Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery.

Objective.Obesity is associated with metabolic dysfunction with sex differences and chronic, low-grade inflammation.We proposed that hepatic expression of immune complement C3 related receptors (C3aR, C5aR, and C5L2) would be associated with preor postmenopausal status and metabolic profile in severely obese women. We hypothesized that C5L2/C5aR ratio, potentially influencing the ASP/C5L2 metabolic versus C5a/C5aR immune response, would predictmetabolic profiles after weight loss surgery. Materials and Methods. Fasting plasma (hormone, lipid, and enzyme analysis) and liver biopsies (RT-PCR gene expression) were obtained from 91 women during surgery. Results. Hepatic C5L2 mRNA expression was elevated in pre- versus postmenopausal women ( P< 0.01) and correlated positively with circulating estradiol, estrone, ApoB, ApoA1, ApoA1/B, waist circumference, age, and LDL-C (all P < 0.05).While plasma ASP was lower in pre- versus postmenopausal women (P < 0.01), the hepatic C5L2/C5aR mRNA ratio was increased (P < 0.001) and correlated positively with estrone (P < 0.01) and estradiol (P < 0.001) and negatively with circulating ApoB and liver enzymes ALT, AST, and GGT (all P < 0.05). Over 12 months postoperatively, liver enzymes in low C5L2/C5aR mRNA ratio group remained higher (ALP and ALT, P < 0.05, AST and GGT, P < 0.001 2-way-ANOVA). Conclusion. C5L2-C5aR association with othermediators including estrogens may contribute to hepatic metabolic and inflammatory function. [ABSTRACT FROM AUTHOR]