EXAM Lecture 18

Question 1

SCFA transport across the epithelial barrier

Answer 1

apical membrane transporters (from lumen into cell):
- MCT1, SMCT1

basolateral membrane transporters (out of cell and into systemic circulation):
- MCT4, MCT5

Question 2

SCFA signalling in host tissues

Answer 2

G coupled protein receptors (GPRs), all SCFA can bind to them but theres some preference

B-butyrate P-proprionate A-acetate

GPR41 (FFAR3) binds B=P > A
GPR43 (FFAR2) binds A=P > B
GPR109a (niacin receptor 1) B > and longer SCFA
OLFR78 A and P

Effects:
in the WAT:
- decreased hormone sensitive lipase activity
- decreased FFA release into blood (GOOD)
- increased leptin secretion (BAD)

in brown adipose tissue:
- increased fatty acid oxidation (GOOD)

in liver:
- increased fatty acid oxidation and decreased fatty acid synthesis (GOOD)

in skeletal muscle:
- increased fatty acid oxidation (GOOD)

metabolic effects: P decreases lipogenesis, A used to make acetyl CoA

in all tissues:
- decreased NFkB. TNFa, FOXP3 (GOOD)
- increased anti inflammatory IL10 (GOOD)

Question 3

SCFA (specifically butyrate) and gut barrier function

Answer 3

• inhibits NFkB pathway
• decrease colonic pH thereby decreasing growth of pathogenic bacteria
• enhances intestinal barrier function (increases tight junction assembly)
• enhances epithelial barrier defence mechanisms by stimulating production of:
  – MUC2
  – IgA
  – Tre-foil factor 3 (TFF3)

Question 4

what happens with prebiotic fiber supplementation in obesity (oligofructose)

Answer 4

increased L cell # and portal plasma GLP-1 and decreased LPS
- involved in gut barrier function and glucose homestasis

“still obese but attenuated symptoms”

Question 5

what bacteria may play a role in gut barrier being compromised in obesity

Answer 5

AKKERMANSIA MUCINIPHILA (anti obesity bacteria)

lean:
- lots of akkermansa
- thick mucus
- tight junctions

obese
- decreased akkermansa
- decreased intestinal barrier integrity
- increased inflammation

PREbiotic supplementation on HFD (oligofructose)
- increases depleted akkerrmansa muciniphila
- reduces fat mass/ serum LPS
- reduces M1 macrophage infiltration into adipose tissue

PRObiotic supplementation on HFD (HF-Akk)
- reduces fat mass/ serum LPS
- increases barrier integrity, mucus production, Reg3g
- reduces M1 macrophage infiltration
- reduces fasting blood glucose and insulin resistance

overall: akkermansia muciniphila inversely correlates with the onset of inflammation, aletered adipose tissue metabolism, and metabolic disorders during obesity in mice
- metabolic parameters improved in human trials but gut microbiota composition unchanged after three months (doesnt colonize therefore would have to take it every day)

Question 6

Beans and obesity

Answer 6

beans increase SCFA (acetate, propionate, butyrate)

beans increased akkermansia muciniphila 15 fold
- restored obese epithelial and mucus barrier
- decreased adipose tissue inflammatory mediator production

beans increase ZO-1, occludin, claudin-2

beans improve epithelial barrier integrity in obesity
- measured by lowered FITC dextran levels (means there was less movement of it across barrier)

beans reduce adipose inflammation
- increased IL-6, MCP-1, leptin, adiponectin
- decreased STAT3