Essential role of mitochondrial function in adiponectin synthesis in adipocytes
Abstract
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 NH(2)-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.
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Mitochondria fulfill a crucial role in determining cellular, tissue, and systemic metabolic flexibility.
“Additionally, insulin secretion from pancreatic β cells (104) and synthesis and secretion of adipokines from WAT is dependent on mitochondrial function (105), suggesting that mitochondria fulfill a crucial role in determining cellular, tissue, and systemic metabolic flexibility.”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [105]
Among the mitochondrial functions that may be relevant for white adipose tissue function are the anaplerotic generation of metabolic intermediates for fatty acid synthesis and esterification, the maintenance of a robust pathway for the folding and secretion of high abundance circulating proteins such as adiponectin, and interactions between mitochondrial function and components of the insulin-sign
“Among the mitochondrial functions that may be relevant for white adipose tissue function are the anaplerotic generation of metabolic intermediates for fatty acid synthesis and esterification (159), the maintenance of a robust pathway for the folding and secretion of high abundance circulating proteins such as adiponectin (160), and interactions between mitochondrial function and components of the”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [160]
Decreased mitochondrial capacity in adipocytes may also alter adipocyte insulin sensitivity and/or function due to the high energetic requirements for fatty acid storage, adipokine secretion, insulin signaling, and glucose uptake.
“In addition to effects on fuel utilization, decreased mitochondrial capacity in adipocytes may also alter adipocyte insulin sensitivity and/or function due to the high energetic requirements for fatty acid storage, adipokine secretion (160), insulin signaling (161), and glucose uptake.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [160]
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- Authors
- Koh, E. H., Park, J.-Y., Park, H.-S., Jeon, M. J., Ryu, J. W., Kim, M., Kim, S. Y., Kim, M.-S., Kim, S.-W., Park, I. S., Youn, J. H., & Lee, K.-U.
- Affiliations
- University of Ulsan (KR)
- Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea
- Inha University (KR)
- University of Southern California (US)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-12-01
- Volume
- 56
- Issue
- 12
- Pages
- 2973-2981
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2122444113
- Cited by
- 275
- References
- 45
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 17 · 2023: 17 · 2022: 14 · 2021: 12 · 2020: 23 · 2019: 18 · 2018: 10 · 2017: 17 · 2016: 12 · 2015: 15 · 2014: 16 · 2013: 18 · 2012: 20
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kanazawa University
- Korea Science and Engineering Foundation
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adiponectin, mitochondrial function, adipocytes, mitochondrial biogenesis, obesity, rosiglitazone, endoplasmic reticulum stress, JNK, ATF3, NRF1, db/db mice, adipose tissue, insulin sensitivity
- MeSH terms
- Rosiglitazone, Adipose Tissue, Animals, Diabetes Mellitus, Type 2, DNA, Mitochondrial, Endoplasmic Reticulum, Epididymis, Fatty Acids, Nonesterified, Gene Expression Regulation, Male, Mice, Obese, Mitochondria, Obesity, Oxygen Consumption, RNA, Messenger, Stress, Physiological, Adipocytes, Thiazolidinediones, Mice, Adiponectin
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