Pinealectomy interferes with the circadian clock genes expression in white adipose tissue

Abstract

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24-hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev-erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP-citrate lyase, malic enzyme, fatty acid synthase, and glucose-6-phosphate dehydrogenase) was abolished in pinealectomized animals.

Inter‐relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity

“…Several research groups have investigated the potential inter‐relationships between adiponectin and melatonin (Tables and ). It was found that pinealectomy did not change the adiponectin mRNA levels in the epididymal AT of rats . A high‐fructose diet in rats resulted in a decrease in circulating adiponectin.…”

“…Thus, the periodic exposure of adipocytes to melatonin synchronized their metabolic and hormonal functions in a circadian fashion, mimicking the daily light–dark cycle observed in animals. It was shown in another study that the daily pattern of the expression of Clock, Per2, and Cry1 clock genes was abolished in the epididymal AT of pinealectomized rats . Pinealectomy also affected the expression of Ppar γ and Rev‐erb α , the nuclear receptors involved in the circadian expression of the clock‐controlled genes.…”

“…Pinealectomy also affected the expression of Ppar γ and Rev‐erb α , the nuclear receptors involved in the circadian expression of the clock‐controlled genes. These changes in the biological clock rhythm in WAT may be involved in the negative effects of obesity and metabolic syndrome . Interestingly, a high‐fat diet was found to cause significant changes in the 24‐hr pattern of clock gene expression in the anterior pituitary of rats and decreases in the amplitude of nocturnal melatonin levels .…”

Melatonin multiple effects on brown adipose tissue molecular machinery

“…Melatonin has been shown to regulate BAT, acting as a recruiter and increasing its thermogenic capacity . Despite its regulatory role in other metabolic active tissues and the evidences of its interaction with BAT, little is known about its role in the metabolic thermogenic pathway either in its daily regulation or after acute challenges. The present work aimed to analyze that using pinealectomized and melatonin‐treated pinealectomized animals.…”

Melatonin Supplementation Lowers Oxidative Stress and Regulates Adipokines in Obese Patients on a Calorie‐Restricted Diet

“…Many metabolic processes in adipose tissue, including the expression and secretion of some adipokines, are under circadian control [24, 25]. This regulation may be at least partly mediated by melatonin, which could have actions on WAT by means of its membrane receptors or via an action on the sympathetic nervous system [26, 27]. …”