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

Author
item GOMEZ-ABELLAN, PURIFICACION - Universidad De Murcia
item GOMEZ-SANTOS, CECILIA - Universidad De Murcia
item MADRID, JUAN - Universidad De Murcia
item MILAGRO, FERMIN - University Of Navarra
item CAMPION, JAVIER - University Of Navarra
item MARTINEZ, J - University Of Navarra
item LUJAN, JUAN - University Hospital Virgen De La Arrixaca Of Murcia
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item GARAULET, MARTA - Universidad De Murcia

Submitted to: Nutricion Hospitalaria
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2011
Publication Date: 11/1/2011
Citation: Gomez-Abellan, P., Gomez-Santos, C., Madrid, J.A., Milagro, F.I., Campion, J., Martinez, J.A., Lujan, J.A., Ordovas, J.M., Garaulet, M. 2011. Site-specific circadian expression of leptin and its receptor in human adipose tissue. Nutricion Hospitalaria. 26(6):1394-1401.

Interpretive Summary: Leptin is a protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important hormones derived from fat cells. The variability of circulating leptin levels in relation to the body’s internal clock (circadian rhythm) has been well established over the last decade. However, the circadian behavior of leptin and its receptor in human body fat (adipose tissue – AT) remains unknown. Our goal was to investigate the circadian behavior of leptin and its receptor expression in biopsies of both the fat surrounding the organs (visceral adipose tissue- VAT) and fat located beneath the skin (subcutaneous adipose tissue SAT) obtained from six morbid obese women. AT samples were cultured over the course of 24-hours and gene expression was analyzed at the following times: 08:00, 14:00, 20:00 and 02:00 , using quantitative real-time PCR. Our results show that leptin expression showed a varied pattern that was consistent with circadian rhythm in cultured AT and similar patterns were noted for the leptin receptor. Leptin showed its maximum expression during the night, which might be associated to a lower degree of fat accumulation and higher mobilization. When comparing both fat deposits, VAT anticipated its expression towards afternoon and evening hours. In summary, we have demonstrated circadian rhythm 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 role of leptin in human AT.

Technical Abstract: Circadian variability of circulating leptin levels has been well established over the last decade. However, the circadian behavior of leptin in human adipose tissue remains unknown. This also applies to the soluble leptin receptor. We investigated the ex vivo circadian behavior 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 greater than or equal to 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. Leptin expression showed an oscillatory pattern that was consistent with circadian rhythm in cultured 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 mobilization. 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 association was lost when adjusting for waist circumference. Circadian rhythmicity has been demonstrated 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.