Appetite control, obesity & bariatric surgery

Transcription

1 Appetite contro, obesity & bariatric surgery Care e Roux Experimenta Pathoogy, University Coege Dubin University of Gothenburg Imperia Coege London

2 Dizygotic Twins Monozygotic Twins Borjeson,Acta Paed.1976

3 Response to eptin therapy in a chid with congenita eptin deficiency 5 45 Maes Weight (kg) Chid B 98th centie th centie 2nd centie Age (years)

4 Afferent factors in metaboic reguation Food Intake Energy Expenditure Leptin Insuin Vagus CCK GO Ghrein PYY GLP-1 OXM

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6 Physioogy?

7 Caorie Intake vs PYY dose response 4 * * PYY (pmo/l) * * * * Lean Obese Test mea (kca) 5 ml 9 ml e Roux et a Endocrinoogy 26

8 Arcuate nuceus

9 24-Hr Caoric Intake (kca) 24-Hr Caoric Intake (kca) Effect of PYY3-36 on food intake Obese Lean 4 P=.2 4 P= Saine PYY Saine PYY Batterham et a N Eng J Med 23

10 Change from baseine (mm) Batterham et a. N Eng J Med. 23 Changes in appetite Obese Group 3 Saine 2 1 Peptide YY Infusion Minutes 21

11 Caories (% of saine) PYY3-36 dose response in humans Caorie intake Satiety 15 * * 2 * * * * mm from baseine 15-3 Saine Doses pmo/kg/min *P.5 vs. saine Saine Doses pmo/kg/min * P<.5 e Roux et a. Endocrinoogy. 26

12 PYY causes nausea at high doses e Roux et a Ann Cin Biochem 28

13 GLP-1 effects in humans GLP-1 secreted upon the ingestion of food 5.Brain: Promotes satiety and reduces appetite 4,5 2.α-ce: Suppresses postprandia gucagon secretion ce: Enhances gucosedependent insuin secretion in the pancreas 1 3.Liver: reduces hepatic gucose output 2 4.Stomach: sows the rate of gastric emptying 3 Adapted from 1 Nauck MA, et a. Diabetoogia 1993;36: ; 2 Larsson H, et a. Acta Physio Scand 1997;16: ; 3 Nauck MA, et a. Diabetoogia 1996;39: ; 4 Fint A, et a. J Cin Invest 1998;11:515 52; 5 Zander et a. Lancet 22;359:

14 Mean body weight (kg) Open-abe extension 82-week Exenatide continued to reduce weight Baseine body weight 98 kg 1 kg 1 kg Pacebo BD (N = 128) Exenatide 5 µg BD (N = 128) Exenatide 1 µg BD (N = 137) 1 Pacebo-controed Trias Open-abe extension (a patients exenatide 1 µg BD) Time (week) 82-wk competers; Mean (SE); Weight was a secondary endpoint Adapted from Bonde L, et a. Poster presented at the American Diabetes Association Meeting 25 (Abstract 477P)

15 Mechanisms RYGB 5 for price of 1 1. Reduced gastric size 2. Duodena and gastric remnant excusion 3. Atered bie fow 4. Eary jejuna exposure to food 5. Partia vagotomy

16 Long term weight oss maintenance 42 4 Weight oss Lifestye / Meds +1.6% BMI kg/m Banding -13% Bypass -25% Years of foow-up Sjöström, L. et a. N Eng J Med 24

17 Decreasing adipocyte mass BMI (kg/m 2 ) 5 45 *** 4 *** *** Months post-op Progressive weight oss - Decreased fasting eptin - Decreased fasting insuin Fasting eptin (ng/m) ** *** Months post-op Fasting insuin (pmo/l) ** *** Months post-op

18 Visua anaogue scores VAS - How hungry are you? How hungry VAS - How fu are you? How fu Pre-op 1 month 3 months 6 months Time from end of standard mea (min) Time from end of standard mea (min) e Roux, Borg et a 26 Brit J Surg

19 PYY response after bariatric surgery PYY pmo/l MEAL Lean Obese RYGB Lap Band Time point (min) e Roux et a Ann Surg 26

20 PYY pmo/l/min mm on VAS (funess) PYY immediatey after RYGB PYY Satiety 9 * * * 12 1 * * * * Days Days e Roux, Webourn et a. Ann of Surg 27

21 PYY response pre & post RYGB 75 *** *** *** *** PYY AUC pmo//min Months post-op e Roux et a Ann Surg 29

22 % Weight oss GLP-1 pmo/l/min Good and poor weight oss after RYGB Weight oss GLP-1 5 * 12 * Good Poor Good Poor *P <.5 e Roux et a. Ann Surg. 27.

23 Kca Kca Bocking gut hormones with octreotide Gastric banding Gastric bypass 1 1 * Saine Octreotide Saine Octreotide *P <.5 e Roux et a. Ann Surg. 27

24 Restriction after gastric bypass Norma pressure Low pressure High pressure Björkund, Obers, Fändriks et a Obes Surg 21

25 Physioogica range Dose response curve LEAN OBESE Satiety Bypass/seeve surgery Mea Size

26 Weight oss and food intake Laurenius and Obers et a 21 unpubished

27 Cinic Anecdota Dietary Change preoperative postoperative I Don t Enjoy Burgers Anymore Syndrome Paradoxica as dietary weight oss increases preference for fatty food and sugars Bueter M, e Roux CW & Ashrafian H, unpubished

28 Assessment of food preference High Fat (Favoured) Low Fat (Favoured) Standard High Fat (Contro) Bueter M, e Roux CW & Ashrafian H, submitted

29 Assessment of food preference Bueter M, e Roux CW & Ashrafian H, submitted

30 Taste domains Physioogy post-ingestive effects, e.g. CTA Reward Hedonism ( How much do I ike it? ) Sensory Detection or Discrimination ( What is it? ) Spector A, Neuroscience and Biobehaviora Reviews 24 (2)

31 Activation to High-Caorie Foods after Gastric Bypass R x 6 y 36 OFC ACC Media fronta cortex z -6 Ventra striatum Pre > Post bypass Post bypass > Pre Amygdaa Caudate vacc Ventra striatum y -2 High-caorie food > Objects, n=19, custer threshod Z>2.1, P<.5

32 Breakpoint significanty decreased after gastric bypass. 27 BREAKPOINT LAST COMPLETED RATIO (CLICKS) * PRE POST RYGB PRE POST CONTROLS Miras et a., Spector, and e Roux, In preparation

33 Hypothesis BMI 4 Leptin Insuin 3 2 RYGB / VSG Gut hormones, bie acids energy expenditure, taste Time

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35 Acknowedgements Wecome Trust & NIHR University Coege Dubin Prof Dona O Shea Prof Catherine Godson University of Gothenburg Dr Torsten Obers Prof Lars Fandriks Imperia Coege London Prof Steve Boom Prof Mohammad Ghatei University of Zurich Prof Thomas Lutz Dr Marco Bueter King s Coege London Prof Stephanie Amie Dr Simon Aywin Mr Ameet Pate Miss Cynthia Borg Musgrove Hospita, Taunton Mr Richard Webourn Mr Dimitri Pournaras Mr Aan Osborn Forida State University Prof Aan Spector