Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation: Potential link with metabolic complications

Abstract

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.

Lipopolysaccharide binding protein is an adipokine involved in the resilience of the mouse adipocyte to inflammation

“…Adipocyte-secreted factors are known to be important in the modulation of a variety of processes, including energy balance, adipogenesis and systemic inflammation. Lipopolysaccharide (LPS) binding protein (LBP) is a well-known liver acute-phase reactant that has recently been identified as an adipokine [3,4]. The highest levels of LBP occur in fully differentiated human adipocytes from obese individuals [5].…”

A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction

“…However, despite the association of LBP concentration with changes in fat mass, all these studies claimed the liver as the main source of variation in the concentration of circulating LBP [14][15][16][17][18]. A recent study described LBP secretion by 3T3-L1 adipocytes [19] and increased serum LBP levels in genetically and diet-induced obese mice after LPS injection, but AT LBP production was not investigated [19]. Supporting this novel finding, Ge et al found Lbp gene expression and LBP protein secretion in 3T3-F442A cells and in de novo AT formed from 3T3-F442A cells, showing that its regulation was mediated by microRNA 883b (miR883b)-5p [20].…”

The possible role of antimicrobial proteins in obesity-associated immunologic alterations

“…These studies point out LBP as a causal candidate in the onset and progression of obesity-induced adipose tissue inflammation. Supporting this hypothesis, adipocyte LBP biosynthesis enhanced LPS-induced inflammatory response in macrophages [114]. Therefore, the proinflammatory effects of LBP [37] led us to suggest this protein as a strong candidate in the progression of adipocyte dysfunction.…”