Barbara Cannon The Wenner-Gren Institute , Stockholm University

1. Human brown fat is on fire Barbara Cannon The Wenner-Gren Institute, Stockholm University

2. Results in collaboration with(among others) Wenner-Gren Institute Stockholm University Gustavo Abreude Vieira Tore Bengtsson Helena Feldmann Valeria Golozoubova Anders Jacobsson ElainaMaldonado Natasa Petrovic Tomas Waldén and Jan Nedergaard RVC London University of Copenhagen University of Ancona Valentina GburcikNajaZeniusJespersenMarie Cristina Zingaretti James A. TimmonsCamilla ScheeleSaverioCinti Bente Klarlund Pedersen Therese Juhlin

3. A new organ in adult humans: brown adipose tissue

4. Before 2007: ”in man, brownadiposetissue is onlyfound in newborns”

5. An unexpected development from radiology

7. Tensemuscle? Barrington & Maisey 1996

8. ”In all patients, the soft tissueuptake wasclearlylocalisedwithin the fattytissue of the shoulders as demonstrated by PET/CT co-registration.” Hany//von Schulthess 2002 Eur J Nucl Med Mol Imaging

9. 2007:

10. After 2007: ” in man, brownadiposetissue is found in newborns and in (certain?) adults”

11. Classically: keeping human newborns warm

12. Classically: keeping small mammals warm

13. Classically: awakening from hibernation

15. Brown adipose tissue

18. 1

19. 1

20. 1

21. 1

22. 1

23. UCP1 is essential for norepinephrine-induced thermogenesis in brown adipocytes 1

24. UCP1 is the sole mediator of classical nonshivering thermogenesis 1 Enerbäck//Kozak 1997

25. Wild-type mice UCP1(-/-) mice

26. UCP1 is the sole mediator of classical nonshivering thermogenesis 1 Enerbäck//Kozak 1997

27. Wild-type mice UCP1(-/-) mice

28. Wild-type mice UCP1(-/-) mice

29. Wild-type mice UCP1(-/-) mice No cold-induced nonshivering thermogenesis without UCP1

30. How with humans? Do we have classical nonshivering thermogenesis www.med.harvard.edu/ JPNM/chetan/normals

31. UCP1 presence confirmed

32. Two independent – but congruent – studies: Yoneshiro//Saito 2011

33. Two independent – but congruent – studies: Yoneshiro//Saito 2011

34. Two independent – but congruent – studies: Yoneshiro//Saito 2011 200-400 kcal/day 10-20 % increase Muzik//Granneman 2012 BAT+ BAT-

35. We clearly possess nonshivering thermogenesis! Yoneshiro//Saito 2011 200-400 kcal/day 10-20 % increase Muzik//Granneman 2012 BAT+ BAT-

36. We clearly possess nonshivering thermogenesis! Can we adapt to cold?

37. Human brown fat can be recruited, just as in mice. Induced by cold (?) exposure. Saito//Tsujisaki 2009

38. 1

39. 1 burning away food

40. ”work” Food Heat

41. we can abstain - but what if we eat?

42. ”work” Food Heat ”work” Food Heat fat

43. ”work” Food Heat ”special mechanism for extra energy dissipation” ”work” Food Heat fat

44. ”work” Food Heat ”special mechanism for extra energy dissipation” ”work” Food Heat fat ”work” Food Heat fat

45. ”special mechanism for extra energy dissipation” ”work” Food Heat fat brown fat ”work” Food Heat fat • - such a special mechanism exists • (diet-induced thermogenesis) • and that it is entirely located to brown adipose tissue

46. What are the consequences of lack of brown fat thermogenesis?

47. 1

48. ”work” brown fat with UCP1 Food Heat fat

49. ”work” brown fat without UCP1 Food Heat fat Thus, animals/humans without UCP1 should become obese

50. WT WT