Adiponectin downregulates CD163 whose cellular and soluble forms are elevated in obesity.
BACKGROUND
CD163 is a monocyte/macrophage specific receptor whose soluble form (sCD163) is elevated in inflammatory diseases. Obesity is associated with chronic inflammation and low adiponectin, an anti-inflammatory adipokine. Adiponectin, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) and metformin activate the AMP-kinase that exerts anti-inflammatory effects, and the influence of adiponectin and these drugs on monocytic CD163 was analysed, and cellular and sCD163 were determined in obesity and type 2 diabetes.


METHODS
Monocytes were incubated with adiponectin, AICAR or metformin. Furthermore, monocytes and serum were obtained from type 2 diabetic patients (T2D), overweight (defined as a body mass index > or = 25 kg m(-2)) and normal-weight (NW) controls. CD163 was analysed by immunoblot and sCD163 was measured by enzyme-linked immunosorbent assay in the supernatants of the monocytes and in serum.


RESULTS
In monocytes, adiponectin reduced cellular and surface CD163, whereas sCD163 was not altered in the corresponding supernatants. Further, metformin and AICAR downregulated CD163. Monocytic CD163 was higher in T2D and obesity, whereas sCD163 in the supernatants was not elevated and neither correlated with serum sCD163 nor systemic adiponectin. There was a positive correlation of monocytic sCD163 with serum but not with monocytic IL-6. In the serum of obese controls and T2D patients, sCD163 was significantly higher compared to NW donors and was positively associated with systemic IL-6.


CONCLUSIONS
This study indicates that monocytic CD163 and systemic sCD163 are elevated in T2D and obesity. Adiponectin reduces CD163 in vitro, but additional factors related to obesity like IL-6 may be more relevant in vivo.
Sporrer
D
D
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Weber
M
M
Wanninger
J
J
Weigert
J
J
Neumeier
M
M
Stögbauer
F
F
Lieberer
E
E
Bala
M
M
Kopp
A
A
Schäffler
A
A
Buechler
C
C
D052242:Adiponectin / Q000008:administration & dosage* / Q000494:pharmacology; D000328:Adult; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects* / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics; D012265:Ribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D000098902:CD163 Antigen
D052242:Adiponectin; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D007004:Hypoglycemic Agents; D011956:Receptors, Cell Surface; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D008687:Metformin; C031143:AICA ribonucleotide