Why Obesity Is A Chronic Disease Arya M Sharma, MD, FRCP(C) Professor of Medicine Chair in Obesity Research & Management University of Alberta Edmonton, AB, Canada www.drsharma.ca
Global Obesity Map 2014 The Lancet, 2016
Societal influences Individual psychology Food Production Food Consumption Individual activity Activity environment Biology
Prevalence of Obesity in Canada Twells LK, et al. CMAJ Open 2014
Overview/Objectives Describe the chronic nature of obesity Understand mechanisms of weight homeostasis Apply principles of chronic disease management
Recovery of Lost Weight After Diet-Induced Weight Loss (16 studies) 100 % weight regain 80 60 40 20 0 0 1 2 3 4 5 Duration of Follow-Up Safer, So. Med. J. 84:1470, 1991
Successful Weight-Loss Maintainers National Weight Control Registry http://www.obesity.org/prevention/maintaining.shtml Limit their intake of certain foods Consume an average of 1400 Cal/day 24% of cal from fat 19% of cal from protein 56% of cal from carbohydrates. Eat five times a day Burn an average of 2,800 Cal a week through exercise 400 Cal/day or 60 min of walking at 15 min/mile
Isn t Obesity Simple? Genetics Diet Energy In +/- +/- Exercise Energy Out Energy Regulation is Complex! Sharma AM 2007
Central Control of Energy Metabolism
Long-Acting Adiposity Signals and Short- Acting Meal-Related Signals that Contribute to Energy Balance Marx J: Science 2003;299:846
Adipose Tissue Adipokines Sharma AM & Staels B, JCEM 2007
Adaptations To Weight Loss Hormonal changes (e.g. decrease in leptin, increase in ghrelin, etc.) Increase in appetite Decrease in metabolic rate Decrease in activity thermogenesis
Biggest Losers Fight a Slower Metabolism New York Times 2016
Persistence of Hunger and Desire to Eat After Weight Loss Sumithran P, et al. NEJM 27;365:1597-604
Persistence Ghrelin, Peptide YY, Amylin, and Cholecystokinin (CCK) After Weight Loss Sumithran P, et al. NEJM 27;365:1597-604
Astrogliosis
Morphological Microglial Reactivity in Diet-Induced Obesity in Mice (AIF-1-ir) Stefanie Kälin et al., Nature Reviews Endocrinology 2015 Chow-fed High-fat diet
Horvath TL, et al. PNAS 2010;107:14875
Diet-Induced Hypothalamic Reactive Gliosis and Obesity in Obesity-Prone Rats Horvath TL, et al. PNAS 2010;107:14875
These data suggest that consumption of an HFD has a major impact on the cytoarchitecture of the arcuate nucleus in vulnerable subjects, with changes that might be irreversible due to reactive gliosis. Horvath TL, et al. PNAS 2010;107:14875
Hypothalamic Innate Immune Reaction in Obesity Stefanie Kälin et al., Nature Reviews Endocrinology 2015
Stunkard: Twin Studies Monozygous Share genes and environment
Stunkard: Twin Studies Monozygous Share genes and environment Heterozygous Share environment
Gene Map of Common Obesity El-Sayed Moustafa et al. Nature Reviews Endocrinology, 2013
Epigenetics nihroadmap.nih.gov
J Clin Endocrinol Metab. 2009;94:4275 49 mothers with bariatric surgery; 54 children before and 57 after surgery 2.5-26 yrs old Children born after surgery: 3-fold lower prevalence of severe obesity (11 vs. 35%) greater insulin sensitivity improved lipid profile lower C-reactive protein
Increased Melanocortin Expression in Fetal Offspring of Nonhuman Primates Fed a High-Fat Diet Grayson BE, et al. Endocrinology 2010;151:1622 Maternal Control Diet Maternal High Fat Diet
Phases of Obesity Treatment Phase I (Weight Loss) Phase II (Weight-Loss Maintenance) Weight When you stop treatment, the disease comes back! 3-6 months Indefinitely www.drsharma.ca
Typical Treatment Success Behaviour Modification (BM) ~ 3-5% Years
Typical Treatment Success Behaviour Modification (BM) ~ 3-5% Years BM+Surgery ~ 20-30%
Typical Treatment Success Behaviour Modification (BM) ~ 3-5% Treatment Gap Years BM+Surgery ~ 20-30%
Typical Treatment Success Behaviour Modification (BM) ~ 3-5% Medication Years BM+Surgery ~ 20-30%
Pharmacological Targets in Obesity Bray et al. Lancet 2016
A Word On Burning Calories! Image: Canadian Obesity Network
Jean-Philippe Chaput & Arya M. Sharma
Non-Caloric Benefits of Regular Exercise Cardiorespiratory fitness Insulin Sensitivity Ectopic Fat Daily Routine Self-Esteem Mood Stress Anxiety ADHD Sleep Energy Improved Weight Management & Better Health! Chaput JP & Sharma AM BJN, 2011
Key Points Once established obesity becomes a chronic, often progressive disease Complex neuro-endocrine factors defend against weight loss and promote weight regain Recognising obesity as a disease can reduce the bias and stigma of obesity improve education of health professionals in obesity foster investments into obesity prevention and research improve access to obesity treatments www.drsharma.ca
www.drsharma.ca