臺灣博碩士論文加值系統

The hormone-stimulated lipolysis is a rapid way to mobilize fat from its storage depot for use in peripheral tissues. The only molecular mechanism considered so far is the activation of cellular lipases by β-adrenergic receptor (β-AR)/cAMP signal pathway to liberate fatty acids from triglycerides that are stored in lipid droplets (LDs) of cells. This study provides evidence showing that autophagy activity contributes in significant part to this stimulated lipolysis. The pharmacological inhibitors and the shRNA-based gene inhibition on the early or late autophagy reduce significantly the stimulated lipolysis. Upon β-AR activation, there is a marked increase in the autophagy-targeted LDs for lysosomal degradation, which is dependent on the LD-associated Rab7. Rab7 is physically interacts with perilipin, and this interaction is significantly enhanced by the β-activation. The dominant negative mutant of Rab7 not only abolishes its association with LDs but also eliminate the recruitment of autophagic components to LDs during the β-AR activation.

TABLE OF CONTENTS
ACKNOWLEDGEMENTS IV
ABSTRACT V
INTRODUCTION 1
MATERIALS AND METHODS 5
RESULTS 11
PART I. INHIBITION OF RAB7 EXPRESSION REDUCES β-AR/CAMP-STIMULATED LIPOLYSIS 11
PART II. AUTOPHAGIC ACTIVITY CONTRIBUTES TO β-AR-CAMP-STIMULATED LIPOLYSIS 14
PART III. β-AR ACTIVATION ENHANCES AUTOPHAGIC FLUX BY PROMOTING AUTOLYSOSOME FORMATION 16
PART IV. β-AR ACTIVATION INCREASES LIPOPHAGY-TARGETED LDS 19
PART V. RAB7 MEDIATES STIMULATORY EFFECTS OF β-AR ACTIVATION ON LIPOPHAGY 23
DISCUSSION 26
REFERENCES 30
FIGURES 38
ABBREVIATION LIST 94

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