Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation: potential link with metabolic complications.
Chronic low-grade infection has been suggested to be associated with metabolic disorder such as diabetes. However, the molecular mechanism underlying this important association is largely unknown. The only clue established so far is that many subjects exhibit elevated levels of C-reactive protein as measured by highly sensitive assay. Here, we hypothesized that adipocyte-macrophage interaction plays a key role in amplifying such low grade infection to the level of influencing metabolic disorders. The presence of macrophages in abdominal adipose tissues was investigated by immunohistochemistry. To see whether molecules associated with acute phase protein, LPS signaling, and persistent recruitment of monocytes, are produced at higher amounts in adipocytes co-cultured with macrophages stimulated with low concentration of LPS (1 ng/ml), we measured serum amyloid A (SAA), LPS binding protein (LBP), soluble CD14 (sCD14), and RANTES levels in culture supernatant of co-cultures. Lastly, we investigated in vivo effect of low-grade LPS infusion on the production of these molecules using obese model mice. The macrophages were certainly identified in abdominal adipose tissues. Investigated molecules, especially LBP, SAA, and RANTES were produced at higher amounts in co-cultures stimulated with LPS compared with the cells without LPS. The ob/ob, and high-fat diet-induced obesity mice produced higher amounts of LBP, SAA, and RANTES one day after LPS infusion (1 ng/ml/g body weight) compared with ob/- and normal-fat fed control mice. Thus, adipocytes and infiltrated macrophages, and their interaction with low endotoxin stimulation appear to play an important role in amplifying and maintaining LPS-induced low-grade inflammation.
Department of Dental Science for Health Promotion, Hiroshima University Graduate School of Biomedical Science, Minami-ku, Hiroshima, Japan.
Hideo
H
Nakarai
Akiko
A
Yamashita
Shintaro
S
Nagayasu
Misaki
M
Iwashita
Sonoko
S
Kumamoto
Hideki
H
Ohyama
Masaki
M
Hata
Yoshihiko
Y
Soga
Akifumi
A
Kushiyama
Tomoichiro
T
Asano
Yoshimitsu
Y
Abiko
Fusanori
F
Nishimura
D050153:Abdominal Fat / Q000473:pathology; D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020738:Leptin / Q000235:genetics; D052439:Lipid Metabolism Disorders / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018946:Chemokine CCL5; D020738:Leptin; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000685:Serum Amyloid A Protein; D000099231:Lipopolysaccharide-Binding Protein