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

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 microg/ml [interquartile range: 116.8-2,044 microg/ml] vs 1,365 [467-2,513] microg/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.

• Authors: 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
• Journal: Diabetologia (Diabetologia) Vol. 49 Issue 10 Pg. 2402-11 (Oct 2006) ISSN: 0012-186X [Print] Germany
• PMID: 16955210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Insulin
• Mannose-Binding Lectin
• DNA

Topics

• Adult
• Animals
• Blood Glucose (metabolism)
• Body Size
• Cardiovascular Diseases (epidemiology, prevention & control)
• DNA (blood, genetics, isolation & purification)
• Female
• Humans
• Inflammation (genetics, prevention & control)
• Insulin (blood)
• Insulin Resistance (physiology)
• Male
• Mannose-Binding Lectin (blood, genetics)
• Mice
• Mice, Obese
• Mutation