title: Short-term fasting selectively suppresses leptin pulse mass and 24-hour rhythmic leptin release in healthy midluteal phase women without disturbing leptin pulse frequency or its entropy control (pattern orderliness).
abstract: Nutritional signals strongly regulate neuroendocrine axes, such as those subserving release of LH, GH, and TSH, presumptively in part via the adipocyte-derived neuroactive peptide leptin. In turn, leptin release is controlled by both acute (fasting) and long-term (adipose store) nutrient status. Here, we investigate the neuroendocrine impact of short-term (2.5-day) fasting on leptin release in healthy young women studied in the steroid-replete midluteal phase of the normal menstrual cycle. Eight women each underwent 24-h blood sampling at 10-min intervals during a randomly ordered 2.5-day fasting vs. fed session in separate menstrual cycles. Pulsatile leptin release was quantified by model-free Cluster analysis, the orderliness of leptin patterns by the approximate entropy statistic, and nyctohemeral leptin rhythmicity by cosinor analysis. Mean (24-h) serum leptin concentrations fell by 4.6-fold during fasting; namely, from 15.2+/-2.3 to 3.4+/-0.6 microg/L (P = 0.0007). Cluster analysis identified 13.9+/-1.1 and 14.3+/-1.1 leptin peaks per 24 h in the fed and fasting states (P = NS), and unchanging leptin interpeak intervals (89+/-5.4 vs. 92+/-5.3 min). Leptin peak area declined by 4.2-fold (155+/-21 vs. 37+/-7 area units, P = 0.004), due to a reduction in incremental leptin pulse amplitude (4.4+/-0.7 vs. 1.0+/-0.13 microg/L, P = 0.0011). The cosine amplitude and mesor (mean) of the 24-h leptin rhythm decreased by 4-fold, whereas the acrophase (timing of the nyctohemeral leptin peak) remained fixed. The approximate entropy of leptin release was stable, thus indicating preserved orderliness of leptin release patterns in fasting. Cross-correlation analysis revealed both positive (fed) and negative (fasting) leptin-GH relationships, but no leptin-LH correlations. In summary, short-term (2.5-day) fasting profoundly suppresses 24-h serum leptin concentrations and pulsatile leptin release in the sex steroid-sufficient midluteal phase of healthy women via mechanisms that selectively attenuate leptin pulse area and incremental amplitude. In contrast, the pulse-generating, nyctohemeral phase-determining, and entropy-control mechanisms that govern 24-h leptin release are not altered by acute nutrient restriction at this menstrual phase. Leptin-GH (but not leptin-LH) showed nutrient-dependent positive (fed) and negative (fasting) cross-correlations. Whether similar neuroendocrine mechanisms supervise altered leptin signaling during short-term nutrient restriction in men, children, or postmenopausal women is not known.
authors.affiliation: Department of Pediatrics, University of Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Bergendahl
authors.forename: A
authors.initials: A
authors.lastname: Iranmanesh
authors.forename: W S
authors.initials: WS
authors.lastname: Evans
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D000328:Adult; D000465:Algorithms; D002940:Circadian Rhythm / Q000502:physiology; D016000:Cluster Analysis; D019277:Entropy; D005215:Fasting / Q000097:blood*; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D020738:Leptin / Q000097:blood*; D008183:Luteal Phase / Q000097:blood*
chemical_list: D006728:Hormones; D020738:Leptin