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Surfactant Protein D of the Innate Immune Defence is Inversely Associated with Human Obesity and SP‐D Deficiency Infers Increased Body Weight in Mice

Surfactant protein D (SP‐D) is a key regulator of pathogen‐induced inflammation. SP‐D is further involved in lipid homeostasis in mouse lung and circulation and recent data have demonstrated that the body mass index (BMI; in kg/m2) is influenced by genes in common with SP‐D. The objective of the present study was to describe the association between serum SP‐D and weight, waist circumference or BMI, and furthermore to observe body weight development in SP‐D‐deficient (Spd−/−) mice. As a part of the Danish population‐based twin study (GEMINAKAR) on the metabolic syndrome, we analysed 1476 Danish twins for serum SP‐D and investigated associations with weight, waist circumference and BMI by multiple regression analysis. Serum SP‐D was significantly and inversely associated with weight (P = 0.001) and waist circumference in men (P < 0.001) and to BMI in both genders (P = 0.039 women, P < 0.001 men). The age‐dependent increase in serum SP‐D was most prominent in lean persons (BMI < 20). Spd−/− mice and wild‐type mice were subjected to a feeding study and body weights were recorded in a time course over 24 weeks. Spd−/− mouse weight gain was significantly increased, with 90 mg/week (P < 0.0001) in males on normal chow. Fat percentage was significantly increased by 17% in the Spd−/− male mice (P = 0.003). We conclude, that there is an association between low levels or absent SP‐D and obesity.