Leucine in food mediates some of the postprandial rise in plasma leptin concentrations.
In vitro, leptin secretion is regulated at the level of mRNA translation by the rapamycin-sensitive mammalian target of rapamycin (mTOR) and its agonist leucine (Leu). Studies were conducted on meal-trained rats to evaluate the potential physiological relevance of these in vitro findings and the role of Leu in affecting rises in plasma leptin observed after a meal. In the first study, we correlated changes in plasma insulin and Leu to mTOR-signaling pathway activation and plasma leptin at different times during meal feeding. Rapid rises in plasma insulin and Leu, along with mTOR signaling (phosphorylation of eIF4G, S6K1, rpS6, and 4E-BP1) in adipose tissue were observed during the 3-h meal and declined thereafter. Plasma leptin rose more slowly, peaking at 3 h, and was inhibited by rapamycin (0.75 mg/kg) pretreatment. In another experiment, oral Leu or norleucine was provided instead of a meal. Leu and norleucine stimulated a rise in plasma leptin; however, the magnitude was less than the response to a complete meal. In a third study, rats were provided a meal that lacked Leu, branched-chain amino acids, or all amino acids. Stimulation of leptin secretion was reduced approximately 40% in animals provided the Leu-deficient meal. Further reductions were not observed by removing the other amino acids. Thus Leu appears to regulate most of the effects of dietary amino acids on the postprandial rise in plasma leptin but is responsible only for part of the leptin response to meal feeding.
Lynch
Christopher J
CJ
Dept. of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. clynch@psu.edu
Gern
Beth
B
Lloyd
Carolyn
C
Hutson
Susan M
SM
Eicher
Rachel
R
Vary
Thomas C
TC
D000284:Administration, Oral; D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004435:Eating / Q000502:physiology; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D007328:Insulin / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000097:blood*; D007930:Leucine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009646:Norleucine / Q000008:administration & dosage / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D039603:Eukaryotic Initiation Factor-4G; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D010750:Phosphoproteins; D038601:Ribosomal Protein S6; D014280:Triglycerides; D009646:Norleucine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512963:Rps6ka1 protein, rat; D007930:Leucine; D000409:Alanine; D020123:Sirolimus