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Title: Circadian expression of adiponectin and its receptors in human adipose tissue

Author
item GOMEZ-ABELLAN, PURIFICACION - Universidad De Murcia
item GOMEZ-SANTOS, CECELIA - Universidad De Murcia
item MADRID, JUAN ANTONIO - Universidad De Murcia
item MILAGRO, FERMIN - University Of Navarra
item CAMPION, JAVIER - University Of Navarra
item MARTINEZ, J. ALFREDO - University Of Navarra
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item GARAULET, MARTA - Universidad De Murcia

Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2009
Publication Date: 1/1/2010
Citation: Gomez-Abellan, P., Gomez-Santos, C., Madrid, J., Milagro, F.I., Campion, J., Martinez, J., Ordovas, J.M., Garaulet, M. 2010. Circadian expression of adiponectin and its receptors in human adipose tissue. Endocrinology. 151(1):115-122.

Interpretive Summary: Adiponectin is a hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism. Adiponectin is exclusively secreted from adipose tissue into the bloodstream and is very abundant in plasma relative to many hormones. Levels of the hormone are inversely correlated with body fat percentage in adults and it is one of the most clinically relevant hormones associated with obesity. The concentrations of many of the proteins in plasma change during the day following a circadian rhythm. The rhythmicity of adiponectin in human adipose tissue (AT) has not been analyzed. To assess whether the adiponectin and its receptors (ADIPOR1 and ADIPOR2) might show daily circadian rhythms in visceral and subcutaneous fat we investigated AT biopsies obtained from morbidly obese women using explants cultured during 24 h. Gene expression was analyzed at the following times: 0800, 1400, 2000, and 0200 h. All genes investigated showed a circadian rhythmicity. Adiponectin gene expression fluctuated in the same phase as its receptors. Correlation analyses between the genetic circadian oscillation and components of the metabolic syndrome revealed that adiposity and abdominal obesity correlated with a decrease in adiponectin and adiponectin receptors ADIPOR1 and ADIPOR2 amplitude. Moreover, the behavior of visceral and subcutaneous fat was different. Therefore, this work demonstrates for the first time in humans that Adiponectin and its receptors have 24-h rhythmicity and the behavior is different in visceral and subcutaneous fat. This is consistent with the different metabolic behavior observed in these fat depots.

Technical Abstract: Adiponectin is one of the most clinically relevant cytokines associated with obesity. However, circadian rhythmicity of adiponectin in human adipose tissue (AT) has not been analyzed. To assess whether the mRNA levels of adiponectin and its receptors (ADIPOR1 and ADIPOR2) might show daily circadian rhythms in visceral and sc fat explants obtained from morbid obese women, visceral and sc abdominal AT biopsies (n = 6) were obtained from morbidly obese women (body mass index >or=40 kg/m(2)). Anthropometric variables were measured and fasting plasma glucose, lipid, and lipoprotein concentrations were analyzed. To investigate rhythmic expression pattern, AT explants were cultured during 24 h, and gene expression was analyzed at the following times: 0800, 1400, 2000, and 0200 h, using quantitative real-time PCR. All genes investigated showed a circadian rhythmicity and oscillated accurately and independently of the suprachiasmatic nucleus in both AT explants (P < 0.05). Adiponectin gene expression fluctuated in the same phase as its receptors. Correlation analyses between the genetic circadian oscillation and components of the metabolic syndrome revealed that adiposity and abdominal obesity correlated with a decrease in adiponectin and adiponectin receptors ADIPOR1 and ADIPOR2 amplitude (P < 0.05). Visceral fat showed a trend toward a phase delay and dampening of the mRNA amplitude of adiponectin as compared with sc fat. The mRNA expression of adiponectin and its receptors showed 24-h rhythmicity in human AT from morbidly obese patients.