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

Abstract

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 pre- or 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 predict metabolic 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 other mediators including estrogens may contribute to hepatic metabolic and inflammatory function.

Immunological Processes Driving IgE Sensitisation and Disease Development in Males and Females

“…In addition, TLR4 expression in macrophages also appears to be dependent on estrogen, and elevated estrogen levels increase TLR4 expression [ 111 ]. Complement proteins and complement receptors are also under the influence of sex hormones in some tissues such as the liver, where the majority of complement proteins are produced [ 112 , 113 , 114 ]. Whether this also holds true in the airways and if this further relates to clinical outcomes remains to be elucidated.…”

The Controversial C5a Receptor C5aR2: Its Role in Health and Disease

“…C5a-C5aR1 and ASP-C5aR2 signals acted in concert to regulate immune and metabolic responses in adipose tissue [ 120 ]. The association of C5aR2/C5aR1 with metabolic processes was also found in obese women with age-matched controls as well as obese women pre- and postbariatric surgery [ 121 , 122 ].…”

The Importance of C5aR2 in Neutrophil Function and Its Impact on Neutrophil-mediated Diseases

“…Of note, based on its intracellular localization, C5aR2 may also contribute to immunometabolism, i.e., the impact of immune functions on cell metabolism [16,34,49,50].…”