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Start Date

8-5-2020 12:00 AM

Document Type

Oral Presentation

Advisor

Aaron Brown, PhD

Abstract

Accumulation of excess fat in white adipose tissue (WAT) is associated with an increase in risk for type 2 diabetes, stroke and heart disease. Unlike WAT, brown adipose tissue (BAT) is unique in that it is able to burn calories by converting chemical energy directly into heat (termed thermogenesis) when activated by the sympathetic nervous system during cold exposure. Unfortunately, attempts at modifying obesity in humans by stimulating BAT with drugs has largely been unsuccessful. One potential alternative to drugs is to generate cell-based therapies to supplement obese patients with additional BAT. However, studies have shown that transplanted BAT turns into energy storing white-like adipocytes over time. In this work, we test the feasibility of using optogenetics for long-term activation of BAT. Optogenetics is a technique that involves the use of light to control signaling in cells that have been genetically modified to express light-sensitive proteins. The goals of this project were to (1) set up the necessary ontogenetic equipment for blue light stimulation, (2) create genetically modified brown adipose precursor cell lines that express a bacterial-derived photo-inducible adenylyl cyclase (bPAC) and (3) test the feasibility of stimulating signaling downstream of adenylyl cyclase after blue light stimulation. We found that blue light stimulation of the bPAC led to a marked increase in cAMP production similar to forskolin, a drug that is commonly used to activate cultured brown adipocytes.

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Sophia Blanchard Presentation Transcript

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May 8th, 12:00 AM

Photo-inducible energy expenditure as a treatment for metabolic disease

Accumulation of excess fat in white adipose tissue (WAT) is associated with an increase in risk for type 2 diabetes, stroke and heart disease. Unlike WAT, brown adipose tissue (BAT) is unique in that it is able to burn calories by converting chemical energy directly into heat (termed thermogenesis) when activated by the sympathetic nervous system during cold exposure. Unfortunately, attempts at modifying obesity in humans by stimulating BAT with drugs has largely been unsuccessful. One potential alternative to drugs is to generate cell-based therapies to supplement obese patients with additional BAT. However, studies have shown that transplanted BAT turns into energy storing white-like adipocytes over time. In this work, we test the feasibility of using optogenetics for long-term activation of BAT. Optogenetics is a technique that involves the use of light to control signaling in cells that have been genetically modified to express light-sensitive proteins. The goals of this project were to (1) set up the necessary ontogenetic equipment for blue light stimulation, (2) create genetically modified brown adipose precursor cell lines that express a bacterial-derived photo-inducible adenylyl cyclase (bPAC) and (3) test the feasibility of stimulating signaling downstream of adenylyl cyclase after blue light stimulation. We found that blue light stimulation of the bPAC led to a marked increase in cAMP production similar to forskolin, a drug that is commonly used to activate cultured brown adipocytes.

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