Presentation Hip Joint By: Aaron White, Ashley Garbarino, Anna Mueller.
Ashley Kang - Presentation
-
Upload
ashley-kang -
Category
Documents
-
view
57 -
download
1
Transcript of Ashley Kang - Presentation
Ashley KangFaculty Advisor: Andreas Stahl, PhD
School of Public HealthHonors ThesisMay 16, 2016
The Effect of Coenzyme Q (CoQ) on Beige Adipogenesis in a
Human Cell Model
WAT, BAT, Beige adipocytes• White adipose tissue (WAT)
– Large lipid droplet with few mitochondria– Major depository for energy in lipid form
• Brown adipose tissue (BAT)– Smaller lipid droplets, rich in mitochondria
• Expression of Uncoupling protein 1 (Ucp1)– Main source of energy expenditure via uncoupling of oxygen
consumption from ATP production• Dissipates chemical energy to generate heat
• Beige adipocytes– Clusters of Ucp1-expressing adipocytes (like BAT) with
thermogenic capacity that develop in WAT depots
Sell et al., 2004
Coenzyme Q (CoQ) • Necessary component of
mitochondrial electron transport chain– Electron carrier from complex I
and II to complex III
• Longer isoprenyl side chains equate to a more hydrophobic molecule
• CoQ plays important role in brown adipocyte function– Increasing CoQ levels exogenously could be therapeutically
beneficial for a variety of metabolic diseases
Statins
• Most effective drugs in reducing elevated low-density lipoprotein (LDL) cholesterol– Can be classified into two groups: hydrophilic and lipophilic
• Atorvastatin is lipophilic
• Statins and CoQ share same precursor– Some studies suggest statins reduce endogenous
production of cholesterol and CoQ
Research Questions Can a human beige adipocyte model be established by
driving preadipocytes to differentiate into more beige adipocytes?
Given that CoQ is prevalent in BAT and that it can regulate Ucp1 levels in BAT and that statins may inhibit CoQ, will statins reduce Ucp1 expression in BAT? Subsequently, if we exogenously supplement CoQ, can it
rescue CoQ levels?
Hypothesis: We hypothesize that statin dependent decrease in Ucp1 expression in human beige cells is caused by CoQ deficiency, and supplementation of CoQ can rescue this inhibitory effect.
Courtesy of Dr. Ching-Fang Chang, PhD
Can we establish a human beige model?
• Intralipid treatment = difficult to accurately measure CoQ levels
• CoQ supplementation only increases levels at DIF D10-14 (4CBA/Ator) and not at Day -3-0• Suggested a receptor-dependent
CoQ uptake in mature adipocytes
• IL - stimulate differentiation / inhibit Ucp1 expression by promoting adipogenesis
Problems Using Intralipid (IL) Carrier
Using Micelle as New Carrier System
Conclusion Demonstrated that Atorvastatin and 4-CBA consistently
inhibited CoQ levels and Ucp1 expression in beige adipocytes
However, CoQ levels were neither efficiently nor effectively supplemented Question of whether CoQ supplementation can rescue
inhibitory effect could not be answered since results were inconclusive
Further research is necessary – many therapeutic benefits of CoQ supplementation, especially in protecting heart against mitochondrial dysfunction (diabetic cardiomyopathy / statin-induced myopathy)
Acknowledgments
The Stahl Lab• Dr. Andreas Stahl, PhD• Dr. Ching-Fang Chang, PhD• Dr. Jiehan Li, PhD• Kevin Tharp• Michael Park• Brittney Bivins • Hyo Min Park• Lacey Andrews
PH195• Dr. Charlotte Smith, PhD• Dr. Maureen Lahiff, PhD