Where are we going today? The Obesity Epidemic What are FFAs & why do we care about them? Gustatory transduction of FFAs Pittman laboratory research:

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1 1 Where are we going today? The Obesity Epidemic What are FFAs & why do we care about them? Gustatory transduction of FFAs Pittman laboratory research: detection of FFAs following CTAs effect of FFAs on other tastes FFA-sensitivity and Obesity NEW INFO!!! Future research direction aka HELP WANTED!

2 Body Mass Index > 25 is overweight > 30 is obese Abdominal Obesity versus 2000: men: 12.7 to 38.3% women: 19.4 to 59.9% BMI Statistics from the CDC ( ) 64% US adults overweight 30% US adults obese (1 in 3) Obesity is the 2 nd leading cause of preventable death in America ( %) 2

3 3 3 major contributors to obesity formation: Genes Level of Physical Activity Over-consumption of highfat & high-caloric food If we know that eating fatty foods causes obesity, why do we continue to overeat high-fat foods? #1 answer = Palatability!

4 Why do we prefer to eat fatty foods? What is the difference between fat-free and regular fat food products Common experience suggests that there is a taste component to fat. Fat has been relegated to a role in texture perception rather than taste. 4

5 5 Enzymes in saliva break down food into dissolved chemicals in the oral cavity Chemicals interact w/ taste receptor cells Neural signal sent to the brain

6 6 Fat is composed of combinations of fatty acids When fat is broken down *enzymes in saliva* these free fatty acids become available for chemical stimulation. What is the free fatty acid composition of corn oil? Palmitic Stearic Oleic Linoleic Linolenic Corn Oil

7 Gilbertson recorded from taste receptor cells while applying free fatty acids. 7 Linoleic Acid DEPOLARIZATION (+) equals neural signal to the brain

8 8 Linoleic acid and other related free fatty acids inhibited the Shaker Kv1.5 channel Linoleic acid enhanced stimulus-induced depolarization of the taste receptor cell Data from: Gilbertson TA, et al. Fatty acid modulation of K+ channels in taste receptor cells: gustatory cues for dietary fat. Am J Physiol Apr;272(4 Pt 1):C

9 A simple paradigm for powerful results! NaCl 9 LiCl

10 10 Measure intake by difference in bottle weight Preference score = LA / (LA + H 2 O) 50% = equal consumption <50% = avoidance of LA compared to H 2 O >50% = preference of LA compared to H 2 O

11 11 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Linoleic Acid Concentration (micromolar) LiCl NaCl

12 12 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Linoleic Acid Concentration (micromolar) LiCl NaCl

13 13 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Linoleic Acid Concentration (micromolar) LiCl NaCl

14 14 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Oleic Acid Concentration (um) * * NaCl LiCl

15 15 100% 90% NaCl LiCl 100% 90% NaCl LiCl 80% 80% Preference Score 70% 60% 50% 40% 30% * * Preference Score 70% 60% 50% 40% 30% * * 20% 20% 10% 10% 0% 0% ETOH Salt ETOH Salt 88 um Linoleic Acid / 88 um Oleic Acid 88 um Oleic Acid / 88 um Linoleic Acid Condition a taste aversion to Linoleic Acid and test with Oleic Acid and vice versa Stimulus Generalization = shared orosensory properties / not lack of discrimination

16 WE GET RESULTS! 16 Physiology & Behavior peerreviewed journal publication 2 student authors: Danielle McCormack Virginia Clyburn Pittman s recent article on fat taste is easily the most comprehensive study of its kind, ever.

17 17 Rats can detect Linoleic & Oleic Acid! The threshold for detection is between 44 & 66 micromolar concentration (14 ul / 1 liter) Small concentration similar to the amount that could be produced by saliva enzymes!

18 18 CT = anterior 2/3 tongue GL = posterior 1/3 tongue GSP = palate Converge in the NST to CNS taste areas

19 2-bottle Preference Tests % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% LiCl & CTX (n=10) NaCl & CTX (n=5) LiCl & ShamCTX (n=5) NaCl & ShamCTX (n=5)

20 2-bottle Preference Tests % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% LiCl & CTX (n=10) NaCl & CTX (n=5) LiCl & ShamCTX (n=5) NaCl & ShamCTX (n=5)

21 Short-Duration (8s) Tests Main Effect Surgery F 1,281 = , p<0.01; Interaction b/w Surgery, Injection, & Concentration F 2,280 = 4.248, p< LA 88 LA 176 LA Concentrations SHAM/LA/NaCl SHAM/LA/LiCl CTX/LA/NaCl CTX/LA/LiCl

22 22 Rats prefer fat (corn oil) similar to humans. Rats detect & avoid very low concentrations of Linoleic and Oleic Acid, free fatty acid components of corn oil. Rats without a chorda tympani nerve can not detect & avoid Linoleic Acid Rats can taste free fatty acids and the signal is likely sent through the chorda tympani nerve!

23 If dietary fat increases intake, do FFAs act in a similar manner on other tastes? 23 The Davis Rig Controlled presentation of up to 16 bottles Computer controls shutter access & counts licks

24 24 Sucrose Sucrose + 88 um Linoleic Sucrose Concentration (mm)

25 25 Sucrose Sucrose + 88 um Linoleic Sucrose Concentration (mm)

26 26 NaCl NaCl + 88 um Linoleic NaCl Concentration (mm)

27 27 NaCl NaCl + 88 um Linoleic NaCl Concentration (mm)

28 28 Citric Acid 1.4 Citric Acid + 88 um Linoleic Citric Acid Concentration (mm)

29 Quinine Alone Quinine + 88 LA Lick Ratio (Tastant / Water) Concentration (mm)

30 Sucrose Alone Sucrose + 88 um OA 120 Mean Licks / 20s Concentration (mm)

31 NaCl Alone NaCl + 88 um OA Lick Ratio (Tastant / Water) Concentration (mm)

32 Citric Acid Alone Citric Acid + 88 um OA Lick Ratio (Tastant / Water) Concentration (mm)

33 Quinine Alone Quinine + 88 um OA Lick Ratio (Tastant / Water) Concentration (mm)

34 34 Both Linoleic & Oleic Acid increased intake of preferable solutions: Sweet / Sucrose Both Linoleic & Oleic Acid decreased intake of unpleasant solutions: Salt / NaCl; Sour / Citric Acid; & Bitter / Q-HCl Supports Gilbertson s theory that FFA inhibition of the K + channels could lead to depolarization of the taste receptor cell and therefore increase the intensity of taste stimuli

35 35 Genes, Taste, & Obesity More Gilbertson research: Two inbred strains of rat show phenotype diffs: Free access to food: one strain overeats (Obese-Prone) & the other maintains normal body weight (Obese-Resistant) Differential nutrient preferences: Obese-prone rats prefer high-fat chow Obese-resistant rats prefer high-carb chow

36 36 Obese-Prone less sensitive to FFAs Theory: Difference in FFA-insensitive channels = smaller feedback signal = regulation & intake O-M = Obese-Prone; S5B = Obese-resistant Data from: Gilbertson TA, et al. (2005) Fatty acid responses in taste cells from obesity-prone and -resistant rats. Physiology & Behavior (86),

37 37 Obese-Prone less sensitive to FFAs Obese-Prone have more K + current, more FFA-insensitive channels (Kv3.1) MASKING! O-M = Obese-Prone; S5B = Obese-resistant Data from: Gilbertson TA, et al. (2005) Fatty acid responses in taste cells from obesity-prone and -resistant rats. Physiology & Behavior (86),

38 38 Dietary fat may act on the taste system through its free fatty acid components. Linoleic & Oleic acid by itself can be detected and avoided by rats following conditioning. Rats treat Linoleic & Oleic acid in a similar manner. The ability to detect and avoid Linoleic Acid is eliminated when the Chorda Tympani nerve is cut. When mixed with other tastes, Linoleic & Oleic acid act to increase the intensity of taste in rats. Differences in FFA-sensitivity may underlie overconsumption of high-fat foods and thus OBESITY!

39 40 AChemS Conference Sarasota April 2003 Danielle McCormack and Petra Herzog Not pictured: Krysta Webster, Sallie Cheek, Steven Robinson, & Dylan Scott

40 41 AChemS Conference Sarasota April 2004 Virginia Clyburn Not pictured: Chelsea Grimsley & Erin Hantske

41 42 AChemS Conference Sarasota April 2005 Lauren Murchison, Sara Shields, Abby Anderson, Hayley O Connor, & Caroline Labban Not pictured: Jennifer Wallace & Leah Harris