metabolic stress, inflammation, and cancer

lecture 2, prof zani

adipocytes

• fat cells

• white adipose tissue (WATs) are most common

WAT function

• release signals into blood for communication

• eg leptin is secreted to tell you ur full

where are WATs found in body?

all over

• face

• mamary

• visceral in chest and abdomen

• subcutaneous areas

• bone marrow

obesity 

excessive fat accumulation that presents a health risk

35% rate in canada

BMI vs alternatives

• very convenient but not an accurate indication of health

• mass/height squared

• dexa scans and waist-hip ratios are more accurate

what does obesity increase the risk of

• inflammation

• cardiovasuclar disease

• diabetes

• 13 types of cancer

obesity impact on adipose tissue function

• inflammation makes it hard for WAT to store energy well

• can develop fatty liver

• size and quanittiy of adipocytes increases

cancer cells impact on adipocytes

• corrupt adipocytes and convince them to release lipids and endocrine factors to be used for metastisizing and prolifeeration

why is prof zani choosing to look at pancreatic cancer

• PC invades WAT

• adipocytes can infiltrate the pancreas

• PC is linked to obesity

what are KVAT

genetically engineered mice

how are KVAT being studied for PC and adipocyte interaciton?

• isolated PC tissue cells from KVAT are given tissue calcium feed

  • there was sufficient growth w/o adipocytes

• now given poor feed with access to adipocytes

  • PC cells proliferate more than before

what impact does an adipocyte conditioned medium have on PC cell growth? why?

• promotes cell growth

• could be 

  • cancer cells corrupting adipocytes

  • adipocytes release endocrine factors on their own that can be taken advantage of

which adipocyte secreted factors help the cancerous cells?

• metabolites such as polar sugars and amino acids were identified in the adipocyte conditioned medium

does obesity increase the amount of metabolies secreted by adipocytes

we’re looking into it

how do artifical sweeteners work?

• they activate the sweet taste receptor but we cannnot digest them

• have sucralose which is 600 more times sweet than sucrose

• 0 caloried

sweet taste receptor

• key receptor is a 2 unit G-coupled protein receptor

  • T1R2 and T1R3

• present in many cells, not just mouth

what do sweeteners increase risk of?

• cancer

• cerebrovascular events

• coronary heart disease

sucralose impact on T cells

• dampens T cell (CD4+ and CD8+) proliferation

• delays tumour rejection (autoimmunity)

how did Zani confirm that sucralose is really whats impacting T cell function?

• test tumour growth in 2 mice: one immunodeficient (no t cells) and one immunocompetent

• in the tcell lacking mouse, the tumour growth was the same with our without sucralose

• in the immunocompetent mouse, tumour growth increased with sucralose