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)

Nutritional signals strongly regulate neuroendocrine axes, such as those su bserving release of LH, GH, and TSH, presumptively in part via the adipocyt e-derived neuroactive peptide leptin. In turn, leptin release is controlled by both acute (fasting) and long-term (adipose store) nutrient status. Her e, we investigate the neuroendocrine impact of short-term (2.5-day) fasting on leptin release in healthy young women studied in the steroid-replete mi dluteal 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 fast ing vs. fed session in separate menstrual cycles. Pulsatile leptin release was quantified by model-free Cluster analysis, the orderliness of leptin pa tterns by the approximate entropy statistic, and nyctohemeral leptin rhythm icity 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 mu g/L (P = 0.0007). Cluster analysis identified 13.9 +/- 1.1 and 14.3 +/- 1.1 lepti n peaks per 24 h in the fed and fasting states (P = NS), and unchanging lep tin interpeak intervals (89 +/- 5.4 vs. 92 +/- 5.3 min). Leptin peak area d eclined by 4.2-fold (155 +/- 21 us. 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 mu g/L, P = 0.001.1). 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 releas e patterns in fasting. Cross-correlation analysis revealed both positive (f ed) and negative (fasting) leptin-GH relationships, but no leptin-LH correl ations. In summary, short-term (2.5-day) fasting profoundly suppresses 24-h serum l eptin concentrations and pulsatile leptin release in the sex steroid-suffic ient midluteal phase of healthy women via mechanisms that selectively atten uate leptin pulse area and incremental amplitude. In contrast, the pulse-ge nerating, nyctohemeral phase-determining, and entropy-control mechanisms th at govern 24-h leptin release are not altered by acute nutrient restriction at this menstrual phase. Leptin-GH (but not leptin-LH) showed nutrient-dep endent positive (fed) and negative (fasting) cross-correlations. Whether si milar neuroendocrine mechanisms supervise altered leptin signaling during s hort-term nutrient restriction in men, children, or postmenopausal women is not known.