Responses of leptin to short-term fasting and refeeding in humans: a link with ketogenesis but not ketones themselves.
We investigated the response of leptin to short-term fasting and refeeding in humans. A mild decline in subcutaneous adipocyte ob gene mRNA and a marked fall in serum leptin were observed after 36 and 60 h of fasting. The dynamics of the leptin decline and rise were further substantiated in a 6-day study consisting of a 36-h baseline period, followed by 36-h fast, and a subsequent refeeding with normal diet. Leptin began a steady decline from the baseline values after 12 h of fasting, reaching a nadir at 36 h. The subsequent restoration of normal food intake was associated with a prompt leptin rise and a return to baseline values 24 h later. When responses of leptin to fasting and refeeding were compared with that of glucose, insulin, fatty acids, and ketones, a reverse relationship between leptin and beta-OH-butyrate was found. Consequently, we tested whether the reciprocal responses represented a causal relationship between leptin and beta-OH-butyrate. Small amounts of infused glucose equal to the estimated contribution of gluconeogenesis, which was sufficient to prevent rise in ketogenesis, also prevented a fall in leptin. The infusion of beta-OH-butyrate to produce hyperketonemia of the same magnitude as after a 36-h fast had no effect on leptin. The study indicates that one of the adaptive physiological responses to fasting is a fall in serum leptin. Although the mediator that brings about this effect remains unknown, it appears to be neither insulin nor ketones.
Kolaczynski
J W
JW
Division of Endocrinology and Metabolic Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Considine
R V
RV
Ohannesian
J
J
Marco
C
C
Opentanova
I
I
Nyce
M R
MR
Myint
M
M
Caro
J F
JF
D020155:3-Hydroxybutyric Acid; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology; D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000378:metabolism*; D020738:Leptin; D008297:Male; D009765:Obesity; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007657:Ketone Bodies; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D020155:3-Hydroxybutyric Acid