bims-ciryme 2019-11-03 papers

Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Oct 29. pii: S1388-1981(19)30184-2. [Epub ahead of print] 158533

Circadian profiling reveals distinct regulation of endocannabinoid system in the rat plasma, liver and adrenal glands by light-dark and feeding cycles.

Martin Sládek, Pavel Houdek, Alena Sumová.

Circadian clocks coordinate physiological and behavioral rhythms that allow the organism to anticipate and adapt to daily changes in environment. The clock-driven cellular oscillations are highly tissue specific to efficiently fine-tune local signaling, manage energy use and segregate incompatible processes. In most peripheral tissues, food acts as the main cue that entrains the oscillations to external time. Food intake and energy balance are under control of endocannabinoid (EC) signaling. Despite this obvious link between the circadian and EC systems, evidence for their interaction started to emerge only recently. We used targeted lipidomics to analyze circadian variations in EC tone in rat plasma, liver and adrenal tissue. The results provide the evidence that ECs, monoacylglycerols, N-acylethanolamines and their precursors oscillate with a tissue-specific circadian phase in plasma and liver. We then identified a set of rhythmically expressed genes likely responsible for the variations in EC tissue tone. In contrast to the liver, EC levels did not oscillate in the adrenal glands. Instead, we revealed that local EC receptor genes are under circadian regulation. To explore the impact of metabolic signals on expression of these genes, we used daytime-restricted feeding schedule. We subsequently showed that daytime feeding strongly suppressed liver-expressed fatty acid binding protein 5 (Fabp5) and adrenal-expressed non-canonical endocannabinoid receptors Gpr55 and Trpv1, whereas it upregulated liver-expressed Trpv1 and glycerophosphodiester phosphodiesterase 1 (Gde1). Our results reveal tissue-specific mechanisms involved in interaction between endocannabinoid signaling, circadian system and metabolism.

Keywords: Adrenal gland; Cannabinoid receptors; Circadian clock; Endocannabinoids; Rat liver; Restricted feeding

DOI: https://doi.org/10.1016/j.bbalip.2019.158533

J Biol Rhythms. 2019 Oct 31. 748730419883043

Reference Gene Optimization for Circadian Gene Expression Analysis in Human Adipose Tissue.

Jeremy M White, Matthew J Piron, Vittobai R Rangaraj, Erin C Hanlon, Ronald N Cohen, Matthew J Brady.

A hallmark of biology is the cyclical nature of organismal physiology driven by networks of biological, including circadian, rhythms. Unsurprisingly, disruptions of the circadian rhythms through sleep curtailment or shift work have been connected through numerous studies to positive associations with obesity, insulin resistance, and diabetes. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) measures oscillation in messenger RNA expression, an essential foundation for the study of the physiological circadian regulatory network. Primarily, measured oscillations have involved the use of reference gene normalization. However, the validation and identification of suitable reference genes is a significant challenge across different biological systems. This study focuses on adipose tissue of premenopausal, otherwise healthy, morbidly obese women voluntarily enrolled after being scheduled for laparoscopic sleeve gastrectomy surgery. Acquisition of tissue was accomplished by aspiratory needle biopsies of subcutaneous adipose tissue 1 to 2 weeks prior to surgery and 12 to 13 weeks following surgery and an in-surgery scalpel-assisted excision of mesenteric adipose tissue. Each biopsy was sterile cultured ex vivo and serially collected every 4 h over approximately 36 h. The candidate reference genes that were tested were 18S rRNA, GAPDH, HPRT1, RPII, RPL13α, and YWHAZ. Three analytic tools were used to test suitability, and the candidate reference genes were used to measure oscillation in expression of a known circadian clock element (Dbp). No gene was deemed suitable as an individual reference gene control, which indicated that the optimal reference gene set was the geometrically averaged 3-gene panel composed of YWHAZ, RPL13α, and GAPDH. These methods can be employed to identify optimal reference genes in other systems.

Keywords: circadian; human adipose tissue; qRT-PCR; reference gene; sleeve gastrectomy; weight loss surgery

DOI: https://doi.org/10.1177/0748730419883043

Cells. 2019 Oct 29. pii: E1342. [Epub ahead of print]8(11):

Feeding Entrainment of the Zebrafish Circadian Clock Is Regulated by the Glucocorticoid Receptor.

Elisa Morbiato, Elena Frigato, Alberto Dinarello, Francesca Maradonna, Nicola Facchinello, Francesco Argenton, Oliana Carnevali, Luisa Dalla Valle, Cristiano Bertolucci.

Glucocorticoids (GCs) are steroid hormones mainly acting as key regulators of body homeostasis and stress responses. Their activities are primarily based on the binding to the GC receptor (GR), a member of the nuclear receptor family, that regulates tissue-specific sets of genes. GCs secretion follows a circadian rhythmicity with a peak linked to the animal's activity phase. In mammals, GCs are also implicated in feeding entrainment mechanisms as internal zeitgeber. Here, we investigated, by means of behavioural and molecular approaches, the circadian clock and its regulation by light and food in wild-type (WT) and null glucocorticoid receptor (gr-/-) zebrafish larvae, juveniles and adults. In both WT and gr-/- larvae and adults, behavioural activity and clock gene expression were entrained to the light-dark (LD) cycle and rhythmic in constant conditions. Differences in the pattern of clock genes' expression indicated a modulatory role of GCs. A significant role of Gr was detected in the feeding entrainment which was absent or markedly dampened in mutants. Furthermore, the expression of two clock-regulated genes involved in glucidic and lipidic metabolism was altered, highlighting the participation of GCs in metabolic processes also in fish. Taken together, our results confirmed the role of GC-mediated Gr signaling in the feeding entrainment in a non-mammalian species, the zebrafish.

Keywords: Danio rerio; circadian clock; clock gene; entrainment; feeding; glucocorticoid receptors; metabolism; zebrafish

DOI: https://doi.org/10.3390/cells8111342