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Characterization of Feline Adiponectin and Its Association with Metabolic Indices in Lean and Obese Cats

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Characterization of Feline Adiponectin and Its Association with Metabolic Indices in Lean and Obese Cats University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 8-2009 Characterization of Feline Adiponectin and its Association with Metabolic Indices in Lean and Obese Cats Angela Lea Lusby University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Medicine and Health Sciences Commons Recommended Citation Lusby, Angela Lea, "Characterization of Feline Adiponectin and its Association with Metabolic Indices in Lean and Obese Cats. " PhD diss., University of Tennessee, 2009. https://trace.tennessee.edu/utk_graddiss/72 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Angela Lea Lusby entitled "Characterization of Feline Adiponectin and its Association with Metabolic Indices in Lean and Obese Cats." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Comparative and Experimental Medicine. Claudia Kirk, Major Professor We have read this dissertation and recommend its acceptance: Joseph Bartges, Stephen Kania, Nicholas Frank, Naima Moustaid-Moussa, Jon Wall Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) To the Graduate Council: I am submitting herewith a dissertation written by Angela Lea Lusby entitled “Characterization of Feline Adiponectin and its Association with Metabolic Indices in Lean and Obese Cats.” I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Comparative and Experimental Medicine. Claudia Kirk, Major Professor We have read this dissertation and recommend its acceptance: Joseph Bartges Stephen Kania Nicholas Frank Naima Moustaid-Moussa Jon Wall Acceptance for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School 1 Characterization of Feline Adiponectin and its Association with Metabolic Indices in Lean and Obese Cats A Dissertation Presented for the Doctor of Philosophy Degree The University of Tennessee, Knoxville Angela Lea Lusby August 2009 Copyright © 2009 by Angela Lea Lusby All rights reserved. ii ACKNOWLEDGMENTS I thank all those who helped me complete my Doctor of Philosophy degree in Comparative and Experimental Medicine. I specifically thank Dr. Claudia Kirk for her mentorship throughout my graduate work, and Dr. Stephen Kania for his guidance and support of my laboratory research. I also thank the other members of my committee, Dr. Joseph Bartges, Dr. Nicholas Frank, Dr. Naima Moustaid-Moussa, and Dr. Jon Wall for their advice and encouragement. The staff of the University of Tennessee’s clinical virology, immunology, and endocrinology laboratories, specifically Dr. Mohamed Abd-Eldaim and Ms. Diane Trent, were also instrumental in my training. I would also like to thank the wonderful veterinary technicians who helped with this project, Ms. Tammy Moyers, Ms. Hannah Byrd, and Ms. Gina Galyon. I am grateful for the financial support Nestlé Purina PetCare Company and the Morris Animal Foundation provided for this project. Lastly, I would like to thank my family, friends, and most importantly, my husband James. Their unwavering support and encouragement made this work possible. iii ABSTRACT Adipose tissue secretes over 100 different proteins and cytokines called adipokines. Adiponectin is one of the most intriguing adipokines because it is closely associated with insulin sensitivity and is an early marker for Type-2 diabetes mellitus in human beings. Cats are at risk for developing Type-2 diabetes with obesity, so it is important for researchers to understand the role adipokines, like adiponectin, play in feline metabolism. This project sought to lay the foundation for future research regarding feline adiponectin by sequencing adiponectin cDNA, measuring adiponectin’s expression in various tissues, validating and developing new techniques for measuring adiponectin in circulation, determining the influence of gender on adiponectin concentrations, and by monitoring changes in adiponectin as cats gain and lose fat mass. The results of this project revealed that adiponectin has a similar cDNA and amino acid sequence to other species and is secreted almost exclusively from adipose tissue. However, cats differed from other species in that visceral adipose tissue had more adiponectin expression than subcutaneous adipose tissue. Serum feline adiponectin was measured using a commercially available murine adiponectin ELISA, and the high molecular weight (HMW) form was detected using gel chromatography combined with ELISA. Neutered male cats may have lower concentrations of total adiponectin than female cats and lower percentages of HMW adiponectin than all other gender groups. Similar to humans, HMW adiponectin was more closely associated with improved glucose metabolism than total adiponectin. HMW adiponectin also correlated more closely with body fat mass than total adiponectin. Despite some unique characteristics, feline adiponectin appears similar in structure and function to adiponectin in other species. iv TABLE OF CONTENTS CHAPTER I........................................................................................................................ 1 INTRODUCTION .............................................................................................................. 1 Project Summary .............................................................................................................. 1 Adipose Physiology ........................................................................................................... 2 Adipose Development................................................................................................. 2 Adipose Anatomy ....................................................................................................... 3 Endocrine Functions of Adipose................................................................................. 5 Leptin ...................................................................................................................... 5 Tumor Necrosis Factor – alpha............................................................................. 15 Resistin.................................................................................................................. 16 Visfatin.................................................................................................................. 17 Interleukin-6.......................................................................................................... 18 Adiponectin........................................................................................................... 19 Role of Insulin in Metabolism ........................................................................................ 32 Insulin Secretion and Regulation.............................................................................. 33 Carbohydrate metabolism ......................................................................................... 35 Lipid Metabolism...................................................................................................... 36 Protein Metabolism................................................................................................... 37 Pathogenesis of Insulin Resistance and Type-2 Diabetes Mellitus ............................. 37 Glucotoxicity............................................................................................................. 38 Lipotoxicity............................................................................................................... 41 Amyloidosis .............................................................................................................. 42 Adipokines and Inflammation................................................................................... 44 Feline Metabolism and Insulin Resistance ................................................................... 45 Metabolic Adaptations in the Cat ............................................................................. 45 Feline Diabetes.......................................................................................................... 47 Pathogenesis.......................................................................................................... 48 Diagnosis............................................................................................................... 50 Insulin sensitivity testing ...................................................................................... 52 CHAPTER II..................................................................................................................... 57 SEQUENCING OF FELINE ADIPONECTIN ................................................................ 57 Introduction ....................................................................................................................
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