1. Obesity – a 2014 Overview Tim Greenaway PhD, FRACP Director Clinical Endocrinology Royal Hobart Hospital

2. Scope of Talk Definition Prevalence Significance Pathophysiology of weight regulation Treatment – difficult! (recidivism)

3. Obesity Excess body fat Defined anthropometrically by Body Mass Index (BMI) > 30kg/m 2 Prevalence increasing (63.4% Australian adult population overweight or obese – Australian Health Survey 2011-12) Associated with increased morbidity/mortality

4. Venus of Willendorf. c.24,000-22,000 BCE (Naturhistorisches Museum, Vienna)

5. Australian Health Surveys Obesity Data

6. Trends in the Number of Obese Persons, According to Region Ezzati M, Riboli E. N Engl J Med 2013;369:954-964

8. Medical Consequences of Obesity

9. Deaths and Burden of Disease Attributable to Selected Behavioral and Dietary Risk Factors in 2010 and the Metabolic and Physiological Mediators of Their Hazardous Effects Ezzati M, Riboli E. N Engl J Med 2013;369:954-964

10. Hepatic steatosis Insulin resistance  -cell dysfunction Diabetes Atherogenesis Metabolic effects of Visceral WAT accumulation Nat Rev Immunol, 2006

12. The March of Civilisation?

13. The “Lucky” Country

14. Activity is Declining

15. First Law of Thermodynamics The first Law of Thermodynamics, or energy balance, states that in a closed system, energy can neither be created nor destroyed, only transformed or transferred “Calories in = calories out” However, Humans are not closed systems

18. Weight is Regulated by the Brain

20. Arcuate Nucleus NPY CART AGRP aMSH Lateral Hypothalamus Orexin MCH Paraventricular Hypothalamic Nucleus Oxytocin CRH Brain Stem FOOD INTAKE ENERGY EXPENDITURE Cerebral Cortex conscious will Stomach Ghrelin  Fat Leptin Intestine CCK PYY 3-36 GLP-1 Oxyntomodulin  Pancreas Insulin Amylin PP Opioids Dopamine Endocannabinoids Serotonin Noradrenaline - -

21. Obesity is Familial

22. BMI of Subjects 21 22 23 24 25 26 27 Adoptee Weight Class Stunkard AJ, N Engl J Med 1986;314(4):193-8 Genes and the Environment: Danish Twin Adoption StudiesThinIMedianIIOverweightIIIObeseIV IIIIIIIV Biological Parents IIIIIIIV Adoptive ParentsFatherMother

23. Why is weight nearly always regained?

24. Diet and behavioural intervention Very-low-calorie diet Modified diet plus behaviour therapy Very-low-calorie diet plus behaviour therapy Years after intervention 0 -5 -10 -15 -20 5 1 intervention 23 45 Weight change (kg)

25. Ghrelin levels after weight loss Cummings DE et al. N Engl J Med. 346:1623-30 2002

27. Original Article Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet Iris Shai, R.D., Ph.D., Dan Schwarzfuchs, M.D., Yaakov Henkin, M.D., Danit R. Shahar, R.D., Ph.D., Shula Witkow, R.D., M.P.H., Ilana Greenberg, R.D., M.P.H., Rachel Golan, R.D., M.P.H., Drora Fraser, Ph.D., Arkady Bolotin, Ph.D., Hilel Vardi, M.Sc., Osnat Tangi-Rozental, B.A., Rachel Zuk-Ramot, R.N., Benjamin Sarusi, M.Sc., Dov Brickner, M.D., Ziva Schwartz, M.D., Einat Sheiner, M.D., Rachel Marko, M.Sc., Esther Katorza, M.Sc., Joachim Thiery, M.D., Georg Martin Fiedler, M.D., Matthias Blüher, M.D., Michael Stumvoll, M.D., Meir J. Stampfer, M.D., Dr.P.H., for the Dietary Intervention Randomized Controlled Trial (DIRECT) Group N Engl J Med Volume 359(3):229-241 July 17, 2008

28. Weight Changes during 2 Years According to Diet Group Shai I et al. N Engl J Med 2008;359:229-241

30. Physical activity, dietary energy intake, and smoking in Cuba, 1980-2010 ©2013 by British Medical Journal Publishing Group Franco M et al. BMJ 2013;346:bmj.f1515

31. Prevalence of obesity and diabetes, incidence, and mortality in Cuba, 1980-2010 Franco M et al. BMJ 2013;346:bmj.f1515 ©2013 by British Medical Journal Publishing Group

32. Distributions of body mass index as recorded by national surveys conducted in Cienfuegos in 1991, 1995, 2001, and 2010 Franco M et al. BMJ 2013;346:bmj.f1515 ©2013 by British Medical Journal Publishing Group

33. Original Article Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 3-Year Outcomes Philip R. Schauer, M.D., Deepak L. Bhatt, M.D., M.P.H., John P. Kirwan, Ph.D., Kathy Wolski, M.P.H., Stacy A. Brethauer, M.D., Sankar D. Navaneethan, M.D., M.P.H., Ali Aminian, M.D., Claire E. Pothier, M.P.H., Esther S.H. Kim, M.D., M.P.H., Steven E. Nissen, M.D., Sangeeta R. Kashyap, M.D., for the STAMPEDE Investigators N Engl J Med Volume 370(21):2002-2013 May 22, 2014

34. Mean Changes in Measures of Diabetes Control from Baseline to 3 Years Schauer PR et al. N Engl J Med 2014;370:2002-2013

35. Polar Chart of Scores for Quality of Life at Baseline and 3 Years after Randomization Schauer PR et al. N Engl J Med 2014;370:2002-2013

36. Anatomical sites of brown, white and beige adipocytes

37. Phenotypes of Adipose Tissue Depots a.White Adipose Tissue b.Brown Adipose Tissue c.Browning of WAT d.Transmission EM beige adipocytes within WAT depot

38. Adipocyte plasticity: browning of adipose tissue is an adaptive and reversible response to environment

39. Obesity management – What does the future hold? Population health Built environment Food – cost, access Activity Childhood obesity? Individual Multidisciplinary approach Behaviour modification Pharmacological intervention (phentermine/topiramate, lorcaserin, GLP-1 analogues, orlistat) Bariatric surgery