Article

Diabetologia

, Volume 48, Issue 3, pp 519-528

Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition

  • C. PoitouAffiliated withDepartment of Nutrition and Biochemistry, French Institute of Health and Medical Research Avenir, EA 3502, Paris VI University, Hôtel-Dieu Hospital
  • , N. ViguerieAffiliated withObesity Research Unit of the French Institute of Health and Medical Research, U586, Louis Bugnard Institute, Paul Sabatier University
  • , R. CancelloAffiliated withDepartment of Nutrition and Biochemistry, French Institute of Health and Medical Research Avenir, EA 3502, Paris VI University, Hôtel-Dieu Hospital
  • , R. De MatteisAffiliated withInstitute of Normal Human Morphology–Anatomy, University of Ancona
  • , S. CintiAffiliated withInstitute of Normal Human Morphology–Anatomy, University of Ancona
  • , V. StichAffiliated withDepartment of Sports Medicine and Obesity Unit, Charles University
  • , C. CoussieuAffiliated withDepartment of Nutrition and Biochemistry, French Institute of Health and Medical Research Avenir, EA 3502, Paris VI University, Hôtel-Dieu Hospital
  • , E. GauthierAffiliated withCytopathology and Nephrology Departments, Georges Pompidou European Hospital
  • , M. CourtineAffiliated withDepartment of Nutrition and Biochemistry, French Institute of Health and Medical Research Avenir, EA 3502, Paris VI University, Hôtel-Dieu HospitalLIM/BIO, North Paris University
    • , J. D. ZuckerAffiliated withDepartment of Nutrition and Biochemistry, French Institute of Health and Medical Research Avenir, EA 3502, Paris VI University, Hôtel-Dieu HospitalLIM/BIO, North Paris University
    • , G. S. BarshAffiliated withDepartment of Pediatrics and Genetics, Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine
    • , W. SarisAffiliated withDepartment of Human Biology Nutrition Research Institute Maastricht, Maastricht University
    • , P. BrunevalAffiliated withCytopathology and Nephrology Departments, Georges Pompidou European Hospital
    • , A. BasdevantAffiliated withDepartment of Nutrition and Biochemistry, French Institute of Health and Medical Research Avenir, EA 3502, Paris VI University, Hôtel-Dieu Hospital
    • , D. LanginAffiliated withObesity Research Unit of the French Institute of Health and Medical Research, U586, Louis Bugnard Institute, Paul Sabatier University
    • , K. ClémentAffiliated withDepartment of Nutrition and Biochemistry, French Institute of Health and Medical Research Avenir, EA 3502, Paris VI University, Hôtel-Dieu HospitalDepartment of Nutrition, Hôtel Dieu Email author 

Abstract

Aims/hypothesis

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.

Results

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.

Conclusions/interpretation

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.

Keywords

Adipocyte Amyloidosis Calorie restriction Gene expression profiling Leptin receptor Obesity Serum amyloid A Stroma vascular fraction Very-low-calorie diet