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Extracellular conversion of adiponectin hexamers into trimers
Jeong-A Kim1, Martha Nuñez, David B Briggs
1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Bioscience Reports
|September 15, 2012
Summary
Adiponectin oligomers, specifically hexamers, can convert into trimers via an extracellular redox system. This conversion process, involving disulfide bond reduction, occurs outside the circulation and is enhanced by NADPH.
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Background:
- Adiponectin, an adipocyte-secreted hormone, circulates in various oligomeric forms including trimers, hexamers, and high-molecular-weight (HMW) species.
- The interconversion of these adiponectin forms, particularly the formation of trimers from larger oligomers outside the bloodstream, remains poorly understood.
Purpose of the Study:
- To investigate the potential for extracellular conversion of adiponectin hexamers and HMW forms into trimers.
- To elucidate the mechanisms underlying adiponectin oligomer interconversion, focusing on the role of extracellular redox systems.
Main Methods:
- Primary rat adipose cells and differentiated 3T3-L1 adipocytes were used to study adiponectin secretion and conversion.
- Purified adiponectin hexamers and HMW forms were incubated in conditioned media or within dialysis membranes in the presence of adipocytes.
- Experiments involved assessing N-terminal epitope-tagged hexamers, disulfide bond reduction, thiol-reactive agents, glutathione redox buffers, and NADPH/NADP+ effects.
Main Results:
- Adiponectin trimers were generated from larger oligomers secreted by both primary adipose cells and 3T3-L1 adipocytes.
- Purified hexamers, but not HMW adiponectin, converted into trimers in conditioned media and more efficiently within dialysis membranes near adipocytes.
- Evidence indicated a redox-mediated conversion, including tag integrity preservation, disulfide dimer-to-monomer conversion, inhibition by thiol-reactive agents, reductive conversion in glutathione buffer, and enhancement by NADPH.
Conclusions:
- Adiponectin hexamers can be converted into trimers through an extracellular redox system.
- This conversion mechanism is distinct from proteolytic processes and appears to involve reduction of disulfide bonds.
- The findings suggest the existence of an extracellular enzymatic or chemical system that regulates adiponectin oligomerization states.
