Role of insulin and free fatty acids in the regulation of ob gene expression and plasma leptin in normal rats.
OBJECTIVE
It is under debate whether free fatty acids (FFAs) play an independent role in the regulation of adipose cell functions. In this study, we evaluated whether leptin secretion induced by FFA is due directly to an increased FFA availability or whether it is mediated by insulin levels.


METHODS
To test this hypothesis, we compared the effects of six different experimental designs, with different FFA and insulin levels, on plasma leptin: euglycemic clamp, euglycemic clamp + FFA infusion, FFA infusion alone, FFA + somatostatin infusion, somatostatin infusion alone, and saline infusion.


RESULTS
Our results showed that euglycemic clamp, FFA infusion, or both in combination induced a similar increment of circulating leptin (3.31 +/- 0.30, 3.40 +/- 0.90, and 3.35 +/- 0.80 ng/mL, respectively). Moreover, the inhibition of FFA-induced insulin increase by means of somatostatin infusion completely abolished the rise of leptin in response to FFA (1.05 +/- 0.30 vs. 3.40 +/- 0.90 ng/mL, p < 0.001).


CONCLUSIONS
In conclusion, our data showed that the effects of high FFA levels on plasma leptin were mediated by the rise of insulin concentration. These data confirm a major role for insulin in the regulation of leptin secretion from rat adipose tissue and support the hypothesis that leptin secretion is coupled to net triglyceride synthesis in adipose tissue.
Pagano
Claudio
C
Endocrine Metabolic Library, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy. claudio.pagano@unipd.it
Dorigo
Alberto
A
Nisoli
Enzo
E
Tonello
Cristina
C
Calcagno
Alessandra
A
Tami
Valeria
V
Granzotto
Marnie
M
Carruba
Michele O
MO
Federspil
Giovanni
G
Vettor
Roberto
R
D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000008:administration & dosage
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D013004:Somatostatin