Leptin Mechanism

1. ADIPOSE TISSUE AS AN
ENDOCRINE ORGAN
SPECIAL FOCUS ON LEPTIN

2. SESSION OUTCOMES
At the end of the session, the participants should be able to:
1. describe the general structure of an adipose tissue,
2. identify the secretory products found in adipose tissue
and;
3. explain the physiological mechanism of the leptin in
central and peripheral level.

5. N D Y L I
E C Q K O
K I D EN Y

6. N B Y L O
E C P E K
B O N E

7. N B Y P A
R G H E U
H U N EG R

8. N B Y L A
E C T E A
B A L NA C E

9. M O S L I
E H T B Y
O B E IS T Y

10. T K Y R P
E U S B O
P U B RE T Y

11. E I Y I M
M C N U T
M M U IN T YI

12. T I M L B
A S M E O
E T A OB L IM S M

15. A
D
I
P
O
S
E
T
I
S
S
U
E

16. ADIPOSE TISSUE
BROWN
ADIPOSE
TISSUE
WHITE
ADIPOSE
TISSUE

17. WHITE ADIPOSE TISSUE
WAT is comprised of 2 Fractions:
1) adipocytes
2) SVF which consists of:
• preadipocytes
• endothelial cells
• macrophages
WAT is central to energy storage in
the body and the mobilization of this
energy store is highly regulated.

18. Preadipocyte Mature adipocyte
http://www.hsph.harvard.edu/GSHLAB/adipos.html
BASIC ADIPOSE TISSUE EXPANSION

19. J. Magn. Reson. Imaging Vol.21, 4 Pages: 455-462
GENDER DIFFERENCES IN ADIPOSE TISSUE
DISTRIBUTION
Female Male
Original Image
SCAT
Subcutaneous Adipose
Tissue
HIGHLIGHTED WHITE
VAT
Visceral Adipose
Tissue
HIGHLIGHTED WHITE

20. WAT
CUSHIONING
EFFECT
METABOLIC
STORAGE
DEPOT
ENDOCRINE
ORGAN

21. SECRETORY PRODUCTS OF ADIPOSE
TISSUE
Adipose
Tissue
IGF-1
IGFBP
TNF-α
Interleukins
TGF β
FGF
EGF
Fatty Acids
Lactate
Adenosine
Prostaglandins
Glutamine
Unknown Factors
PAI-1
Angiotensinogen
Ang II
Estrogen
Adiponectin
Resistin
Bone
Morphogenic
Protein
Adapted from: Roth, J, et al, Obesity Research, Vol 12, supplement Nov 2004:88S-101S
Leptin

22. WHAT IS LEPTIN?

23. LEPTIN
Leptin (Greek – leptos) means thin
It is a 16 kDa protein hormone that plays a key role
in regulating energy intake and energy expenditure
It is one of the most important adipose derived
hormones
The Ob (Lep) gene (Ob for obese, Lep for leptin) is
located on chromosome 7 in humans

24. Leptin interacts with six types of receptors :
Ob-Ra to Ob-Rf
encoded by a single gene, LEPR
Ob-Ra and Rc → transport leptin across BBB
Ob-Rb → Hypothalamus , regulates energy homeostasis
and neuroendocrine function
Ob-Re → binds circulating leptin
LEPTIN RECEPTOR

25. HOW LEPTIN WORKS?

26. SIGNALLING PATHWAY
Janus Kinase-Signal
Transducer and Activator of
Transcription-3 (JAK-
STAT3),
Activation of neurons
anorexigenic Neuropeptide
POMC/ orexigenic
Neuropeptide Y

27. INCREASE FOOD INTAKE (OREXIGENIC)
• Orexin (lateral hypothalamus)
• Neuropeptide Y (arcuate and paraventricular
nucleus)
• Agouti-Related Protein (arcuate and
paraventricular nucleus)
• Melanin-concentrating hormone(lateral
hypothalamus)

28. DECREASE FOOD INTAKE
(ANOREXIGENIC)
• alpha-Melanocyte-stimulating hormone(MSH) (arcuate
and PVN)
• Cocaine and amphetamine-releasing transcript(CART)
(arcuate and paraventricular nucleus)
• Corticotropin-releasing hormoneCRH) (paraventricular
nucleus)

30. Increase LEPTIN level
Activation of
POMC/CART neurons
Increase α-Melanocyte-
stimulating hormone
Activation of
Melanocortin receptor 4
Food intake
Energy expenditure

31. INDICATOR OF
ENERGY BALANCE

32. SIMPLIFIED MODEL???

33. PARADOX OF LEPTIN AND OBESITY

35. LEPTIN AND PUBERTY

36. LEPTIN AND PUBERTY Leptin binds to ARC KISS
Increase KISSPEPTIN level
Activates GnRH
Stimulates reproductive
cells
LH, FSH,
TESTOSTERONE
GATEKEEPER OF
MAMMALIAN
PUBERTY

38. LEPTIN AND BONE HOMEOSTASIS

39. LEPTIN AND BONE HOMEOSTASIS

40. LEPTIN AND BONE HOMEOSTASIS

41. LEPTIN AND IMMUNE CELLS
Enhance phagocytic
activity in
macrophages
promote production
of pro-inflammatory
cytokines
stimulate chemotaxis
in
polymorphonuclear
cells
promotes lymphocyte
survival
LEPTIN

42. LEPTIN AND VASCULATURE

43. ADIPOSE
TISSUE
PERIPHERAL
EFFECT
REPRODUCTIVE
SYSTEM
BONE
HOMEOSTASIS
IMMUNE
SYSTEM
CENTRAL
EFFECT
ENERGY
HOMEOSTASIS
IN A NUTSHELL

44. Heather C Denroche, Frank K Huynh and Timothy J Kieffer The role
of leptin in glucose homeostasis Journal of Diabetes Investigation
,Volume 3, Issue 2, pages 115–129, April 2012
Christos S. Montozoros , Faiden Magkos,Tina A Dardino , Sang
Yong Leptin in human physiology and pathophysiology Am J Physiol
Endocrinol Meta Oct2011;301(4):E 567-584
Jeffrey M Friedman Function of leptin in nutrition , weight and
physiology Nutrition Review , Vol 60,no-10 oct 2002(11)S1-14
REFERENCES