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01.10.2006 | Article

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin

verfasst von: J. M. Fernández-Real, M. Straczkowski, J. Vendrell, F. Soriguer, S. Pérez del Pulgar, L. Gallart, A. López-Bermejo, I. Kowalska, M. Manco, F. Cardona, M. M. García-Gil, G. Mingrone, C. Richart, W. Ricart, A. Zorzano

Erschienen in: Diabetologia | Ausgabe 10/2006

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Abstract

Aims/hypothesis

Decreased sensing of the innate immune system may lead to chronic activation of the inflammatory cascade. We hypothesised that mannan-binding lectin (MBL) deficiency may confer risk of obesity and insulin resistance.

Materials and methods

We performed a cross-sectional study of MBL protein concentration (n=434) and MBL2 gene mutations (exon 1) (n=759) in association with obesity, markers of inflammation and insulin action (euglycaemic clamp, n=113), and a longitudinal study of MBL protein before and after weight loss in obese patients (n=10). We also studied the effects of MBL in vitro in muscle cells and circulating MBL-A (mouse equivalent of human MBL) in a mouse model.

Results

Among 434 consecutive non-diabetic men, the age-adjusted serum MBL concentration was lower in obese subjects than in lean subjects (median: 959 μg/ml [interquartile range: 116.8–2,044 μg/ml] vs 1,365 [467–2,513] μg/ml; p=0.01) and was accompanied by increased serum inflammatory markers. Insulin action correlated significantly with serum MBL (r=0.49, p<0.0001). Serum MBL concentration increased by a median of 110.2% after weight loss. The change in serum concentration of MBL was positively associated with the increase in insulin sensitivity (r=0.713, p=0.021). At least one MBL2 gene mutation was present in 48.2% of obese vs 39.3% of non-obese subjects (p=0.037). The plasma concentration of MBL-A was lower in insulin-resistant obese ob/ob mice, as was the glucose/insulin ratio. Incubation of rat soleus muscle with human MBL markedly increased fatty acid oxidation.

Conclusions/interpretation

These findings suggest that MBL, previously thought only to be involved in inflammation and immune system function, affects metabolic pathways.

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Titel: Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin
verfasst von: J. M. Fernández-Real
M. Straczkowski
J. Vendrell
F. Soriguer
S. Pérez del Pulgar
L. Gallart
A. López-Bermejo
I. Kowalska
M. Manco
F. Cardona
M. M. García-Gil
G. Mingrone
C. Richart
W. Ricart
A. Zorzano
Publikationsdatum: 01.10.2006
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 10/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0381-6

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