EFFECT OF ETHANOL ON AUTOPHAGY OF SKELETAL MUSCLE

Authors' Affiliations

Lyndsey Hagood1 and Dr. Jonathan Peterson2 1Department of Biomedical Sciences, College of Arts and Sciences, 2College of Public Health, Department of Health Sciences, East Tennessee State University, Johnson City, Tennessee

Location

Ballroom

Start Date

4-5-2018 8:00 AM

End Date

4-5-2018 12:00 PM

Poster Number

86

Name of Project's Faculty Sponsor

Jonathan Peterson

Faculty Sponsor's Department

Department of Health Sciences

Classification of First Author

Graduate Student-Master’s

Type

Poster: Competitive

Project's Category

Biomedical and Health Sciences

Abstract or Artist's Statement

Introduction: Autophagy is a complex and highly regulated process responsible for the maintenance of cellular homeostasis and the degradation and recycling of key nutrients. Autophagy is generally believed to serve a protective role, responding to periods of starvation and aging, pathogen invasion, development, improper protein folding, and organelle damage. Defective autophagy, on the other hand, is implicated in disease states such as metabolic syndrome, hepatic steatosis, obesity, and atherosclerosis, among others. Interestingly, in various skeletal muscle diseases associated with either atrophy or dystrophy, the accumulation of autophagosomes within myofibers is a common feature. Additionally, modulation of autophagy in skeletal muscle has been reported to influence energy and lipid metabolism, while also affecting these parameters in organs such as the pancreas, liver, and adipose tissue. Ethanol consumption inhibits protein synthesis while simultaneously inducing proteolysis of skeletal muscle, and a decreased skeletal muscle mass correlates to heightened disease progression in patients such as those diagnosed with alcoholic cirrhosis and various cancers. Due to the correlation between skeletal muscle loss and exacerbated disease progression, the role of autophagy in response to ethanol consumption could highlight new therapeutic modalities that may attenuate disease progression and improve final presentation of various disease states. Further, acute ethanol consumption has shown a selectivity of autophagy toward mitochondria and lipid droplets, rather than proteins that are typically degraded during starvation. Due to ethanol’s damaging effects exerted on mitochondria and lipid peroxidation, removal of mitochondria and lipid droplets via autophagy could represent an attempt at host defense. One limitation of various studies analyzing autophagy in skeletal muscle is the duration of ethanol exposure. Therefore, we aimed to characterize skeletal muscle autophagic flux in both the NIAAA, 10-day ethanol model as well as the chronic, six-week ethanol model.

Methods: In order to analyze autophagic flux in response to ethanol consumption, C57BL/6 mice were treated with either a control or ethanol diet (5% EtOH/vol) for a period of ten days (NIAAA model) or six weeks (chronic model). Mice were then euthanized and hindlimb skeletal muscles were collected, snap frozen, and analyzed using an immunoblot assay.

Results: Markers indicative of autophagy, such as autophagy-related genes (Atg), Beclin-1, and LC3A/B, are expected to exhibit increased expression in response to ethanol consumption in both the NIAAA and chronic ethanol model.

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Apr 5th, 8:00 AM Apr 5th, 12:00 PM

EFFECT OF ETHANOL ON AUTOPHAGY OF SKELETAL MUSCLE

Ballroom

Introduction: Autophagy is a complex and highly regulated process responsible for the maintenance of cellular homeostasis and the degradation and recycling of key nutrients. Autophagy is generally believed to serve a protective role, responding to periods of starvation and aging, pathogen invasion, development, improper protein folding, and organelle damage. Defective autophagy, on the other hand, is implicated in disease states such as metabolic syndrome, hepatic steatosis, obesity, and atherosclerosis, among others. Interestingly, in various skeletal muscle diseases associated with either atrophy or dystrophy, the accumulation of autophagosomes within myofibers is a common feature. Additionally, modulation of autophagy in skeletal muscle has been reported to influence energy and lipid metabolism, while also affecting these parameters in organs such as the pancreas, liver, and adipose tissue. Ethanol consumption inhibits protein synthesis while simultaneously inducing proteolysis of skeletal muscle, and a decreased skeletal muscle mass correlates to heightened disease progression in patients such as those diagnosed with alcoholic cirrhosis and various cancers. Due to the correlation between skeletal muscle loss and exacerbated disease progression, the role of autophagy in response to ethanol consumption could highlight new therapeutic modalities that may attenuate disease progression and improve final presentation of various disease states. Further, acute ethanol consumption has shown a selectivity of autophagy toward mitochondria and lipid droplets, rather than proteins that are typically degraded during starvation. Due to ethanol’s damaging effects exerted on mitochondria and lipid peroxidation, removal of mitochondria and lipid droplets via autophagy could represent an attempt at host defense. One limitation of various studies analyzing autophagy in skeletal muscle is the duration of ethanol exposure. Therefore, we aimed to characterize skeletal muscle autophagic flux in both the NIAAA, 10-day ethanol model as well as the chronic, six-week ethanol model.

Methods: In order to analyze autophagic flux in response to ethanol consumption, C57BL/6 mice were treated with either a control or ethanol diet (5% EtOH/vol) for a period of ten days (NIAAA model) or six weeks (chronic model). Mice were then euthanized and hindlimb skeletal muscles were collected, snap frozen, and analyzed using an immunoblot assay.

Results: Markers indicative of autophagy, such as autophagy-related genes (Atg), Beclin-1, and LC3A/B, are expected to exhibit increased expression in response to ethanol consumption in both the NIAAA and chronic ethanol model.