigenic and reduces weight, while Ghrelin is orexigenic and gains weight
  • Leptin has long-term effects while Ghrelin has acute effects
  • Leptin comes from Adipocytes while Ghrelin comes from the stomach
• Arcuate Nucleus is at the base of the hypothalamus, is near the blood brain barrier, has permeable barrier, and takes in peripheral signals
• Signals taken in are GI and Adipocyte hormones, glucose, fatty acids, and amino acids
• The mesolimbic system (hedonic area) relates to the emotional, pleasurable, and rewarding aspects of eating.
• Hedonic eating is based on reward and pleasure with food.
• Signals are dopamine, opioid, and endocannabinoid pathways.
• food can be craved or enjoyed, even after satiation.
• Dopamine issues leading to overeating may lead to heightened food anticipation, or wanting
• The frontal lobe controls executive functioning and overrides primal behaviors driven by the mesolimbic system.
• Cognitive functioning is best under optimal conditions, and can be adversely affected by steroids, alcohol, or illicit drugs.
• Diminished control of eating behaviors is a possible effect of people with obesity that show disruption of the connection between the frontal lobe and the rest of the brain
• In decreasing fat stores, circulating levels of hormones of leptin and insulin (hormones) levels fall to signal the hypothalamus to inactivate POMC/CART-expressing neurons to promote feeding
• At the same time the inhibitory effect on the AgRP/Neuropeptide Y (NPY)- expressing neurons to increase appetite and decrease energy expenditure lowers.
• As adiposity increases, leptin levels increase, exerting negative feedback to suppress appetite to prevent further weight gain.
• Body fights to regain weight to a "natural weight" by "set points"
• Hormonal adaptation to weight loss will cause weight regain.
• Weight loss produces changes in hormones that encourage weight regain
• "Sustained elevations in appetite-stimulating hormones and decreases in appetite-suppressing hormones"
• Genetically, most obesity cases are polygenic with smaller variations in genes.
• Single gene mutations are rare
• Some cases of obesity are syndromic (Prader-Willi Syndrome)
• This explains why some have dietary behaviours and not all develop obesity in a "health disrupting environment"
• The complications of obesity must be listed and is the 4th learning outcome.
• Medical Complications of obesity include: pulmonary disease (obstructive sleep apnea, hypoventilation syndrome), stroke, idiopathic intracranial hypertension, coronary heart disease, diabetes, dyslipidemia, hypertension, gynecologic abnormalities (abnormal menses, infertility, polycystic ovarian syndrome), pancreatitis, nonalcoholic fatty liver disease (steatosis, steatohepatitis, cirrhosis), gall bladder disease, cancer (breast, uterus, cervix, prostate, kidney, colon, esophagus, pancreas, liver), osteoarthritis, phlebitis, skin, and gout

Principles of Investigation and Management of Complications:

• Obesity-centered history and physical exam
• Metabolic investigations

History

• Should include all elements of routine history (medical, surgical, family, social, allergies, meds)
• Key elements include screening for underlying cause and signs of disease
• Hypothyroidism & Cushing's
• Screen for sleep disorders
• Physical, sexual & psychological abuse
• Discription of eating patterns
• Previous attempts to lose weight
• Screen time, mood, anxiety, substance abuse.
• Internalized weight bias

Exam

• Baseline anthropometric measurements
• Appropriately sized BP cuff
• OSA
• Assess MSK and mobility by Cardio GI exam
• Rule out skin findings
• Endocrine can rule out cause of weight

Investigations for Complications

• No test or diagnostics is accurate.
• Screen or test through suspicion and risk factors
• Measure Metabolic Syndromes
• US measure for non alcoholic fatty liver risk.
• Test underlying cause TSH and URIC
• Consider cushing

Weight loss approaches

• To individual and outcomes like nutrition or reserve.
• Medical nutrition individual patterns for food.
• Calories need short reduction of unsustainable time
• Consider vitD, and micro nutrients risks
• Use Irish clinical guidelines
• Consider foods fruits, nuts, dairy for diet patterns DASH Nordic frequent meal
• Evaluate cardio status for activity

Irish Clinical Guidelines,

• Follow range to the point where you're weight categories align
• Important of the cardiorepiratory fitness.
• Reduced as of some people in the population
• Prevent more lean tissue weight again
• Use behavioral
• Can ask permission for obese patients or refer
• Apply action plan and goal set
• Apply self monitoring behavior

Pharmacotherapy and obesity

• Use if BMI is about 27 or 30
• Recommended with diet or exercise
• Multiple lifestyle modification
• Internal Environment or external environment,

Pharmacotherapy Agent

- Approval is from 1959 to 2023 over various intervals
- Phentermine (short term weight loss only) for Sympathomimetic for 1959
- Orlistat (Xenical) for Lipase inhibitor for 1999
- Phentermine/Topiramat e ER (Qsymia) for Sympathomimetic/GABA receptor modulation/Carbonic Anhydrase inhibition for 2012
- Naltrexone/Bupropion SR (Contrave) for Dopamine/Noradrenaline reuptake inhibitor/Opioid receptor antagonist for 2014
- Liraglutide (Saxenda) for GLP-1 receptor agonist for 2014
- Semaglutide (Wegovy) for GLP-1 receptor agonist for 2021
- Tirzepatide (Mounjaro) for GIP/GLP-1 receptor co-agonist for 2023

• Regain weight is likely after medication

Surgery and therapy

• BMI over 35 and one complication major
• BMI 40 or more
• BMI 30/34 refractory and t2dm
• Different types are gastrectomy or bands

Key Points:

• Obesity is a complex chronic disease characterized by adiposity that impairs health
• BMI is not a standalone tool for individuals
• A lifelong disease requires long term approach
• Focus on best weight
• Patients face stigma
• Hormones are controlled by energy homeostasis
• Genetic is key predisposition factor.
• environment, explains rising levels.
• Holistic approach requires diet psychology and surgery
• Visit RCSI or websites for reference

This quiz covers the complexities of defining obesity, factors influencing its development, and the role of BMI. It also explores the functions of AgRP/NPY and POMC/CART neurons, hedonic eating pathways, and hormonal influences on appetite.