The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals.
OBJECTIVE
Little is known of the metabolism of different isoforms of adiponectin. We therefore (a) characterised the size distribution of human adiponectin in relation to gender, body composition and following a challenge with a fat meal or oral glucose in humans, and (b) studied the metabolism of isoforms of human adiponectin in rabbits.


METHODS
Electrophoresis, blotting and chromatography were used to characterise human adiponectin in 36 healthy subjects, including 15 with at least two first-degree relatives with type 2 diabetes, before and after consumption of a fatty meal or glucose. The metabolism of column-fractionated human adiponectin was studied in rabbits, some of which were coinjected with insulin.


RESULTS
Females had a higher proportion of high molecular weight (HMW) and hexameric adiponectin (P = 0.002 and 0.004 respectively), and a lower proportion of trimers (P < 0.0001) than males. Females also showed a strong negative relationship between body fat measures and the proportion of HMW adiponectin. There were no differences in isoforms between insulin-resistant and -sensitive subjects, or following oral glucose or a fat meal. Adiponectin in rabbits had an extravascular/intravascular ratio of 0.71, and a half-life (T1/2) of 14.3 h. Metabolism was not influenced by insulin or reduction of sulphydryl bonds. HMW and trimeric isoforms had a significantly different T1/2 of 13.0 and 17.5 h respectively (P < 0.05), and these isoforms did not interconvert in vivo.


CONCLUSIONS
Human adiponectin is present as trimers, hexamers and HMW forms. Females had a higher proportion and absolute amount of HMW species compared with males, and female, but not male, subjects showed a strong negative relationship between measures of body fat, and the proportion of HMW species. These isoforms did not respond to challenge in man with a fatty meal or oral glucose, and in the rabbit, to injected insulin. HMW adiponectin was more rapidly metabolised than the trimeric form, but both were stable in vivo, and did not interconvert. We conclude that human adiponectin is much longer-lived than is the case with other hormones, a finding with positive implications for the potential to supplement levels of adiponectin in man.
Peake
Philip W
PW
Division of Medicine, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia. P.Peake@unsw.edu.au
Kriketos
Adamandia D
AD
Campbell
Lesley V
LV
Shen
Yvonne
Y
Charlesworth
John A
JA
D052242:Adiponectin; D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002845:Chromatography; D004041:Dietary Fats / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D020033:Protein Isoforms; D011817:Rabbits; D012737:Sex Factors
D052242:Adiponectin; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms