Effects of 6‐meals‐a‐day feeding and 6‐meals‐a‐day feeding combined with adrenalectomy on daily gene expression rhythms in rat epididymal white adipose tissue

Abstract

The master clock in the hypothalamic suprachiasmatic nucleus (SCN) is assumed to synchronize the tissue-specific rhythms of the peripheral clocks with the environmental day/night changes via neural, humoral and/or behavioral connections. The feeding rhythm is considered an important Zeitgeber for peripheral clocks, as daytime feeding reverses (clock) gene rhythms in the periphery, but not in the SCN. In this study, we investigated the necessity of a daily feeding rhythm for maintaining gene expression rhythms in epididymal white adipose tissue (eWAT). We showed that 7 of 9 rhythmic metabolic/adipokine genes, but not clock genes, lost their rhythmicity upon exposure to 6-meals-a-day feeding. Previously, we showed comparable effects of adrenalectomy on eWAT; therefore, subsequently we investigated the effect of simultaneous disruption of these humoral and behavioral signaling pathways, by exposing adrenalectomized animals to 6-meals-a-day feeding. Interestingly, under these conditions, all the clock genes and 10 of 11 rhythmic metabolic/adipokine genes lost their rhythmicity. These data indicate that adrenal hormones and feeding rhythm are indispensable for maintaining daily rhythms in metabolic/adipokine gene, but not clock gene, expression in eWAT. In contrast, at least one of these two signals should be present in order for eWAT clock gene rhythms to be maintained.

The role of feeding rhythm, adrenal hormones and neuronal inputs in synchronizing daily clock gene rhythms in the liver

“…In the present study we showed that the daily rhythm of clock gene expression in the liver is still intact under 6-meals-a-day feeding conditions, after adrenalectomy, after total hepatic denervation or after total hepatic denervation with adrenalectomy or 6-meals-a-day feeding schedule. These results are similar to previous findings in liver (Cailotto et al 2005;Oishi et al 2005;Pezuk et al 2012;Sujino et al 2012), epididymal white adipose tissue (eWAT) (Su et al 2014(Su et al , 2015, kidney (Pezuk et al 2012;Sujino et al 2012), salivary gland (Pezuk et al 2012) and lung (Pezuk et al 2012). Together these findings demonstrate that feeding rhythm, adrenal hormones (in particular corticosterone) and neuronal inputs are not indispensable for synchronized daily clock gene rhythms.…”

“…We found that the daily rhythm of clock gene expression was lost after simultaneous disruption of the adrenal hormone and feeding rhythms, a result very much similar to what Ikeda et al (Ikeda et al 2014) found in mouse liver and kidney and what Su et al found in white adipose tissue (Su et al 2015). In their mice study Ikeda et al (Ikeda et al 2014) showed that 6M þ ADX treatment affected clock gene rhythms in the periphery without affecting the SCN clock.…”

“…It is well known that Visfatin/ NAMPT (Asher et al 2008;Grimaldi et al 2009;Imai et al 2000;Nakahata et al 2008Nakahata et al , 2009Ramsey et al 2009) can affect the daily Per2, Clock and Bmal1 rhythms. Recently we showed that 6M and 6M þ ADX abolished the daily rhythm of Visfatin/Nampt expression in eWAT (Su et al 2015). Thus 6M may reduce the Per1 amplitude via the Visfatin/NAMPT effect on clock genes.…”

“…In the kidney, eWAT and liver at least rhythmic feeding or adrenal hormones need to be present in order for clock gene rhythms to be maintained (Ikeda et al 2014;Su et al 2015). On the other hand, in the salivary gland sympathetic input is more important for the maintenance of clock gene rhythms than feeding rhythms and adrenal hormones (Ikeda et al 2014;Vujovic et al 2008).…”

Complex interaction between circadian rhythm and diet on bile acid homeostasis in male rats

“…factors that do not lose their daily rhythmicity in the 6M condition, such as corticosterone or melatonin (Su et al 2016b). Interestingly, Shp lost its rhythm in the 6M condition suggesting that Shp mRNA expression is more strongly driven by food intake than by the hepatic molecular clock.…”