Site-specific circadian expression of leptin and its receptor in human adipose tissue

Introduction: Circadian variability of circulating lep- tin levels has been well established over the last decade. However, the circadian behavior of leptin in human adi- pose tissue remains unknown. This also applies to the sol- uble leptin receptor. Objective: We investigated the ex vivo circadian behav- ior of leptin and its receptor expression in human adipose tissue (AT). Subjects and methods: Visceral and subcutaneous abdominal AT biopsies (n = 6) were obtained from morbid obese women (BMI 40 kg/m 2 ). Anthropometric variables and fasting plasma glucose, leptin, lipids and lipoprotein concentrations were determined. In order to investigate rhythmic expression pattern of leptin and its receptor, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h, using quantitative real-time PCR. Results: Leptin expression showed an oscillatory pat- tern that was consistent with circadian rhythm in cul- tured AT. Similar patterns were noted for the leptin receptor. Leptin showed its achrophase (maximum expression) during the night, which might be associated to a lower degree of fat accumulation and higher mobi- lization. When comparing both fat depots, visceral AT anticipated its expression towards afternoon and evening hours. Interestingly, leptin plasma values were associated with decreased amplitude of LEP rhythm. This associa- tion was lost when adjusting for waist circumference. Conclusion: Circadian rhythmicity has been demon- strated in leptin and its receptor in human AT cultures in a site-specific manner. This new knowledge paves the way for a better understanding of the autocrine/paracrine role of leptin in human AT.