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. 2021 Oct 29;65(5):549-561.
doi: 10.20945/2359-3997000000407. Epub 2021 Sep 29.

Restricted feeding modulates peripheral clocks and nutrient sensing pathways in rats

Luis Guilherme F Rodrigues  1 , Leonardo D de Araujo  2 , Silvia L R Roa  1 , Ana C Bueno  3 , Ernane T Uchoa  2 , José Antunes-Rodrigues  2 , Ayrton C Moreira  1 , Lucila L K Elias  2 , Margaret de Castro  1 , Clarissa S Martins  4
Affiliations

Restricted feeding modulates peripheral clocks and nutrient sensing pathways in rats

Luis Guilherme F Rodrigues et al. Arch Endocrinol Metab. .

Abstract

Objective: Feeding restriction in rats alters the oscillators in suprachiasmatic, paraventricular, and arcuate nuclei, hypothalamic areas involved in food intake. In the present study, using the same animals and experimental protocol, we aimed to analyze if food restriction could reset clock genes (Clock, Bmal1) and genes involved in lipid metabolism (Pgc1a, Pparg, Ucp2) through nutrient-sensing pathways (Sirt1, Ampk, Nampt) in peripheral tissues.

Methods: Rats were grouped according to food access: Control group (CG, food ad libitum), Restricted night-fed (RF-n, food access during 2 h at night), Restricted day-fed (RF-d, food access during 2 h in the daytime), and Day-fed (DF, food access during 12 h in the daytime). After 21 days, rats were decapitated at ZT3 (0900-1000 h), ZT11 (1700-1800 h), or ZT17 (2300-2400 h). Blood, liver, brown (BAT) and peri-epididymal (PAT) adipose tissues were collected. Plasma corticosterone and gene expression were evaluated by radioimmunoassay and qPCR, respectively.

Results: In the liver, the expression pattern of Clock and Bmal1 shifted when food access was dissociated from rat nocturnal activity; this phenomenon was attenuated in adipose tissues. Daytime feeding also inverted the profile of energy-sensing and lipid metabolism-related genes in the liver, whereas calorie restriction induced a pre-feeding increased expression of these genes. In adipose tissues, Sirt1 expression was modified by daytime feeding and calorie restriction, with concomitant expression of Pgc1a, Pparg, and Ucp2 but not Ampk and Nampt.

Conclusion: Feeding restriction reset clock genes and genes involved in lipid metabolism through nutrient-sensing-related genes in rat liver, brown, and peri-epididymal adipose tissues.

Keywords: Caloric restriction; biological clocks; circadian rhythm; feeding behavior; sirtuin 1.

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Conflict of interest statement

Disclosure: no potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1. Schematic design of the experiment.
Figure 2
Figure 2. Clock and Bmal1 gene expression (2-ΔΔCt) in the liver, BAT (brown adipose tissue), and PAT (peri-epididymal adipose tissue) of Control group (CG), Day-fed (DF), Restricted night-fed (RF-n), and Restricted day-fed (RF-d) rats at ZT3 (0900 h), ZT11 (1700 h), and ZT17 (2300 h).
Figure 3
Figure 3. Relative expression (2-ΔΔCt) of energy-sensing genes ( Sirt1 , Ampk , and Nampt ) and lipid metabolism-related genes ( Pparg , Pgc1a , and Ucp2 ) in the liver, BAT (brown adipose tissue), and PAT (peri-epididymal adipose tissue) of Control group (CG), Day-fed (DF), Restricted night-fed (RF-n), and Restricted day-fed (RF-d) rats at ZT3 (0900 h), ZT11 (1700 h), and ZT17 (2300 h).
Figure 4
Figure 4. Schematic summary of study hypothesis and main results. Food restriction, in dissociation with rat nocturnal activity, alters the expression pattern of clock genes in peripheral tissues, such as liver and adipose tissues. These interactions may occur through Sirt1 , a nutrient-sensing gene. BAT: brown adipose tissue; PAT: peri-epididymal adipose tissue; SCN: suprachiasmatic nucleus.
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