HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: db07-0510v1 56/12/2973    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Koh, E. H. Articles by Lee, K.-U. Search for Related Content PubMed PubMed Citation Articles by Koh, E. H. Articles by Lee, K.-U. Social Bookmarking                What's this?

Essential Role of Mitochondrial Function in Adiponectin Synthesis in Adipocytes

¹ Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
² Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea
³ Department of Pharmacology, University of Ulsan College of Medicine, Seoul, Korea
⁴ Department of Anatomy, College of Medicine, Inha University, Incheon, Korea
⁵ Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California

Address correspondence and reprint requests to Ki-Up Lee, MD, Department of Internal Medicine, University of Ulsan College of Medicine, Poongnap-dong, Songpa-ku, Seoul 138-736, Korea. E-mail: kulee{at}amc.seoul.kr

Abbreviations: Ad-NRF-1, adenovirus-mediated overexpression of nuclear respiratory factor 1; ATF, activating transcription factor; ATP, adenosine triphosphate; CCCP, carbonyl cyanide m-chlorophenylhydrazone; ER, endoplasmic reticulum; JNK, c-Jun NH₂-terminal kinase; mtDNA, mitochondrial DNA; mtTFA, mitochondrial transcription factor A; NRF, nuclear respiratory factor; ORP150, 150-kDa oxygen-regulated protein; PPAR, peroxisome proliferator–activated receptor; ROS, reactive oxygen species; siRNA, small interfering RNA; TNF, tumor necrosis factor; TZD, thiazolidinedione; XBP, X-box binding protein

OBJECTIVE—Adiponectin is an important adipocytokine that improves insulin action and reduces atherosclerotic processes. The plasma adiponectin level is paradoxically reduced in obese individuals, but the underlying mechanism is unknown. This study was undertaken to test the hypothesis that mitochondrial function is linked to adiponectin synthesis in adipocytes.

RESEARCH DESIGN AND METHODS—We examined the effects of rosiglitazone and the measures that increase or decrease mitochondrial function on adiponectin synthesis. We also examined the molecular mechanism by which changes in mitochondrial function affect adiponectin synthesis.

RESULTS—Adiponectin expression and mitochondrial content in adipose tissue were reduced in obese db/db mice, and these changes were reversed by the administration of rosiglitazone. In cultured adipocytes, induction of increased mitochondrial biogenesis (via adenoviral overexpression of nuclear respiratory factor-1) increased adiponectin synthesis, whereas impairment in mitochondrial function decreased it. Impaired mitochondrial function increased endoplasmic reticulum (ER) stress, and agents causing mitochondrial or ER stress reduced adiponectin transcription via activation of c-Jun NH₂-terminal kinase (JNK) and consequent induction of activating transcription factor (ATF)3. Increased mitochondrial biogenesis reversed all of these changes.

CONCLUSIONS—Mitochondrial function is linked to adiponectin synthesis in adipocytes, and mitochondrial dysfunction in adipose tissue may explain decreased plasma adiponectin levels in obesity. Impaired mitochondrial function activates a series of mechanisms involving ER stress, JNK, and ATF3 to decrease adiponectin synthesis.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?