Reverse Feed Research Articles

Timing of Food Intake Drives the Circadian Rhythm of Blood Pressure.

Timing of food intake has become a critical factor in determining overall cardiometabolic health. We hypothesized that timing of food intake entrains circadian rhythms of blood pressure (BP) and renal excretion in mice. Male C57BL/6J mice were fed ad libitum or reverse feeding (RF) where food was available at all times of day or only available during the 12-h lights-on period, respectively. Mice eating ad libitum had a significantly higher mean arterial pressure (MAP) during lights-off compared to lights-on (113 ± 2 mmHg vs 100 ± 2 mmHg, respectively; P < 0.0001); however, RF for 6 days inverted the diurnal rhythm of MAP (99 ± 3 vs 110 ± 3 mmHg, respectively; P < 0.0001). In contrast to MAP, diurnal rhythms of urine volume and sodium excretion remained intact after RF. Male Bmal1 knockout mice (Bmal1KO) underwent the same feeding protocol. As previously reported, Bmal1KO mice did not exhibit a diurnal MAP rhythm during ad libitum feeding (95 ± 1 mmHg vs 92 ± 3 mmHg, lights-off vs lights-on; P > 0.05); however, RF induced a diurnal rhythm of MAP (79 ± 3 mmHg vs 95 ± 2 mmHg, lights-off vs lights-on phase; P < 0.01). Transgenic PERIOD2::LUCIFERASE knock-in mice were used to assess the rhythm of the clock protein PERIOD2 in ex vivo tissue cultures. The timing of the PER2::LUC rhythm in the renal cortex and suprachiasmatic nucleus was not affected by RF; however, RF induced significant phase shifts in the liver, renal inner medulla, and adrenal gland. In conclusion, the timing of food intake controls BP rhythms in mice independent of Bmal1, urine volume, or sodium excretion.

Timing of food intake differentially impacts urinary electrolyte and aldosterone excretion

The time‐of‐day variation in sodium excretion can be regulated by many different peptides and hormones, such as aldosterone. Numerous studies have shown that the circadian clock modulates the ability of aldosterone to regulate sodium balance, indicating a functional consequence of their interaction. Normally, renal sodium excretion has a distinct diurnal pattern, independent of time of intake, yet the interaction between the time of intake and the amount of salt ingested has yet to be determined. Our lab sought to determine what effect the timing of food intake has on the diurnal rhythm of renal electrolyte excretion, and whether or not this timing affects aldosterone as well. Male Sprague Dawley rats were implanted with telemetry devices to monitor mean arterial pressure (MAP). Following at least 7 days of recovery, rats were housed in metabolic cages and placed on a normal salt diet (0.49% NaCl). Following two days of baseline urine collections at 12‐hour intervals (Zeitgeber Time [ZT] 0 to ZT12 [lights on] or ZT12‐ZT24 [lights off]) under ad libitum feeding conditions, we restricted their access to food for 7 days to only their inactive period (ZT0‐ZT12). Rats were given free access to water during the reverse feeding (RF) conditions. As expected, rats allowed food ad libitum had a diurnal rhythm in sodium excretion as evidenced by a significantly higher sodium excretion during their active period (P&lt;0.05); active:inactive (A/I) sodium excretion was (2.82 ± 0.20). The rhythm in sodium excretion was not significantly different after 7 days of RF compared to ad libitum rats (2.03 ± 0.28 A/I, P=NS vs. ad libitum). As expected, potassium excretion was significantly greater during the active period in rats fed under ad libitum conditions (P&lt;0.05; A/I = 2.32 ± 0.16). Interestingly, RF significantly reduced the diurnal variation in urinary potassium excretion (0.89 ± 0.16, P&lt;.05 vs. ad libitum) as potassium excretion remained high during the inactive period. Although urinary aldosterone levels were similar in both ad libitum and RF conditions during the active period (89 ± 17 vs. 97 ± 18 pg/12 hr, P=NS), RF prevented the normal diurnal rhythm in aldosterone excretion resulting in significantly higher levels during the inactive period compared to ad libitum (138 ± 25 pg/12 hr vs. 25 ± 8, respectively, P&lt;0.05). There were no differences in 12‐hour MAP or activity between ad libitum and reverse feeding conditions. Our findings suggest that consuming food during the inactive phase impairs the diurnal variation in aldosterone production. In addition, the inappropriately high aldosterone excretion during the inactive period appears to be consistent with elevated potassium excretion during this period as well.Support or Funding InformationThis research was supported in part by the NHLBI Program Project grant HL136267, the NIH Career Development Award K99 HL127178, the NIGMS Pre‐doctoral Training Grant in Cell and Molecular Biology (CMB) T‐32 Training Grant T32GM008111‐30, and the UAB School of Medicine AMC21 Multi‐Investigator Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of Long Term Reverse Feeding on the Reproductive and Non-reproductive Tissues in Male Mice.

Previously, we demonstrated that the shift and/or restriction of feeding time during relatively short-term period (4 weeks) could alter the pituitary gonadotropin expression and the weights of seminal vesicle and prostate in rats. We also found that the reverse feeding (RF) schedule (up to 8 weeks) might induce an adaptable metabolic stress and cause impairment of androgen-dependent reproductive tissues. In the present study, we extended the RF time regimen up to 12 weeks, and measured the reproductive tissue weights. After 4 and 8 weeks of RF, the weights of epididymis were not significantly different. After 12 weeks, however, epididymis weights of RF animals were significantly different (CON 12W : RF 12W = 48.26±0.62 mg : 44.05±1.57 mg, p<0.05). After 4 and 12 weeks of feeding, seminal vesicle weights of RF animals were significantly decreased (CON 4W : RF 4W = 79.36±8.34 mg : 46.28±2.43 mg, p<0.001; CON 12W : RF 12W = 72.04±3.76 mg : 46.71±2.27 mg, p<0.001, respectively). Prostate weights were not changed by RF. Kidney and spleen weights of RF animals were significantly different on weeks 4 and 12 (Kidney, CON 4W : RF 4W = 249.72±4.20 mg : 228.41±3.03 mg, p<0.001; CON 12W : RF 12W = 309.15±7.49 mg : 250.72±6.13 mg, p<0.001, respectively, Spleen, CON 4W : RF 4W = 111.26±3.76 mg : 96.88±4.69 mg, p<0.05; CON 12W : RF 12W = 123.93±10.72 mg : 94.68±5.65 mg, p<0.05, respectively). Histology analysis of seminal vesicle revealed that the thinner epithelial cell layers, reduced complexities of swollen papilla folding in the exocrine glands on weeks 4 and 12 of RF. There was no histological difference between control and RF group on week 8. The present study indicates that up to 12 weeks RF induced differential changes in tissue weights of male mice. In particular, seminal vesicle, kidney and spleen seemed to temporarily adapted to the RF-induced metabolic stress on week 8 of feeding schedule. These results confirmed the our previous study that the RF might induce an adaptable metabolic stress and cause impairment of androgen-dependent reproductive tissues such as epididymis and seminal vesicle as well as non-reproductive tissues such as kidney and spleen. Further studies will be needed to achieve a better understanding of the how does mealtime shift affect the reproductive function and exact nature of adaptation.