EXAM Lecture 15

Question 1

Bean bioactives and gut health

Answer 1

non digestible components (bean bioactives) get fermented in colon:
- slowly digestible starch
- resistant starch
- insoluble fiber
- soluble fiber
- phenolic compounds

• are microbial substrates that produce SCFAs; influence epithelial barrier function/integrity
• can alter microbiota composition
• reduces immune and inflammatory responses
• decreases IBD, obesity, colonc cancer

Question 2

Effects of bean supplementation on mucosal barrier defense

Answer 2

increased SCFA
- anti inflammatory microbial fermentation products

enhanced epithelial barrier integrity
- reduced bacterial translocation (blood LPS levels)

• increased Muc2 mucus layer thickness
• increased tight junctions
• increased anti microbial and anti inflammatory defense (IgA, REG3y)

Question 3

Obesity

Answer 3

state of low grade chronic inflammation
- blood levels of inflammatory mediators change in obese individuals
– increased LPS, inflammatory cytokines (TNFa, IL6, MCP1), leptin
– decreased adiponectin (mediator that helps decrease inflammation)

adipose tissue biopsies
- visceral adipose tissue (VAT)
- subcutaneous adipose tissue (less inflammatory but invasive vs VAT)

experimental mouse models for diet induced obesity
- high fat diet (HFD) induced obesity recapitulates critical features of the human obese phenotype

Question 4

Cellular source for inflammatory mediators in obesity

Answer 4

inflammatory mediators produced in obese adipose tissue impact susceptibility to or promote the development of other pathologies (why theres so many co morbidities)

cellular sources for inflammatory mediators:
- adipocytes AND immune cells in adipose tissue (specific types of immune cells will infiltrate the adipose tissue and influence its function)

• stimulated by:
  LPS/PGN from microbiota
  free saturated fatty acid (stimulate/bind to TLR2/4)
  inflammatory mediators themselves

Question 5

Overview of obese versus lean adipose tissue (AT)

with exam question

Answer 5

adipokine: a hormone or cytokine produced in AT (could either be an adipocyte or immune cell within AT)
EXAM: over 600 identified

Lean:
- adipogenesis intact (minimal hypertrophy)
- sufficient storage capacity
- functional adipose tissue
- metabolically healthy (no inflammation)
- insulin sensitive

obese:
- decreased adipogenesis; leads to adipocyte hypertrophy in abdomen, thorax, breasts (CENTRAL parts of body)
- dysfunctional adipose tissue:
– storage capacity compromised
– low grade inflammation
– insulin resistance
- INCREASED FFA (bind to TLR2/4 and increase cytokines)

Question 6

White adipose tissue (WAT) in obesity

Answer 6

excess calories stored as triglycerides in adipose tissue

over nutrition leads to adipose tissue remodelling as AT transitions from lean to obese
- adipocyte hypertrophy

• insufficient angiogenesis; cant supply enough oxygen to growing adipocytes - makes a hypoxic environment where adipocytes die by necrosis
• immune cell infiltration into the adipose tissue; increase immune cells and promotes inflammatory mediator secretion (increased macrophages, CD8 T+ cells, decreased Tregs)
• increased production of inflammatory mediators (produced from adipose tissue = adipokines)

Question 7

WAT and chronic inflammatory in obesity

Answer 7

adipokines and FFA from AT enter into the blood and impact function in other tissues

visceral WAT increases:
- TNFa
- IL6
- MCP1
- leptin
- FFA
decreases
- adiponectin

MCP-1 (macrophage chemoattractant protein) attracts more macrophages to the adipose tissue and causes IR

leads to:
- insulin resistance
- pro inflammatory and pro atherogenic mediators
- atherosclerosis and increased CVD risk
- adiponectin

Question 8

insufficient blood supply in obesity

Answer 8

in obesity, changes in dominant adipose tissue immune cell composition:
- increased chemokine expression recruiting immune cells to the adipose tissue (eg, MCP1 and many others) recruit more macrophages
- increase CD8 T+ cells (infiltrate AT first)
- increase M1 macrophages (infiltrate AT second)
M2 and Treg decreased

immune cells then cluster around an adipocyte:
- form a crown like structure (CLS)
- typically dead or necrotic adipocytes secrete many more inflammatory mediators
- M1 macrophages function to phagocytose the dying adipocyte and secrete MANY inflammatory mediators (TNFa, IL6, MCP1, leptin = THE BIG FOUR)
leptin comes from adipocyte, rest from immune cells

two slides I hand wrote