Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum

Abstract

Aims/hypothesis Adiponectin is an adipocyte-derived secretory factor that is specifically produced in adipocytes. It exerts effects on energy homeostasis via peripheral and central mechanisms. However, it is not clear whether adiponectin crosses the blood-brain barrier in humans. In serum, adiponectin circulates in several different complexes, each of which has distinct functions. Here, we wanted to test whether adiponectin can be found in human cerebrospinal fluid (CSF) and whether specific adiponectin complexes are enriched in CSF compared with peripheral serum samples. We also wanted to establish whether there is a sex-related difference with regard to the distribution of adiponectin oligomers in CSF. Materials and methods We studied 22 subjects (11 men, 11 women) in this study. Their average BMI was 28.0± 4.7 kg/m 2 ; average age was 70±7 years. Results Analysis of total adiponectin revealed that adiponectin protein is present in human CSF at approximately 0.1% of serum concentration. The distribution of adiponectin oligomers differs considerably in CSF from that of serum within matched samples from the same patients. Only the adiponectin trimeric and low-molecular-mass hexameric complexes are found in CSF, with a bias towards the trimeric form in most patients. Male subjects have a higher CSF: serum ratio of total adiponectin (p<0.05; n=20) and have slightly higher trimer levels in serum and CSF than female subjects. Conclusions/interpretation We conclude that the adiponectin trimer is the predominant oligomer in human CSF.

The impact of obesity on secretion of adiponectin multimeric isoforms differs in visceral and subcutaneous adipose tissue

“…Due to large molecular size of adiponectin, especially the HMW form, there is limitation in transport across the blood-brain barrier. 34 Similar limitation could be expected at the level of AT endothelial barrier; however, no evidence of a differential transendothelial transport of adiponectin multimers has been revealed. Adiponectin profile might also be influenced beyond AT endothelium level.…”

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

“…Recent studies suggest that different multimeric forms of adiponectin can influence its ability to pass the blood-brain barrier and its biological activity (14)(15)(16)(17). Next, we examined the effects of social-defeat stress on the distribution of oligomeric complexes of adiponectin using gel filtration chromatography followed by immunoblotting.…”

“…(D) Body weight and body composition measured by DEXA at the end of the experiments. CSD has no significant effect on body weight (t (14) = 1.438 P = 0.172), fat mass (t (14) = 0.5138, P = 0.615) or lean mass (t (14) = 0.5682, P = 0.579). n = 8 per group.…”

“…Full-length adiponectin is the predominant circulating form and can be found as a trimer, hexamer, or high molecular weight (HMW) oligomer (10,12), whereas globular adiponectin exists as a trimer (13). Evidence shows that adiponectin enters the brain from circulation (14)(15)(16)(17). Intraventricular (i.v.)…”

Adiponectin: mechanistic insights and clinical implications

“…How relevant are the actions in the brain? Adiponectin can easily be detected in cerebrospinal fluid [69], and has potent central effects pharmacologically to decrease body weight and increase energy expenditure [70,71]. Much still remains to be investigated in this area.…”