Obesity: An expanding epidemic [Slide 23]

Gavin Bart, MD


I.                    Birth of an epidemic [slides1-22 auto-animation 2 second transition]

A.     Last 20 years [1]

B.     Spread across country

                                                            1.      from < 15% in 1985 [slide 1]

                                                            2.      to > 25% in 2006 [slide 22]

II.                 Introduction [slide 24]

A.     Obesity

                                                            1.      Major public health issue

                                                            2.      Has physical, environmental, and genetic influences

B.     Is

                                                            1.      Related to consumption

                                                            2.      Result from high caloric intake

C.     This lecture reviews the following [slide 25]

                                                            1.      Definition and epidemiology

                                                            2.      Comorbid illness

                                                            3.      Mechanism of disease

                                                            4.      Treatment


III.               Obesity

A.     Defined [slide 26]

                                                            1.      Measured through the body mass index (BMI)

                                                            2.       BMI defined as weight in kilograms / height in meters squared

                                                            3.      Normal weight - BMI 18.5-24.9

                                                            4.      Overweight - BMI 25.0-29.9

                                                            5.      Obesity - BMI ≥ 30.0 [2]

a.       Class I BMI 30.0-34.9

b.      Class II BMI 35.0-39.9

c.       Class III (extreme) BMI ≥ 40.0

B.     Obesity epidemiology [3] [slide 27]

                                                            1.      66% US population ≥ 20 yrs overweight or obese

a.       32% obese

b.      5% extreme obesity

                                                            2.      Mexican American 76% overweight or obese

                                                            3.      Non-Hispanic Black 76%

                                                            4.      Non-Hispanic White 64%

                                                            5.      non-Hispanic white women 36%

                                                            6.      Mexican American women 50%

                                                            7.      Non-Hispanic black women 65%

C.     We now move from [slide 28]

                                                            1.      Definition and epidemiology to

                                                            2.      Comorbid illness

D.     Obesity morbidity and mortality [slide 29]

                                                            1.      300,000 obesity-related deaths in US per year [4]

                                                            2.      5x ↑ risk for diabetes [5]

                                                            3.      5x ↑ risk for gallbladder disease [5]

                                                            4.      Mood disorders (depression and bipolar) 18% in non-obese v. 22% in obese [6]

                                                            5.      Obese ↑ hospitalization and death from cardiovascular disease[7]

E.      We now move from [slide 30]

                                                            1.      Comorbid illness to

                                                            2.      Mechanism of obesity

F.      Mechanisms of obesity

                                                            1.      Environment [slide 31]

a.       Types of food available and portion sizes

i.         ~3,500 calories = 1 pound weight gain

ii.       When caloric intake > energy expenditure weight ↑

iii.      Increased intake due to increased portion size

b.      Sedentary lifestyle

i.         Decreased activity (e.g., couch-potato)

ii.       Decreased mobility (e.g., disability)

                                                            2.      Genetics comprise 50% of risk for obesity[8;9] [slide 32]

a.       Obesity runs in families

i.         75% monozygotic v  60% dizygotic twins

ii.       Body weight of adoptees relate to biological more than adoptive parents

b.      Specific human gene mutations have been identified

i.         Leptin

                                                                                                                                       i.      Picture child with leptin deficiency

                                                                                                                                     ii.      Picture after leptin replacement

ii.       Proopiomelanocortin (POMC)

c.       Obesity can be  bred in or out of mice

                                                            3.      Many feedback pathways involved [slide 33]

a.       Adipocytes, or fat cells, produce the hormone leptin

i.         ↓ feeding by acting in arcuate nuc. of hypothalamus

ii.       ↑ expenditure by acting in the brain and muscles

b.      Stomach produces the hormone ghrelin

i.         ↑ feeding by acting in arcuate nuc. and vagus nerve

ii.       ↓ energy expenditure by acting in brain and adipocytes

c.       Both leptin and ghrelin modulate brain activity related to emotion and behavior (e.g., in the hypothalamus/amygdala)

d.      Feeding modulates/is modulated by neuropathways[10]

i.         ↑ Dopamine when liked food presented and eaten

ii.       ↑ Endogenous opioids ↑ feeding

iii.      ↓ in glutamate will initiate feeding

iv.     ↑ GABA will ↑ feeding

v.       ↑ Serotonin ↓ feeding

G.     Stress eating and opioids [slide 34]

                                                            1.      Stress increases sugar intake [11]

                                                            2.      Opiates increase sugar intake [12]

                                                            3.      Common link: proopiomelanocortin which is precursor for

a.       Endogenous opioid beta-endorphin

b.      Stress hormone adrenocorticotropin (ACTH)

c.       Feeding hormone alpha-melanocyte-stimulating hormone (alpha-MSH)

H.     Control of feeding [slide 35]

                                                            1.      Emotion

a.       Stress

b.      Boredom

                                                            2.      Environment

a.       Portion size

b.      Availability

                                                            3.      Intrinsic

a.       Hormonal regulation

b.      Dopamine

I.        Dopamine and reward [slide 36] [13]

                                                            1.      Pleasurable things increase dopamine

a.       Drugs

b.      Sex

c.       Food

                                                            2.      Prolonged exposure decreases dopamine

a.       Drugs

b.      Food

J.       BMI and dopamine receptor [slide 37] [14]

                                                            1.      Non-obese no relation between D2 and BMI

                                                            2.      Obese D2 and BMI inverse correlation

K.    Dopamine and reward [slide 37]

                                                            1.      Early exposure

a.       Increased dopamine release

b.      Increased dopamine receptors (esp. D2)

                                                            2.      Prolonged exposure

a.       Decreased dopamine release

b.      Down regulation of receptors

c.       Seen with PET imaging in obesity

L.      Liking versus craving? [slide 38]

                                                            1.      Increased motivational activity when hungry [15]

a.       Caused by stress

b.      Caused by food deprivation

                                                            2.      Desire is for sweets

M.   What about carbohydrates? [slide 39]

                                                            1.      They increase [16]

a.       Dopamine

b.      Increase opiates

c.       Increase serotonin

                                                            2.      Alcohol is carbohydrate rich [17]

a.       Is both food and drug

b.      Increases dopamine, opiates, serotonin

                                                            3.      Indicates some overlapping pathways

N.    The overlap [slide 40]

                                                            1.      Rats that prefer sugar have increased self-administration

a.       Cocaine [18]

b.      Morphine [19]

c.       Alcohol [20]

O.    Drug withdrawal and sweets [slide 41]

                                                            1.      Increased consumption of sweets after

a.       Smoking cessation [21]

b.      Alcohol abstinence [22]

c.       Opiate withdrawal [23]

d.      Cocaine withdrawal [24]

                                                            2.      Taste perception is not altered [25;26]

P.      What happens during weight loss? [slide 42]

                                                            1.      Case reports of AUD and other SUD after bariatric surgery

                                                            2.      Calorie restriction and alcohol

                                                            3.      Rats ↑ alcohol when calorie restricted

                                                            4.      Standard drink = 100 calories of alcohol

a.       12 ounces beer

b.      5 ounces wine

c.       1.5 ounces spirits

                                                            5.      Do dieters seek any kind of calorie?

a.       ↑ liquids to overcome surgical reduction of stomach

b.      Carbohydrates preferred

                                                            6.      Ergo ↑ carbohydrate liquids (soda, milkshakes, alcohol?)

Q.    We now move from [slide 43]

                                                            1.      Mechanism of disease to

                                                            2.      Treatment of obesity


IV.              Weight loss strategies [slide 44]

A.     Goals of weight loss

                                                            1.      Improve health

                                                            2.      Must address behavioral change

                                                            3.      Does this mean address neurobiological change?

a.       Brain changes persist after weight loss [27]

b.      Brain changes with dieting may predict success [28]

                                                            4.      Examples of interventions follow

B.     Bariatric surgery (i.e., weight reduction surgery)[29] [slide 45]

                                                            1.      Goal to ↓ appetite and ↓ absorption

                                                            2.      Roux-en-Y restricts the size of the stomach and diverts food past much of the duodenum and jejunum

a.       Most common bariatric surgery

b.      Long-term weight loss 25% body weight

c.       Complications: malabsorption, dumping syndrome

                                                            3.      Vertical banded gastroplasty and laparoscopic adjustable gastric band

a.       Restrict size of stomach                                                

b.      Long-term weight loss 15% body weight

c.       Complications: reflux, stomal stenosis

C.     Behavioral [30] [slide 46]

                                                            1.      Brief interventions - < 15 minutes advice on:

a.       medical aspects of obesity

b.      diet change

c.       exercise change

                                                            2.      Diet and exercise combined 5% ↓ in body weight

                                                            3.      12-step (Overeaters Anonymous) [slide 47]

a.       Change attitudes and behaviors

b.      Get peer network

                                                            4.      Cognitive behavioral therapy [slide 47]

a.       Help patient change view of role in eating

b.      Help change behaviors to ↑ weight loss

i.         Recognize and avoid risky situations

ii.        Get peer network

                                                            5.      Weight Watchers, Jenny Craig, etc. combine these

                                                            6.      Motivational interviewing [slide 48]

a.       Emphasize change

b.      Discuss patients resistance to change

c.       Focus on patient’s perspective

d.      Encourage change acceptable to patient

                                                            7.      Behavioral therapy alone 5% ↓ in body weight


D.     Medication [slide 49]

                                                            1.      Sibutramine (Meridia): inhibits norepinephrine, serotonin, and dopamine reuptake (approved for obesity)[31]

a.       Decreases appetite

b.      Increases metabolism

c.       5% ↓ in body weight

                                                            2.      Rimonabant: cannabinoid receptor antagonist (anticipated approval for obesity)[32]

a.       Decreases appetite (opposite of marijuana’s effect)

b.      Increases metabolism

c.       5% ↓ in body weight

d.      Possible depression suicide risk

                                                            3.      Orlistat (Xenical) (approved for obesity)[31]

a.       Reduces fat absorption

b.      5% ↓ in body weight

                                                            4.      Naltrexone (ReVia)?: opioid receptor antagonist (not approved for obesity)[33]

a.       ↓ pleasantness of sucrose to humans

b.      No long-term controlled data for efficacy in obesity

c.       Potential hepatotoxicity

V.                 Conclusions [slide 50]

A.     Obesity Causes Significant Morbidity and Mortality

B.     Overlapping  Neuropathways with Addiction

C.     Treatment Strategies

                                                            1.      Surgical

                                                            2.      Behavioral

a.       Self-help

b.      Motivational interviewing

c.       Cognitive behavioral

                                                            3.      Pharmacological

D.     Future studies needed [slide 51]

                                                            1.      Behavioral substitution after weight loss?

                                                            2.      Elucidate common neuropathways

a.       Obesity

b.      Addiction

                                                            3.      Elucidate common genetics

a.       Obesity

b.      Addiction

E.      Until then you should [slide 52]

                                                            1.      Screen for overweight/obesity (measure BMI)

                                                            2.      Screen for AUD (many screens available)

                                                            3.      Advise patients with obesity about impact on health

                                                            4.      Treat or refer for treatment

a.       Behavioral

b.      Pharmacological

c.       Surgical


Reference List


      1.   Centers for Disease Control and Prevention (CDC). Behavioral Risk Factor Surveillance System Survey Data.  2006. Atlanta, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.

      2.   Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. 98-4083. 1998.  NIH Publications.

      3.   C.L. Ogden, M.D. Carroll, L.R. Curtin, M.A. McDowell, C.J. Tabak, and K.M. Flegal, Prevalence of overweight and obesity in the United States, 1999-2004, JAMA 295 (2006) 1549-1555.

      4.   D.B. Allison, K.R. Fontaine, J.E. Manson, J. Stevens, and T.B. VanItallie, Annual deaths attributable to obesity in the United States, JAMA 282 (1999) 1530-1538.

      5.   A. Must, J. Spadano, E.H. Coakley, A.E. Field, G. Colditz, and W.H. Dietz, The disease burden associated with overweight and obesity, JAMA 282 (1999) 1523-1529.

      6.   G.E. Simon, K.M. Von, K. Saunders, D.L. Miglioretti, P.K. Crane, B.G. van, and R.C. Kessler, Association between obesity and psychiatric disorders in the US adult population, Arch Gen Psychiatry 63 (2006) 824-830.

      7.   L.L. Yan, K. Liu, M.L. Daviglus, L.A. Colangelo, C.I. Kiefe, S. Sidney, K.A. Matthews, and P. Greenland, Education, 15-year risk factor progression, and coronary artery calcium in young adulthood and early middle age: the Coronary Artery Risk Development in Young Adults study, JAMA 295 (2006) 1793-1800.

      8.   I.S. Farooqi and S. O'Rahilly, Genetics of Obesity in Humans, Endocr Rev (2006) er.2006-0040.

      9.   G.S. Barsh, I.S. Farooqi, and S. O'Rahilly, Genetics of body-weight regulation, Nature 404 (2000) 644-651.

    10.   A.E. Kelley, B.A. Baldo, W.E. Pratt, and M.J. Will, Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward, Physiol Behav. 86 (2005) 773-795.

    11.   N. Pecoraro, F. Reyes, F. Gomez, A. Bhargava, and M.F. Dallman, Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress, Endocrinology. 145 (2004) 3754-3762.

    12.   A.S. Levine and C.J. Billington, Opioids as agents of reward-related feeding: a consideration of the evidence, Physiol Behav. 82 (2004) 57-61.

    13.   G.J. Wang, N.D. Volkow, P.K. Thanos, and J.S. Fowler, Similarity between obesity and drug addiction as assessed by neurofunctional imaging: a concept review, J Addict. Dis. 23 (2004) 39-53.

    14.   G.J. Wang, N.D. Volkow, J. Logan, N.R. Pappas, C.T. Wong, W. Zhu, N. Netusil, and J.S. Fowler, Brain dopamine and obesity, Lancet. 357 (2001) 354-357.

    15.   D.M. Small, Toward an understanding of the brain substrates of reward in humans, Neuron. 33 (2002) 668-671.

    16.   R. Spangler, K.M. Wittkowski, N.L. Goddard, N.M. Avena, B.G. Hoebel, and S.F. Leibowitz, Opiate-like effects of sugar on gene expression in reward areas of the rat brain, Brain Res. Mol. Brain Res. 19 (2004) 134-142.

    17.   A.B. Kampov-Polevoy, J.C. Garbutt, and D.S. Janowsky, Association between preference for sweets and excessive alcohol intake: a review of animal and human studies, Alcohol Alcohol. 34 (1999) 386-395.

    18.   B.A. Gosnell, Sucrose intake predicts rate of acquisition of cocaine self-administration, Psychopharmacology (Berl). 149 (2000) 286-292.

    19.   B.A. Gosnell, K.E. Lane, S.M. Bell, and D.D. Krahn, Intravenous morphine self-administration by rats with low versus high saccharin preferences, Psychopharmacology (Berl). 117 (1995) 248-252.

    20.   S.M. Bell, B.A. Gosnell, D.D. Krahn, and R.A. Meisch, Ethanol reinforcement and its relationship to saccharin preference in Wistar rats, Alcohol. 11 (1994) 141-145.

    21.   J. Rodin, Weight change following smoking cessation: the role of food intake and exercise, Addict. Behav. 12 (1987) 303-317.

    22.   D. Krahn, J. Grossman, H. Henk, M. Mussey, R. Crosby, and B. Gosnell, Sweet intake, sweet-liking, urges to eat, and weight change: relationship to alcohol dependence and abstinence, Addict. Behav. 31 (2006) 622-631.

    23.   A. Morabia, J. Fabre, E. Chee, S. Zeger, E. Orsat, and A. Robert, Diet and opiate addiction: a quantitative assessment of the diet of non-institutionalized opiate addicts, Br J Addict. 84 (1989) 173-180.

    24.   Smith D, Ho A, Cambor R, and Kreek MJ. Changes in physiological parameters of recently abstinent hospitalized cocaine addicts. The Problems of Drug Dependence, 1997: Proceedings from the 59th Annual Meeting of The College on Problems of Drug Dependence [178]. 21997. NIDA Research Monograph NIH Pub. 98-4305.

    25.   A. Bogucka-Bonikowska, H. Baran-Furga, K. Chmielewska, B. Habrat, A. Scinska, A. Kukwa, E. Koros, W. Kostowski, E. Polanowska, and P. Bienkowski, Taste function in methadone-maintained opioid-dependent men, Drug Alcohol Depend. 68 (2002) 113-117.

    26.   A. Bogucka-Bonikowska, A. Scinska, E. Koros, E. Polanowska, B. Habrat, B. Woronowicz, A. Kukwa, W. Kostowski, and P. Bienkowski, Taste responses in alcohol-dependent men, Alcohol Alcohol. 36 (2001) 516-519.

    27.   A. DelParigi, K. Chen, A.D. Salbe, J.O. Hill, R.R. Wing, E.M. Reiman, and P.A. Tataranni, Persistence of abnormal neural responses to a meal in postobese individuals, Int. J Obes. Relat Metab Disord. 28 (2004) 370-377.

    28.   A. DelParigi, K. Chen, A.D. Salbe, J.O. Hill, R.R. Wing, E.M. Reiman, and P.A. Tataranni, Successful dieters have increased neural activity in cortical areas involved in the control of behavior, Int. J Obes. (Lond). 31 (2007) 440-448.

    29.   J. Colquitt, A. Clegg, E. Loveman, P. Royle, and M.K. Sidhu, Surgery for morbid obesity, Colquitt. J, Clegg. A, Loveman. E. , Royle. P. , Sidhu. MK. Surgery for. morbid. obesity. Cochrane. Database. of Systematic. Reviews. : Reviews. 2005. Issue. 4 John. Wiley. & Sons. , Ltd. Chichester, UK.

    30.   K. Shaw, P. O'Rourke, M.C. Del, and J. Kenardy, Psychological interventions for overweight or obesity, Shaw. K. , O'Rourke. P. , Del. Mar. C. , Kenardy. J. Psychological. interventions. for. overweight. or. obesity. Cochrane. Database. of Systematic. Reviews. : Reviews. 2005. Issue. 2 John. Wiley. & Sons. , Ltd. Chichester, UK.

    31.   R. Padwal, S.K. Li, and D.C.W. Lau, Long-term pharmacotherapy for obesity and overweight, Padwal. R. , Li SK. , Lau. DCW. Long. term. pharmacotherapy for. obesity. and overweight. Cochrane. Database. of Systematic. Reviews. : Reviews. 2003. Issue. 4 John. Wiley. & Sons. , Ltd. Chichester, UK.

    32.   C. Curioni and C. André, Rimonabant for overweight or obesity, Curioni. C. , André. C. Rimonabant. for. overweight. or. obesity. Cochrane. Database. of Systematic. Reviews. : Reviews. 2006. Issue. 4 John. Wiley. & Sons. , Ltd. Chichester, UK.

    33.   J.E. Mitchell, J.E. Morley, A.S. Levine, D. Hatsukami, M. Gannon, and D. Pfohl, High-dose naltrexone therapy and dietary counseling for obesity, Biol. Psychiatry. 22 (1987) 35-42.