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Open access

Nikolaj Rittig, Mads Svart, Niels Jessen, Niels Møller, Holger J Møller and Henning Grønbæk


Macrophage activation determined by levels of soluble sCD163 is associated with obesity, insulin resistance, diabetes mellitus type 2 (DM2) and non-alcoholic fatty liver disease (NAFLD). This suggests that macrophage activation is involved in the pathogenesis of conditions is characterised by adaptions in the lipid metabolism. Since sCD163 is shed to serum by inflammatory signals including lipopolysaccharides (LPS, endotoxin), we investigated sCD163 and correlations with lipid metabolism following LPS exposure.


Eight healthy male subjects were investigated on two separate occasions: (i) following an LPS exposure and (ii) following saline exposure. Each study day consisted of a four-hour non-insulin-stimulated period followed by a two-hour hyperinsulinemic euglycemic clamp period. A 3H-palmitate tracer was used to calculate the rate of appearance (Rapalmitate). Blood samples were consecutively obtained throughout each study day. Abdominal subcutaneous adipose tissue was obtained for western blotting.


We observed a significant two-fold increase in plasma sCD163 levels following LPS exposure (P < 0.001), and sCD163 concentrations correlated positively with the plasma concentration of free fatty acids, Rapalmitate, lipid oxidation rates and phosphorylation of the hormone-sensitive lipase at serine 660 in adipose tissue (P < 0.05, all). Furthermore, sCD163 concentrations correlated positively with plasma concentrations of cortisol, glucagon, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 (P < 0.05, all).


We observed a strong correlation between sCD163 and stimulation of lipolysis and fat oxidation following LPS exposure. These findings support preexisting theory that inflammation and macrophage activation play a significant role in lipid metabolic adaptions under conditions such as obesity, DM2 and NAFLD.

Open access

Ermina Bach, Niels Møller, Jens Otto L Jørgensen, Mads Buhl and Holger Jon Møller


The macrophage-specific glycoprotein sCD163 has emerged as a biomarker of low-grade inflammation in the metabolic syndrome and related disorders. High sCD163 levels are seen in acute sepsis as a result of direct lipopolysaccharide-mediated shedding of the protein from macrophage surfaces including Kupffer cells. The aim of this study was to investigate if low-grade endotoxinemia in human subjects results in increasing levels of sCD163 in a cortisol-dependent manner.


We studied eight male hypopituitary patients and eight age- and gender-matched healthy controls during intravenous low-dose LPS or placebo infusion administered continuously over 360 min. Furthermore, we studied eight healthy volunteers with bilateral femoral vein and artery catheters during a 360-min infusion with saline and low-dose LPS in each leg respectively.


Systemic low-grade endotoxinemia resulted in a gradual increase in sCD163 from 1.65 ± 0.51 mg/L (placebo) to 1.92 ± 0.46 mg/L (LPS) at 220 min, P = 0.005 and from 1.66 ± 0.42 mg/L (placebo) to 2.19 ± 0.56 mg/L (LPS) at 340 min, P = 0.006. A very similar response was observed in hypopituitary patients: from 1.59 ± 0.53 mg/L (placebo) to 1.83 ± 0.45 mg/L (LPS) at 220 min, P = 0.021 and from 1.52 ± 0.53 mg/L (placebo) to 2.03 ± 0.44 mg/L (LPS) at 340 min, P < 0.001. As opposed to systemic treatment, continuous femoral artery infusion did not result in increased sCD163.


Systemic low-grade endotoxinemia resulted in increased sCD163 to levels seen in the metabolic syndrome in both controls and hypopituitary patients. This suggests a direct and cortisol-independent effect of LPS on the shedding of sCD163. We observed no effect of local endotoxinemia on levels of serum sCD163.

Open access

Esben Thyssen Vestergaard, Morten B Krag, Morten M Poulsen, Steen B Pedersen, Niels Moller, Jens Otto Lunde Jorgensen and Niels Jessen


Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.

Materials and methods

To study GH-independent effects of ghrelin, seven hypopituitary men undergoing replacement therapy with GH and hydrocortisone were given ghrelin (5 pmol/kg per min) and saline infusions for 300 min in a randomized, double-blind, placebo-controlled, crossover design. Circulating RBP4 levels were measured at baseline and during a hyperinsulinemic–euglycemic clamp on both study days. To study the direct effects of GH, nine healthy men were treated with GH (2 mg at 2200 h) and placebo for 8 days in a randomized, double-blind, placebo-controlled, crossover study. Serum RBP4 levels were measured before and after treatment, and insulin sensitivity was measured by the hyperinsulinemic–euglycemic clamp technique.


Ghrelin acutely decreased peripheral insulin sensitivity. Serum RBP4 concentrations decreased in response to insulin infusion during the saline experiment (mg/l): 43.2±4.3 (baseline) vs 40.4±4.2 (clamp), P<0.001, but this effect was abrogated during ghrelin infusion (mg/l): 42.4±4.5 (baseline) vs 42.9±4.7 (clamp), P=0.73. In healthy subjects, serum RBP4 levels were not affected by GH administration (mg/l): 41.7±4.1 (GH) vs 43.8±4.6 (saline), P=0.09, although GH induced insulin resistance.


i) Serum RBP4 concentrations decrease in response to hyperinsulinemia, ii) ghrelin abrogates the inhibitory effect of insulin on circulating RBP4 concentrations, and iii) ghrelin as well as GH acutely induces insulin resistance in skeletal muscle without significant changes in circulating RBP4 levels.

Open access

Esben S Lauritzen, Nikolaj Rittig, Ermina Bach, Niels Møller and Mette Bjerre


During the inflammatory acute phase response, plasma glucose and serum triglycerides are increased in humans. Fibroblast growth factor (FGF) 21 has plasma glucose and lipid-reducing actions, but its role in the acute inflammatory response in human is unknown.


To investigate circulating levels of FGF21 after lipopolysaccharide (LPS) infusion.


Two randomized, single-blinded, placebo-controlled crossover trials were used.


The studies were performed at a university hospital clinical research center.

Patients and interventions

Study 1 (LPS bolus): Eight young, healthy, lean males were investigated two times: (1) after isotonic saline injection and (2) after LPS injection (bolus of 1 ng/kg). Each study day lasted 4 h. Study 2 (continuous LPS infusion): Eight, healthy males were investigated two times: (1) during continuously isotonic saline infusion and (2) during continuous LPS infusion (0.06 ng/kg/h). Each study day lasted 4 h. Circulating FGF21 levels were quantified every second hour by an immunoassay.


A LPS bolus resulted in a late suppression (t = 240 min) of serum FGF21 (P = 0.035). Continuous LPS infusion revealed no significant effects on FGF21 levels (P = 0.82).


Our studies show that a bolus of LPS results in decreased FGF21 levels 4 h from exposure.