Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition
The acute-phase proteins, serum amyloid As (SAA), are precursors of amyloid A, involved in the pathogenesis of AA amyloidosis. This work started with the characterisation of systemic AA amyloidosis concurrent with SAA overexpression in the subcutaneous white adipose tissue (sWAT) of an obese patient with a leptin receptor deficiency. In the present study a series of histopathological, cellular and gene expression studies was performed to assess the importance of SAA in common obesity and its possible production by mature adipocytes.
Materials and methods
Gene expression profiling was performed in the sWAT of two extremely obese patients with a leptin receptor deficiency. Levels of the mRNAs of the different SAA isoforms were quantified in sWAT cellular fractions from lean subjects and from obese subjects before and after a very-low-calorie diet. These values were subsequently compared with serum levels of SAA in these individuals. In addition, histopathological analyses of sWAT were performed in lean and obese subjects.
In sWAT, the expression of SAA is more than 20-fold higher in mature adipocytes than in the cells of the stroma vascular fraction (p<0.01). Levels of SAA mRNA expression and circulating levels of the protein are sixfold (p<0.001) and 3.5-fold (p<0.01) higher in obese subjects than in lean subjects, respectively. In lean subjects, 5% of adipocytes are immunoreactive for SAA, whereas the corresponding value is greater than 20% in obese subjects. Caloric restriction results in decreases of 45–75% in levels of the transcripts for the SAA isoforms and in circulating levels of the protein.
The results of the present study indicate that SAA is expressed by sWAT, and its production at this site is regulated by nutritional status. If amyloidosis is seen in the context of obesity, it is possible that production of SAA by adipocytes could be a contributory factor.
- Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition
Volume 48, Issue 3 , pp 519-528
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- Calorie restriction
- Gene expression profiling
- Leptin receptor
- Serum amyloid A
- Stroma vascular fraction
- Very-low-calorie diet
- Industry Sectors
- Author Affiliations
- 1. Department of Nutrition and Biochemistry, French Institute of Health and Medical Research Avenir, EA 3502, Paris VI University, Hôtel-Dieu Hospital, Paris, France
- 2. Obesity Research Unit of the French Institute of Health and Medical Research, U586, Louis Bugnard Institute, Paul Sabatier University, Toulouse, France
- 3. Institute of Normal Human Morphology–Anatomy, University of Ancona, Ancona, Italy
- 4. Department of Sports Medicine and Obesity Unit, Charles University, Prague, Czech Republic
- 5. Cytopathology and Nephrology Departments, Georges Pompidou European Hospital, Paris, France
- 6. LIM/BIO, North Paris University, Paris, France
- 7. Department of Pediatrics and Genetics, Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, Standford, CA, USA
- 8. Department of Human Biology Nutrition Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
- 9. Department of Nutrition, Hôtel Dieu, place du parvis Notre-Dame, 75004, Paris, France