Soluble CD163 correlates with lipid metabolic adaptations in type 1 diabetes patients during ketoacidosis

Abstract

Introduction: Diabetic ketoacidosis (DKA) is associated with inflammation and increased lipolysis. The macrophage activation marker, soluble CD163 (sCD163), is associated with obesity, non-alcoholic fatty liver disease and type 2 diabetes. We aimed to investigate whether sCD163 correlates with key elements of lipolysis in type 1 diabetes patients during mild DKA. Materials and Methods: We investigated nine patients with type 1 diabetes twice during: (i) euglycemic control conditions and a bolus of saline; and (ii) hyperglycemic ketotic conditions induced by lipopolysaccharide administration combined with insulin deprivation. Blood samples, indirect calorimetry, palmitate tracer and adipose tissue biopsies were used to investigate lipid metabolism. Results: We observed a significant increase in plasma sCD163 levels after lipopolysaccharide exposure (P < 0.001). Concentrations of sCD163 were positively correlated with plasma concentrations of free fatty acids, palmitate rate of appearance and lipid oxidation rates, and negatively correlated to the expression of G0/G1 switch 2 gene messenger ribonucleic acid content in adipose tissue (P < 0.01 for all). Furthermore, sCD163 levels correlated positively with plasma peak concentrations of cortisol, glucagon, tumor necrosis factor-a, interleukin-6 and interleukin-10 (P < 0.01 for all). Data on lipolysis and inflammation have previously been published. Conclusions: Macrophage activation assessed by sCD163 might play an important role in DKA, as it correlates strongly with important components of lipid metabolism including free fatty acids, palmitate, lipid oxidation, G0/G1 switch 2 gene and pro-inflammatory cytokines during initial steps of DKA. These results are novel and add important knowledge to the field of DKA.

Soluble CD163-Associated Dietary Patterns and the Risk of Metabolic Syndrome

“…In agreement with previous studies [1,2], the current study found that sCD163 independently predicted central obesity, MetS, and NAFLD. In addition, the finding of the study further strengthened the importance of a healthy dietary pattern in preventing diet-related chronic disease such as elevated sCD163 levels and MetS.…”

“…Substantial evidence has demonstrated a positive relationship between circulating soluble cluster of differentiation 163 (sCD163) concentrations and obesity-related comorbidities such as diabetes, non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS) [1,2]. CD163 is a transmembrane scavenger receptor mainly expressed on monocyte-macrophage cell lineages.…”

Targeting of CD163+ Macrophages in Inflammatory and Malignant Diseases

“…sCD163 is a marker of macrophage activation [ 65 ] and it has been associated with a number of inflammatory diseases such as atherosclerosis [ 80 , 81 ], hemophagocytic lymphohistiocytosis [ 82 , 83 , 84 ] and diabetes mellitus [ 85 , 86 ] including diabetic polyneuropathy [ 87 ], diabetic ketoacidosis [ 88 ] and proliferative diabetic retinopathy [ 89 , 90 ]. Further, a recent paper reviewed sCD163 as a potential biomarker of acute and chronic liver disease and found it elevated in relation to severity in multiple studies [ 91 ].…”

Macrophage Activation Markers, Soluble CD163 and Mannose Receptor, in Liver Fibrosis

“…CD163, a hemoglobin-haptoglobin scavenger receptor, is exclusively expressed by monocytes and macrophages ( 23 , 24 ) and exerts its main biological function through elimination of hemoglobin-haptoglobin complexes during hemolysis ( 25 ). A soluble form (sCD163) is present in the plasma ( 26 ), and enzymatic receptor cleavage of CD163 by the TACE/ADAM17 system is highly upregulated in response to inflammatory stimuli, including the PAMP lipopolysaccharide (LPS) ( 27 – 30 ). The mannose receptor is primarily expressed by macrophages, dendritic cells and endothelial cells ( 31 ) and is involved in scavenging events including endogenous molecule clearance besides antigen presentation ( 32 ).…”