Anti-Catabolic Effects Of Conjugated Linoleic Acid And Omega-3 Polyunsaturated Fatty Acid ...

126 Pages·2015·1.85 MB·English

Florida State University Libraries
Electronic Theses, Treatises and Dissertations The Graduate School
2012
Anti-Catabolic Effects of Conjugated
Linoleic Acid and Omega-3 Polyunsaturated
Fatty Acid Administration in Resting or
Loaded Skeletal Muscles of Middle Aged
Mice during 20 Weeks of High Fat Diet
Sang-Rok Lee
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THE FLORIDA STATE UNIVERSITY

COLLEGE OF HUMAN SCIENCES

ANTI-CATABOLIC EFFECTS OF CONJUGATED LINOLEIC ACID AND OMEGA-3
POLYUNSATURATED FATTY ACID ADMINISTRATION IN RESTING OR
LOADED SKELETAL MUSCLES OF MIDDLE AGED MICE
DURING 20 WEEKS OF HIGH FAT DIET

By

SANG-ROK LEE

A Dissertation submitted to the
Department of Nutrition, Food and Exercise Sciences
in partial fulfillment of the
requirements for the degree of
Doctor of Philosophy

Degree Awarded:
Spring Semester, 2012
Sang-Rok Lee defended this dissertation on March 23, 2012.

The members of the supervisory committee were:

Jeong-Su Kim

Professor Directing Dissertation

Samuel C Grant
University Representative

Lynn B Panton
Committee Member

The Graduate School has verified and approved the above-named committee members,
and certifies that the dissertation has been approved in accordance with university
requirements.
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I dedicate this dissertation to my mom and dad Bok-ae Kim and Kwan-hae Lee, my wife, Eun-sook
Yoo, and my daughters, Erin and Annie. Mom and dad, you have been a great influence in my life.
You have always supported my aspirations and prayed for my future success. From the beginning,
you have taught me to live within God. My wife, Eun-sook, you have always stood by me through
thick and thin. Without a doubt, nothing could have been completed without your love and dedication.
I thank God you are my wife. Erin and Annie, you have become the reason for my life. I always
thank GOD for sending you to me. Like my parents did, I will do all that I can for your future.

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ACKNOWLEDGEMENTS
The author wishes to thank the following people for their involvement in this dissertation:
My major professor and advisor, Dr. Jeong-Su Kim. I cannot find the words to express
my gratitude for your incredible dedication. Since I joined your lab, you have always been
invested in my educational growth and development as a scientist throughout my PhD program.
Not only as an academic mentor, but you have provided guidance on the right way for living
within Jesus. It has been an honor to be your doctoral student and I will never forget your
commitment and priceless efforts.
My committee member Dr. Panton. I sincerely thank you for everything you have done
for me throughout my time in the PhD program. You always have treated me like family and it
was a great opportunity to have you on my committee. Your outstanding insight and advice
enhanced the quality of my dissertation. I will never forget your generosity and dedication.
My committee member Dr. Samuel Grant. Thank you for being one of my committee
members and for providing the opportunity to work in one of the greatest research institutes in
the world. You have provided great insight and direction for my dissertation. It was my honor to
collaborate with your laboratory and I will remember all of your advice and dedication.
To my colleagues in the Kim muscle lab. It has been a pleasure to work with this lab
team. Eddie and Andy, I know that I could not complete my dissertation without your dedication.
You have always helped to ensure that my research was completed well. I will never forget your
great contribution and time spending with you. Mike and Dr. Park, I thoroughly enjoyed working
with both of you, I really appreciated the support you provided for my dissertation.
To my colleague Ihssann. I truly appreciate your hard work and dedication for my
dissertation. It would have been hard to complete this project without your incredible efforts. I
will remember your great help.
Dr. Michael Ormsbee, I sincerely appreciate your help on this research project, especially
for providing the supplements. Your help allowed my dissertation to go smoothly. Thank you.
To my colleagues Neema, Shrin, and Marcus. Thanks for everything you have done for
my dissertation. I sincerely appreciate your dedication.
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Finally and most importantly, I would like to thank my savior and Lord Jesus Christ. I
believe you always have been with me. You are the only way to solve the things given to me and
get through the tribulations I have encountered.

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TABLE OF CONTENTS
LIST OF TABLES ....................................................................................................................... viii
LIST OF FIGURES ....................................................................................................................... ix
ABSTRACT ................................................................................................................................... xi
1. CHAPTER ONE: INTRODUCTION ..................................................................................1
1.1 SIGNIFICANCE OF STUDY .......................................................................................3
1.2 SPECIFIC AIMS ...........................................................................................................3
1.3 RESEARCH HYPOTHESES ........................................................................................4
1.4 ASSUMPTIONS ...........................................................................................................4
1.5 DELIMITATIONS ........................................................................................................4
1.6 LIMITATIONS .............................................................................................................5
1.5 DEFINITIONS OF TERMS ..........................................................................................5
2. CHAPTER TWO: REVIEW OF RELATED LITERATURE .........................................7
2.1 AGE-MEDIATED IMPAIRMENTS AND SARCOPENIA .........................................7
2.1.1 Hormonal changes and sarcopenia.....................................................................7
2.1.2 Alterations of motor unit and sarcopenia ...........................................................7
2.1.3 Oxidative stress-mediated mitochondria impairments and sarcopenia ..............8
2.1.4 Oxidative stress-mediated apoptosis and sarcopenia .........................................9
2.2 INFLAMMATION-MEDIATED IMPAIRMENTS AND MUSCLE WASTING .....10
2.2.1 Pro-and anti-inflammatory cytokines ..............................................................10
2.2.2 Chronic low-grade inflammation during aging................................................12
2.2.3 Chronic inflammation-related diseases and muscular abnormalities in aged
populations .......................................................................................................13
2.3 SARCOPENIC OBESITY ...........................................................................................14
2.3.1 High fat diet-induced obesity ...........................................................................14
2.3.2 Inflammation-induced changes in body composition and disability
During aging ....................................................................................................15
2.3.3 Sarcopenic obesity and inflammatory cytokines-mediated insulin resistance .15
2.3.4 Sarcopenic obesity and adipokine-induced insulin resistance .........................19
2.4 INFLAMMATION-MEDIATED SARCOPENIA ......................................................21
2.4.1 Inflammatory cytokine-induced impairments in anabolic systems and
sarcopenia ........................................................................................................21
2.4.2 TNF-α-mediated apoptosis and sarcopenia......................................................24
2.5 EXERCISE-INDUCED CHANGES IN INFLAMMATION LEVEL AND
SARCOPENIA ......................................................................................................................24
2.5.1 Aerobic-exercise training and inflammation in aged muscle ..........................24
2.5.2 Resistance-exercise training and inflammation in aged muscle ......................25
2.6 ANTI-INFLAMMATORY SUPPLEMENTS AND SARCOPENIA .........................28
2.6.1 Conjugated linoleic acid and inflammation in aged muscle ............................28
2.6.2 Omega-3 poly unsaturated fatty acid and inflammation in aged muscle .........29
2.7 MAGNETIC RESONANCE IMAGING TRACKING CHANGES IN SKELETAL
MUSCLE ...............................................................................................................................31
2.7.1 Diffusion-weighted MR imaging .....................................................................31
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2.8 SUMMARY AND FUTURE RESEARCH IMPLICATIONS....................................32
3. CHAPTER THREE: RESEARCH DESIGN AND METHODS.....................................33
3.1 OVERVIEW OF EXPERIMENTAL DESIGN ...........................................................33
3.2 RESISTANCE EXERCISE TRAINING .....................................................................33
3.3 CLA/N-3 MIX ADMINISTRATION ..........................................................................34
3.4 SPECIFIC AIM 1 (BODY COMPOSITION AND MYOFIBER DIMENSIONS) ....35
3.5 SPECIFIC AIM 2 (NEUROMUSCULAR FUNCTIONALITY) ................................36
3.6 SPECIFIC AIM 3 (MUSCLE MRNA EXPRESSION)...............................................37
3.7 STATISTICAL ANALYSIS AND SAMPLE SIZE DETERMINATION .................39
4. CHAPTER FOUR: RESULTS ...........................................................................................40
4.1 FOOD AND CLA/N-3 CONSUMPTION ...................................................................40
4.2 MORBIDITY AND MORTALITY .............................................................................40
4.3 DUAL X-RAY ABSORPTIOMETRY DETERMINED BODY COMPOSITION ....42
4.4 NEUROMUSCULAR FUNCTIONALITY ................................................................46
4.5 MYOFIBER DIMENSIONS .......................................................................................49
4.6 MUSCLE MASS ........................................................................................................51
4.7 CHANGES IN TRANSCRIPT FACTORS .................................................................55
5. CHAPTER FIVE: DISCUSSION ......................................................................................77
5.1 MORBIDITY AND MORTALITY .............................................................................77
5.2 BODY COMPOSITION ..............................................................................................78
5.3 MUSCLE MASS AND MYOFIBER DIMENSIONS ................................................81
5.4 MUSCLE STRENGTH AND SENSORIMOTOR FUNCTION ................................82
5.5 REGULATOR OF INFLAMMATION .......................................................................83
5.6 REGULATORS OF PROTEIN TURNOVER ............................................................85
5.7 REGULATORS OF MITOGENESIS .........................................................................86
5.8 REGULATORS OF MYOGENESIS ..........................................................................87
5.9 CONCLUSIONS..........................................................................................................87

APPENDICES ..............................................................................................................................89
ANIMAL CARE AND USE COMMITTEE APPROVAL OF STUDY PROTOCOL ........89
REFERENCES .............................................................................................................................90

BIOGRAPHICAL SKETCH ....................................................................................................113

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LIST OF TABLES
1. Profile of diets .......................................................................................................................41

2. Daily food and energy consumption ......................................................................................42

3. DXA determined body composition ......................................................................................42

4. Neuromuscular functionality measurements .........................................................................46

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LIST OF FIGURES
1. Comparison of Total Body Mass ...........................................................................................43

2. Comparison of Lean Body Mass ...........................................................................................44

3. Comparison of Fat Mass ........................................................................................................45

4. Grip Strength Test .................................................................................................................47

5. Incline Plane Test ..................................................................................................................48

6. Fractional anisotropies ...........................................................................................................49

7. Eigenvalues (λ) 1, β, and γ ....................................................................................................50

8. Gastrocnemius muscle wet weight ........................................................................................51

9. Soleus muscle wet weight .....................................................................................................52

10. Quadriceps muscle wet weight ..............................................................................................53

11. Hamstring muscle wet weight ...............................................................................................54

12. Relative mRNA expression of TNF-α in the gastrocnemius .................................................55

13. Relative mRNA expression of TNF-α in the quadriceps ......................................................56

14. Relative mRNA expression of IL-1(cid:533) in the gastrocnemius ...................................................57

15. Relative mRNA expression of IL-1(cid:533) in the soleus ................................................................58

16. Relative mRNA expression of IL-1(cid:533) in the quadriceps ........................................................59

17. Relative mRNA expression of IL-6 in the gastrocnemius .....................................................60

18. Relative mRNA expression of IL-6 in the soleus ..................................................................61

19. Relative mRNA expression of IL-6 in the quadriceps ..........................................................62

20. Relative mRNA expression of IL-15 in the gastrocnemius ...................................................63

21. Relative mRNA expression of IL-15 in the soleus ................................................................64

22. Relative mRNA expression of Akt in the quadriceps ...........................................................65

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