1. Speaker: Wei-Zhi Hsu Advisor : Jun-Yi Yang 2017/05/02
Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota
Speaker: Wei-Zhi Hsu
Advisor : Jun-Yi Yang
2017/05/02

2. low-grade inflammation
Obesity
Insulin resistance
type 2 diabetes…
Obesity-associated
low-grade inflammation
Composition of the gut microbiota are associated with the development of obesity and its associated metabolic disorders. (Science 341, (2013))
Obesity-induced gut dysbiosis caused by either environmental or genetic factors impairs intestinal integrity.(Gut 58, 1091–1103 (2009))

3. Gut microbiota
The endotoxin lipopolysaccharide (LPS) from intestinal Gram-negative bacteria get into the bloodstream, leading to metabolic inflammation and insulin resistance (Invest. 115, 1111–1119 (2005).)

4. Obesity Pro-inflammation
LPS : Lipopolysaccharide
LBP : Lipobinding protein
Journal of Molecular Endocrinology 51:2 ,R51–R64, 2013

5. Obesity Pro-inflammation, insulin resistance
November 2015 | Volume 6 | Article 341

6. Previous study
Triterpenes and polysaccharides isolated from G. lucidum inhibit adipocyte differentiation and produce hypoglycaemia effects in diabetic mice.
Proteoglycans isolated from G. lucidum fruiting bodies induce antidiabetic, antihyperlipidemic and antioxidant activities.

7. Pro-inflammation cytokines
Aim
How G. lucidum produces any effect on body weight and obesity-related disorders?
Obesity
Insulin resistance
Imflammation
Intestinal integrity
Pro-inflammation cytokines
Gut microbiota
Endotoximia
(LPS)
TLR4
Insulin resistance

8. Pro-inflammation cytokines
Obesity
Insulin resistance
Imflammation
Intestinal integrity
Pro-inflammation cytokines
Gut microbiota
Endotoximia
(LPS)
TLR4

9. Water extract of G. lucidum mycelium (WEGL)
400 g of dried G. lucidum mycelium / 10 L water
agitation at 150 r.p.m. for 30 min at 121 °C
cooled to room temperature (22 °C)
centrifugation at 5,894g for 30 min at 4 °C
The supernatant was concentrated at 65 °C to obtain a final volume of 2 L.

10. WEGL prevents HFD-induced obesity in mice
mice fed for 2 months
chow diet HFD
100 ml water or WEGL at 2, 4 or 8%
(Everyday)
standard chow diet : 13.5% of energy from fat
high-fat diet ( HFD ) : 60% of energy from fat

11. WEGL prevents HFD-induced obesity in mice

12. Adipose size and liver lipid content
oil red O staining : lipid Dye
WEGL prevent HFD-induce obesity and decrease adipose size and liver lipid content

13. Pro-inflammation cytokines
Obesity
Insulin resistance
Imflammation
Intestinal integrity
Pro-inflammation cytokines
Gut microbiota
Endotoximia
(LPS)
TLR4

14. Detect inflammation gene in HFD-fed mice with WEGL
Pro-inflammatory cytokines
Anti-inflammatory cytokines
TNF-α, IL-1β, IL-6, PAI-1
IL-10
Measure messenger RNA of hepatic and adipose

15. Pro-inflammatory cytokines

16. Anti-inflammatory cytokines
WEGL reduces inflammation gene expression in HFD-fed mice

17. Pro-inflammation cytokines
Obesity
Insulin resistance
Imflammation
Intestinal integrity
Pro-inflammation cytokines
Gut microbiota
Endotoximia
(LPS)
TLR4

18. WEGL reduce serum endotoximia

19. Pro-inflammation cytokines
TLR4
JNK
IKK-β
IKB- α
phopholation
NFk-β
Pro-inflammation cytokines

20. WEGL reduces endotoxemia and insulin resistance in HFD mice

21. Pro-inflammation cytokines
Obesity
Insulin resistance
Imflammation
Intestinal integrity
Pro-inflammation cytokines
Gut microbiota
Endotoximia
(LPS)
TLR4

22. Classification of mice with WEGL or not

23. WEGL alters gut microbiota composition in HFD-fed mice

25. WEGL faecal transplants reduce obesity
transferred the microbiota of WEGL-treated mice to HFD-fed mice
Chow->HFD
HFD->HFD
Chow+8% WEGL ->HFD
HFD+8% WEGL ->HFD

26. Compare with different organ weight
Obesity and fat accumulation are reversed by faecal transplantation from WEGL-treated mice to HFD-fed mice

27. Analysis pro-inflammatory cytokines following faecal transplantation from WEGL-treated mice

28. Gut microbiota influence intestinal integrity in HFD mice
Gut microbiota decrease tight-junction protein in HFD mice

29. Analysis of gut microbiota following faecal transplantation

30. Analysis of gut microbiota following faecal transplantation

31. Polysaccharides analysed from a WEGL

32. Effect of WEGL polysaccharide fractions on body weight and fat accumulation in HFD-fed mice

33. Summary
Ganoderma lucidum can reduce obesity.
Polysaccharide of WEGL play a important role of reduce obesity.