Obesity: An expanding epidemic [Slide 23] Gavin Bart, MD Birth of an epidemic [slides1-22 auto-animation 2 second transition] Last 20 years  Spread across country from < 15% in 1985 [slide 1] to > 25% in 2006 [slide 22] Introduction [slide 24] Obesity Major public health issue Has physical, environmental, and genetic influences Is Related to consumption Result from high caloric intake This lecture reviews the following [slide 25] Definition and epidemiology Comorbid illness Mechanism of disease Treatment Obesity Defined [slide 26] Measured through the body mass index (BMI) BMI defined as weight in kilograms / height in meters squared Normal weight - BMI 18.5-24.9 Overweight - BMI 25.0-29.9 Obesity - BMI ≥ 30.0  Class I BMI 30.0-34.9 Class II BMI 35.0-39.9 Class III (extreme) BMI ≥ 40.0 Obesity epidemiology  [slide 27] 66% US population ≥ 20 yrs overweight or obese 32% obese 5% extreme obesity Mexican American 76% overweight or obese Non-Hispanic Black 76% Non-Hispanic White 64% non-Hispanic white women 36% Mexican American women 50% Non-Hispanic black women 65% We now move from [slide 28] Definition and epidemiology to Comorbid illness Obesity morbidity and mortality [slide 29] 300,000 obesity-related deaths in US per year  5x ↑ risk for diabetes  5x ↑ risk for gallbladder disease  Mood disorders (depression and bipolar) 18% in non-obese v. 22% in obese  Obese ↑ hospitalization and death from cardiovascular disease We now move from [slide 30] Comorbid illness to Mechanism of obesity Mechanisms of obesity Environment [slide 31] Types of food available and portion sizes ~3,500 calories = 1 pound weight gain When caloric intake > energy expenditure weight ↑ Increased intake due to increased portion size Sedentary lifestyle Decreased activity (e.g., couch-potato) Decreased mobility (e.g., disability) Genetics comprise 50% of risk for obesity[8;9] [slide 32] Obesity runs in families 75% monozygotic v 60% dizygotic twins Body weight of adoptees relate to biological more than adoptive parents Specific human gene mutations have been identified Leptin Picture child with leptin deficiency Picture after leptin replacement Proopiomelanocortin (POMC) Obesity can be bred in or out of mice Many feedback pathways involved [slide 33] Adipocytes, or fat cells, produce the hormone leptin ↓ feeding by acting in arcuate nuc. of hypothalamus ↑ expenditure by acting in the brain and muscles Stomach produces the hormone ghrelin ↑ feeding by acting in arcuate nuc. and vagus nerve ↓ energy expenditure by acting in brain and adipocytes Both leptin and ghrelin modulate brain activity related to emotion and behavior (e.g., in the hypothalamus/amygdala) Feeding modulates/is modulated by neuropathways ↑ Dopamine when liked food presented and eaten ↑ Endogenous opioids ↑ feeding ↓ in glutamate will initiate feeding ↑ GABA will ↑ feeding ↑ Serotonin ↓ feeding Stress eating and opioids [slide 34] Stress increases sugar intake  Opiates increase sugar intake  Common link: proopiomelanocortin which is precursor for Endogenous opioid beta-endorphin Stress hormone adrenocorticotropin (ACTH) Feeding hormone alpha-melanocyte-stimulating hormone (alpha-MSH) Control of feeding [slide 35] Emotion Stress Boredom Environment Portion size Availability Intrinsic Hormonal regulation Dopamine Dopamine and reward [slide 36]  Pleasurable things increase dopamine Drugs Sex Food Prolonged exposure decreases dopamine Drugs Food BMI and dopamine receptor [slide 37]  Non-obese no relation between D2 and BMI Obese D2 and BMI inverse correlation Dopamine and reward [slide 37] Early exposure Increased dopamine release Increased dopamine receptors (esp. D2) Prolonged exposure Decreased dopamine release Down regulation of receptors Seen with PET imaging in obesity Liking versus craving? [slide 38] Increased motivational activity when hungry  Caused by stress Caused by food deprivation Desire is for sweets What about carbohydrates? [slide 39] They increase  Dopamine Increase opiates Increase serotonin Alcohol is carbohydrate rich  Is both food and drug Increases dopamine, opiates, serotonin Indicates some overlapping pathways The overlap [slide 40] Rats that prefer sugar have increased self-administration Cocaine  Morphine  Alcohol  Drug withdrawal and sweets [slide 41] Increased consumption of sweets after Smoking cessation  Alcohol abstinence  Opiate withdrawal  Cocaine withdrawal  Taste perception is not altered [25;26] What happens during weight loss? [slide 42] Case reports of AUD and other SUD after bariatric surgery Calorie restriction and alcohol Rats ↑ alcohol when calorie restricted Standard drink = 100 calories of alcohol 12 ounces beer 5 ounces wine 1.5 ounces spirits Do dieters seek any kind of calorie? ↑ liquids to overcome surgical reduction of stomach Carbohydrates preferred Ergo ↑ carbohydrate liquids (soda, milkshakes, alcohol?) We now move from [slide 43] Mechanism of disease to Treatment of obesity Weight loss strategies [slide 44] Goals of weight loss Improve health Must address behavioral change Does this mean address neurobiological change? Brain changes persist after weight loss  Brain changes with dieting may predict success  Examples of interventions follow Bariatric surgery (i.e., weight reduction surgery) [slide 45] Goal to ↓ appetite and ↓ absorption Roux-en-Y restricts the size of the stomach and diverts food past much of the duodenum and jejunum Most common bariatric surgery Long-term weight loss 25% body weight Complications: malabsorption, dumping syndrome Vertical banded gastroplasty and laparoscopic adjustable gastric band Restrict size of stomach Long-term weight loss 15% body weight Complications: reflux, stomal stenosis Behavioral  [slide 46] Brief interventions - < 15 minutes advice on: medical aspects of obesity diet change exercise change Diet and exercise combined 5% ↓ in body weight 12-step (Overeaters Anonymous) [slide 47] Change attitudes and behaviors Get peer network Cognitive behavioral therapy [slide 47] Help patient change view of role in eating Help change behaviors to ↑ weight loss Recognize and avoid risky situations Get peer network Weight Watchers, Jenny Craig, etc. combine these Motivational interviewing [slide 48] Emphasize change Discuss patients resistance to change Focus on patient’s perspective Encourage change acceptable to patient Behavioral therapy alone 5% ↓ in body weight Medication [slide 49] Sibutramine (Meridia): inhibits norepinephrine, serotonin, and dopamine reuptake (approved for obesity) Decreases appetite Increases metabolism 5% ↓ in body weight Rimonabant: cannabinoid receptor antagonist (anticipated approval for obesity) Decreases appetite (opposite of marijuana’s effect) Increases metabolism 5% ↓ in body weight Possible depression suicide risk Orlistat (Xenical) (approved for obesity) Reduces fat absorption 5% ↓ in body weight Naltrexone (ReVia)?: opioid receptor antagonist (not approved for obesity) ↓ pleasantness of sucrose to humans No long-term controlled data for efficacy in obesity Potential hepatotoxicity Conclusions [slide 50] Obesity Causes Significant Morbidity and Mortality Overlapping Neuropathways with Addiction Treatment Strategies Surgical Behavioral Self-help Motivational interviewing Cognitive behavioral Pharmacological Future studies needed [slide 51] Behavioral substitution after weight loss? 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