Complement factor H is expressed in adipose tissue in association with insulin resistance.
OBJECTIVE
Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance.


METHODS
Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts.


RESULTS
Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels.


CONCLUSIONS
Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances.
Moreno-Navarrete
José María
JM
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, and CIBER Fisiopatologia Obesidad y Nutricion, Instituto de Salud Carlos III, Girona, Spain.
Martínez-Barricarte
Rubén
R
Catalán
Victoria
V
Sabater
Mònica
M
Gómez-Ambrosi
Javier
J
Ortega
Francisco José
FJ
Ricart
Wifredo
W
Blüher
Mathias
M
Frühbeck
Gema
G
Rodríguez de Cordoba
Santiago
S
Fernández-Real
José Manuel
JM
D000273:Adipose Tissue / Q000502:physiology*; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D009852:Omentum; D009928:Organ Specificity; D012016:Reference Values; D000077154:Rosiglitazone; D012867:Skin; D045162:Thiazolidinediones / Q000627:therapeutic use; D015431:Weight Loss; D044465:White People / Q000235:genetics
C493495:CFH protein, human; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D017242:Complement Factor H; D011415:Complement Factor B