Overweight and Obesity FROM WOMB TO TOMB! DR.LUIS RAUL RUIZ RIVERA F.A.C.E.
Overview • Definition, Prevalence & Consequences of Obesity • Healthy Lifestyles • Assessment of Obesity • Treatments for Obesity WHY BOTHER?? DR. DAVID KATZ [YALE] Today’s kids may become the first generation in the hx of mankind to have a life expectancy projected to be less than their parents!!!!
Definition of Obesity • 0 -2 years: Wt/Ht > 95%ile • 2 – 18 years: BMI > 95%ile • At Risk: BMI 85 – 95%ile • Adult Overweight: BMI > 25 – 30 • Obesity Class 1: BMI 30 – 34.9 (30#) • Obesity Class 2: BMI 35 – 39.9 (50#) • Obesity Class 3: BMI > 40 (100#) • Grossly: 20% above IBW!!!!
Prevalence of Obesity • Childhood and adolescent obesity increased from 5% to 16% in the last 20 years • Adulthood obesity increased from 12% to 21% in 10 years. • 20 million US adults with BMI over 35 • 68 million US obese adults (BMI > 30)
Weight Gain: Energy In 3500 calories = 1 pound • 100 calories extra per day • = 36,500 extra per year • = 10.4 lbs weight gain • Question: How much is 100 calories? • Answer: Not very much! • 1 glass skim milk, or • 1 banana, or • 1 slice cheese, or • 1 tablespoon butter
Factors predispose to obesity • Genetic – familial tendency.40%;Polygenic • Sex – women more susceptible . • Activity – lack of physical activity. • Psychogenic – emotional deprivation, depression . • Social class – poorer classes. • Alcohol – problem drinking. • Smoking – cessation smoking. • Prescribed drugs – tricyclic derivatives,insulin,sulfon, . Alfa and B blockers,etc
Nurture vs Nature • Overeating learned early in childhood OBESITY IS NURTURE LEAVING NATURE TO EXPRESS IT SELF!! • Bottle vs breast • Urging children to eat more, clean their plates • Use of food as a reward;pleasure signals from limbic and dopaminergic systems! Could be accepted as an addiction in certain individulas?
Live to Eat! Eat to Live!
Weight Gain: How Does It Happen? • Energy imbalance • calories consumed not equal to calories used • Over a long period of time • Due to a combination of several factors • Individual behaviors • Social interactions • Environmental factors • Genetics; but when it begins??
Intrauterine: “Thrifty Gene” • More than 250 obesity-associated genes • We all have at least one • Only 2 lean-associated genes • 15 single gene mutations predict obesity • If one parent obese, increase risk 3 fold • If both parents obese, increase risk 13 fold • Gene marker: MC4R causes >5% of obesity • Genes set threshold of receptor response
Intrauterine “Programming” Barker Hypothesis • Alterations in fetal nutrition and endocrine status result in permanent developmental adaptations in structure, physiology, and metabolism thereby predisposing the fetus to cardiovascular, metabolic, and endocrine disease in adult life.
Intrauterine: Nutrigenomics • The science of interaction of nutrition and gene expression in utero • Role of “priming” of metabolic responses that persists into adulthood • Goal of optimal maternal nutrition prior to and during pregnancy
Intrauterine: Options for Intervention • Reduce pre-pregnancy obesity • Address maternal diet and exercise especially in first trimester • Reduce glycemic index of intake to reduce intrauterine insulin and IGF1 levels • Establish new nutrition and weight gain goals for pregnancy
Infancy: Recommendations: • Encourage breast feeding to allow infant to self-regulate intake and increase flavor preference • Delay introduction of solid foods until after 4 – 6 months • Wean from bottle use by 18 months of age • Improve WIC wellness education
Value of Breast feeding • Slower weight gain in first weeks • Self regulated caloric intake • Lower insulin levels in first year • Wider food preferences after 2 years of age, lower sugar, lower salt. • Reduced or delayed development of Type 2 diabetes in Pima Indians
LA FAMOSA ESTATUA REGRESA A ITALIA DESPUÉS DE HABER SIDOEXPUESTA EN LOS ESTADOS UNIDOS DE AMERICA
Con el patrocinio de: BUT HAVE IN MIND Mc D IS THE LARGEST PRIVATE REAL ESTATE OWNER IN THE WORLD AND EMPLOYS THOUDSANDS!
Prevalence of Dieting • 40% of all women • 25% of all men Diet products are a 33billion dollar industry and counting!!.
Sustaining Hunger and Satiety • Protein --- most satiating • Complex carbohydrates --- satiating • Fat --- stimulate and entice people to eat more
Evolving Pathology • More in and less out = weight gain • More out and less in = weight loss • Hypothalamus • control center for hunger and satiety • Endocrine disorder • where are the hormones?
ANOREXIGENIC α MSH (Melanocyte-stimulating hormone) Leptin Serotonine Nor-epinephrine Corticotropin- realeasing hormone Insulin CCK ( Cholecystokinin) GLP (glucagon-like peptide) CART (Cocaine and amphetamine related transcript) Peptide YY OREXIGENIC (HUNGER) Neuropeptide Y (NPY) Agouti-related protein (AgRP) MCH (Melanin-concentrating hormone) Orexins A and B Endorphins Galanin (GAL) Amino acids ( glutamate & GABA) Cortisol Ghrelin Cannabinoids NEUROTRANSMITERS AND HORMONES
NEURAL CENTRES REGULATES FOOD INTAKE • Hypothalamus containsHUNGER and SATIETYcentre • Paraventricular, Dorsomedial, and Arcuate nuclei of the Hypothalamus also play a major role • Chemical cross talk among the neurons of the hypothalamus • Hypothalamus receives signals from different sites
SATIETY REGULATOR • The hypothalamus • When feeding cells are stimulated, they signal us to eat • When satiety cells are stimulated, they signal us to stop eating • Sympathetic nervous system • When activity increases, it signals to stop eating • When activity decreases, it signals to eat
Leptin;from the greek LEPTOS=thin! • Protein hormone secreted by adipocytes • Levels correlate with lipid content of cells • Leptin acts on the hypothalamus to reduce hunger and to stimulate energy expenditure • Coded by the OB gene ( 167 aminoacids)
Energy in=Energyout? Obese children are “leptin resistant” (leptin receptors are blocked) They are stuck in “Conserve Energy” mode Their brains are starving, so they are constantly seeking more food=crying during the night! Yet very little of that energy is available for activity, since it is routed away into the fat cells. These children don’t sleep well=Adult sleep apnea???
What blocks leptin? Brain damage to the leptin receptor area: hypothalamic obesity syndrome Insulin excess blocks leptin receptors (Fructose is what leads to insulin excess) Lustig, Ped Annals, 35:12 Dec 2006
INSULIN excess blocks LEPTIN Insulin receptors in the brain share the same substrate as leptin receptors When there is excess insulin, it hogs all the substrate, leaving none for leptin to use. Leptin attaches to the receptor, but nothing happens.LEPTIN RESISTANCE!!!
FRUCTOSE Fructose is absorbed from the intestine and enters the liver without insulin regulation, AND it does not suppress ghrelin (hunger hormone). It is then converted into acetyl-CoA, which floods the Kreb cycle, forcing excess production of FFA, triglycerides and VLDL lipoproteins.
FRUCTOSE-high fructose corn syrup a mayor cause of HYPERINSULINEMIA! All this excess fat production leads to fatty liver which causes hepatic insulin resistance Fructose also activates the enzyme jnk-1 which causes hepatic inflammation, and more insulin resistance Faulty feedback to the liver results in massive insulin production, leptin resistance, and obesity
Ghrelin (Hunger Hormone) • Hormone secreted in the stomach • Acts on the hypothalamus to stimulate appetite • Levels peak just before meals and drop afterward
Orexin-A (hypocretin-1) Small peptide hormone released by the hypothalamus to act on the rest of the brain,discovered in1998 it’s a VIGILANCE PEPTIDE. It signals hunger, after the hypothalmus is stimulated by ghrelin from the stomach It also signals wakefulness, so that your brain stays awake long enough to seek food, and not to hibernate!Inhibited by leptin and activated by Ghrelin and hypoglycemia Another reason obese children don’t sleep well
ENDOCANNABINOID SYSTEM • Two endocannabinoids 1. Anandamide 2. 2 arachidonyl glycerol • Receptors are CB1 (abundant in the brain) CB2 ( present in immune cells) • Control food intake • Regulate action of other mediators of appetite • CB1 receptors play a key role in energy balance, and are directly implicated in lipid and glucose metabolism.
C C K • Cholecystokinin released from duodenum in response to fat entry • Direct effect on feeding centre to reduce subsequent feeding by activation of the MELANOCORTIN pathway in the hypothalamus FOOD INTAKE MELANOCRTIN SYSTEM + CCK
INSULIN FOOD INTAKE ENERGY EXPENDITURE - + INSULIN, GLP
PEPTIDE YY PYY: 1. made in response to food entering the GIT especially from ILEUM and COLON 2. Binds to an inhIbitory receptor on NPY/AgRP secretion of NPY and AgRP APPETITE FEEDING PYY
TEMPERATURE REGULATION AND FOOD INTAKE The thermostatic hypothesis • Exposure to cold increases feeding • Exposure to heat decreases feeding • Caused by interaction within the hypothalamus between temperature and food intake – regulating system
APPETITE CONTROL AT HYPOTHALAMIC LEVEL: SUMMARY (3) • Leptin and insulin: 1. Stimulate- POMC/CART neurons CART and -MSH levels 2. Inhibit NPY/AgRP neurons NPY and AgRP Net effect : ↑ Satiety and Appetite • Ghrelin stimulates NPY/AgRP NPY and AgRP secretion ↑ appetite • PYY3-36 is a homolog of NPY Binds to an inhibitory receptor on NPY/AgRP secretion of NPY and AgRP Appetite
Bad News for Dieters • Leptin • Dieting decreases leptin levels • Reducing metabolism, stimulating appetite • Ghrelin • Levels in dieters are higher after weight loss • The body steps up ghrelin production in response to weight loss • The higher the weight loss, the higher the ghrelin levels
Assessment • Measure BMI • Measure waist circumference • “Apple shape” body is higher risk for DM, CVD, HTN • Waist larger than 40 inches for men • Waist larger than 35 inches for women
Assessment • Assess for other risk factors • Existing high risk disease: • coronary heart disease; other atherosclerotic diseases; type 2 diabetes; sleep apnea • Diseases associated with obesity • Gynecological problems; osteoarthritis; gallstones; stress incontinence low TESTOSTERONE leading to erectile dysfunction! • Cardiovascular risk factors (3 or more = high risk) • Cigarette smoking; Hypertension; LDL >130; HDL <35; fasting glucose = 110 to 125; family history of premature CHD; men age > 45; women age > 55 • Other risk factors • Physical inactivity; elevated serum triglycerides • Medications associated with obesity • These risk factors increse mortality and worst of all morbidity=INCAPACIDAD!!!!
Treatment Approach • A multi-faceted approach is best • Diet • Physical activity • Behavior change • “A” Recommendation