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Timothy A. Gilbertson, Ph.D. Biology & The Center for Advanced Nutrition Utah State University OBESITY: the epidemic of obesity the cost of obesity th t f b it the causes of obesity the cure… and the cure and why doesn’t it work ? TASTE BUDS & OBESITY the role of taste ‐ a good system gone awry ? h ff the taste of fat the particular problem of fat how can we control this ? how can we control this ? Obesity Trends* Among U.S. Adults: 1985-2007 ( BMI ≥30, or ~ 30 lbs. overweight for 5’ 5 4” 4 person) (*BMI key No Data <10% 10%–14% Obesity Trends* Among U.S. Adults: 1985-2007 ( BMI ≥30, or ~ 30 lbs. overweight for 5’ 5 4” 4 person) (*BMI key No Data <10% 10%–14% 15%–19% 20%–24% 25% 29% 25%–29% ≥30% 22 y … if Michelangelo were alive today: Why the concern over the rise in obesity? health effects of obesity hypertension h t i diabetes heart disease end stage renal disease joint problems p apnea p sleep cancer metabolic syndrome h i l effects ff t psychosocial >300,000 premature deaths/year "Despite obesity having strong genetic determinants the genetic composition of the determinants, population does not change rapidly. Therefore, the large increase in . . . [obesity] must reflect major changes in non-genetic factors." Hill, James O., and Trowbridge, Frederick L. Childhood obesity: future directions and research priorities. Pediatrics. 1998; Supplement: 571. CAUSES OF OBESITY LIFESTYLE CHOICES eat too much; exercise too little SOCIOECONOMIC FACTORS education level; food cost METABOLIC DISORDERS GENETIC FACTORS obesity linked directly to genes differences in energy expenditure OBESITY: a simple cure food intake (calories in) Energy Balance = energy expenditure (calories out) positive energy balance (weight gain) negative energy balance (weight loss) eat less, exercise more Why don’t we CHOOSE to do this ? if we know this, why aren’t we all thin? food intake E Energy B l Balance = energy expenditure 1950 1990 20xx? 20 ? if we know this, why aren’t we all thin? food intake E Energy B l Balance = energy expenditure …a problem of choice LIFESTYLE CHOICE & OBESITY BMI = weight (kg)/height2 (m) Bray & Popkin Am J Clin Nutr 68:1157, 1998. Carbohydrates: sweet Minerals: salty Protein: amino acid or umami Alkaloids Toxins *Pharmaceuticals *Ph ti l bitter spoiled/rancid food: sour Atropa belladonna deadly nightshade • Carbohydrates: sweet • Minerals: e a s sa salty y • Protein: amino acid or umami • Fat Taste ? Fat: 9 kcal/gm Protein/CHO: 4 kcal/gm …most animals exhibit a preference for dietary fat or …including humans times have changed, our genes have not Thrifty Gene Hypothesis: Natural selection favored the survival of those individuals who could store as many calories as possible, then burn them as slowly as possible [JV Neel, 1962] Can fats activate the taste system? May I h M have my own project? j t? May I have my own project? May I have my own project? Mayy I have myy own p project? j May I have my own project? May I have my own project? Go put fatty acids on a taste cell!!! W. W Todd Monroe Science 244: 1176, 1989 Science 244: 1174, 1989 Todd’s first experiment AJP 272: C1203, 1997 Æ fat has a “taste” since 1997 Æ >1000 articles related to fat & taste …a long way in our understanding of fat taste Dr. Dane Hansen Bhavik Shah Cherry Liu Tian Yu Han Xu Arian Baquero Hala Hadawar gene PATHWAY TO SUCCESS applies to any nutrition-related disorder molecule protein cell tissue/organ b h i behavior treatment me limit carbohydrates (especially processed sugars) Both South Beach and Atkins diets restrict y -- carbs, as diet dilettantes carbohydrates like to say. True, "good carbs" are allowed. But South Beach dieters must say goodbye to potatoes, fruit, bread, cereal, rice, pasta, beets carrots, beets, carrots and corn for the first two weeks. After that, most of these foods remain strongly discouraged. lost weight Æ went off diet Æ sweet taste altered does our taste system reflect our nutritional experience? Dietary Preference in OM & S5B Rats S5B O-M Food Inta F ake (g/da ay) 8 ** S5B/Pl 6 4 ** 2 0 protein carbohydrate fat ** p<0.001 compared w/ O-M Redrawn from Okada et al. Am. J. Physiol 262:R1111, 1992 O-M The Principle of Negative Feedback Negative Feedback & Food Intake activation of pleasure p or reward centers senssory pro operties (taste e) + set point” point “set - + food intake What can we learn from animal models ? S5B O-M identified & characterized fat receptor lean rat – very responsive to fat strong obese rat – not as responsive to fat weak eats less fat w weak sttrong fat intake fat intake eats more fat “does our taste system reflect our nutritional experience?” siblings 60 days 207 gm 368 gm 60 days activation of pleasure or reward centers sensory properties (taste) + “set p point” - + food intake measure fat receptor changes is less responsive to fat (like obesity-prone) obesity prone) ingests more fat “a vicious cycle !?!” put on a diet return to low fat (normal) diet (60 d) parallels with humans… • is this why dieting is so prone to failure? return to low fat (normal) diet (120 d) little/no weight g loss over ate the low fat diet • is our sensory (taste) system working against us? slight recovery of original fat responsiveness Is there hope in the fight against obesity ? education/outreach (to children) Æ exercise; food intake The Surgeon General’s Call to Action to Prevent and Decrease Overweight and Obesity 2001 Is there hope in the fight against obesity ? pharmacological approaches to reduce appetite (“magic bullet”) a develop new targets (we have several) b develop new ways to deliver old drugs Nanomedicine genes pharmaceuticals decrease appetite food intake ‘targeting proteins’ (antibodies, lectins…) Rx nanoparticle enteroendocrine cells loaded with nanoparticles 100 nm Is there hope in the fight against obesity ? nothing can do this! energy balance = food intake energy gy expenditure p Is there hope in the fight against obesity ? from: