Increased leptin production in vivo and insulin cleavage by the omental adipose tissue of morbidly obese patients.
OBJECTIVE
The aim of this investigation was to assess the insulin cleavage capacity in obese humans. Increased insulin degradation by visceral adipose tissue has previously been demonstrated in obese rats and could be interpreted as a physiological response to hyperinsulinaemia. The recent characterization of leptin receptors in pancreatic beta cells, liver and muscle suggests that leptin may influence insulin function and metabolism. Our study focuses on the possible relationship between leptin secretion and adipose tissue insulin-degrading capacity.


METHODS
Insulin and leptin were measured in arterial blood and in the epiploic vein of morbidly obese (n = 7) and non-obese patients (n = 7) who were undergoing abdominal surgery. Arteriovenous insulin difference (AV insulin) was considered an in vivo marker of insulin degradation by the omental fat tissue. Statistical comparison between venous and arterial leptin was used to assess endogenous leptin production.


METHODS
Insulin was measured using an oligoclonal IRMA and leptin levels were determined by using a specific radioimmunoassay.


RESULTS
Morbidly obese patients were hyperinsulinaemic compared to non-obese patients according to arterial insulin levels (P = 0.049) but not to venous levels. Insulin cleavage capacity, nil in the control group, was clearly significant in the morbidly obese patients (P = 0.001). In the morbidly obese group, leptin levels in venous epiploic samples were significantly higher (P = 0.028) than in the arterial samples, confirming in situ the synthesis of leptin by human white adipose tissue. We also observed a correlation between insulin arterial levels and venous leptin concentrations (P = 0.009) which supports the chronic leptinogenic effect of insulin suggested in previous works. Finally, our results show that venous leptin levels are correlated with the extent of insulin cleavage by omental tissue (P = 0.033).


CONCLUSIONS
Morbidly obese patients have a higher white adipose tissue insulin cleavage capacity, which could partially diminish hyperinsulinaemia-derived adverse effects. High leptin production, a consequence of high insulin levels, may act as a signal to the insulin-degrading tissues in order to lower insulinaemia.
Cuatrecasas
G
G
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Spain.
Granada
M L
ML
Formiguera
X
X
Rull
M
M
Alastrué
A
A
Remesar
X
X
Alemany
M
M
Foz
M
M
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D015592:Immunoradiometric Assay; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D020738:Leptin; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism*; D009852:Omentum; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D011863:Radioimmunoassay
D007328:Insulin; D020738:Leptin; D011506:Proteins