Food in synchrony with melatonin and corticosterone relieves constant light disturbed metabolism

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   Figure 1

   Constant light induces arrhythmicity in locomotor activity and hormonal levels. (A) Representative actograms that show daily locomotor activity monitored in rats under 12:12 light:darkness cycle (left) and exposed to constant light (right), both under ad libitum condition. A χ ² periodogram shows the absence of circadian rhythmicity under LL. (B) The levels of corticosterone and melatonin from LD ad libitum (LD-AL = black bars, n = 6) and LL ad libitum rats (LL-AL = white bars, n = 7) is shown. Data are presented as mean ± s.e.m. *Indicates statistical difference from ZT1 in LD-AL group (Student’s t test; P < 0.05) for corticosterone levels. *Statistical difference from ZT1 and ^†from ZT12 in LD-AL group (One-way ANOVA, Bonferroni’s post hoc test; P < 0.05) for melatonin levels.
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   Figure 2

   Metabolic disturbances caused by chronic constant light exposure. Metabolic profile of ad libitum under 12:12 LD cycle (LD-AL = black bars) and ad libitum under constant light (LL-AL = white bars) groups. (A) Hepatic TG content; (B) Serum TG; (C) β-hydroxybutyrate levels; (D) hepatic bile acids content; (E) White adipose tissue mass (eWAT = epididymal, rWAT = retroperitoneal and sWAT = subcutaneous) normalized with respect to body weight; (F) Blood glucose levels; (G) Serum insulin levels; (H) HOMA-IR (I) Glucose tolerance test (GTT) and (J) Area under the curve (AUC). Data are presented as mean ± s.e.m. (n = 6 for LD-AL and n = 7 for LL-AL). *Indicates statistical difference from LD-AL by Student-t test (P < 0.05) and Two-way ANOVA, (only for GTT assay, Tukey’s post hoc test, P < 0.05) respectively.
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   Figure 3

   Hormonal treatment recovers circadian locomotor activity and humoral rhythms. (A) Experimental design for the hormonal treatment. The apples and black line represent the time of hormone administration. Gray arrows represent the time points of blood sampling for hormonal determinations. (B) The actograms of LL + Veh (left) and LL + H (right). The apples represent the time of treatment (given after three weeks of LL) and their respective χ² periodogram is presented in the inferior part. (C) The levels of corticosterone and melatonin from vehicle (LL + Veh = white bars, n = 8) and treated (LL + H = dashed bars, n = 6) rats is shown. *Indicates statistical difference from ZT1 in LL + H group (Student’s t test; P < 0.05) for corticosterone levels. *Statistical difference from ZT1 and ^†from ZT12 in LL-H group (One-way ANOVA, Bonferroni post hoc test; P < 0.05) for melatonin levels.
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   Figure 4

   Hormonal treatment in LL ameliorated HS, hyperketonemia and hyperglycemia. Metabolic profile ad libitum under constant light plus vehicle (LL + Veh = white bars) and ad libitum under constant light plus hormonal treatment group (LL + H = dashed bars). (A) Hepatic TG content; (B) serum TG; (C) β-hydroxybutyrate levels; (D) hepatic bile acids content; (E) White adipose tissue mass (eWAT = epididymal, rWAT = retroperitoneal and sWAT = subcutaneous) normalized with respect to body weight; (F) Blood glucose levels; (G) Serum insulin levels; (H) HOMA-IR and (I and J) Glucose tolerance test (GTT) and the area under the curve (AUC). Data presented as mean ± s.e.m. (n = 8 LL-Veh and n = 6 LL + H). The horizontal stippled lines across histograms represent the LD-AL levels as reference. *Indicates statistical difference from LL + Veh group by Student-t test (P < 0.05) and Two-way ANOVA (only for GTT assay, Tukey’s post hoc test, P < 0.05) respectively.
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   Figure 5

   Scheduled restricted feeding improves glucose management homeostasis. Metabolic profile of control ad libitum fed (LD-AL = black bars) under LD cycle and restricted feeding in constant light rats (LL-RF = dark gray-pointed bars). (A) Hepatic TG content; (B) Serum TG; (C) Serum β-hydroxybutyrate levels (β-HB); (D) hepatic bile acids content; (E) White adipose tissue mass (eWAT = epididymal, rWAT = retroperitoneal and sWAT = subcutaneous) normalized with respect to body weight; (F) Blood glucose levels; (G) Serum insulin levels; (H) HOMA-IR and (I and J) Glucose tolerance test (GTT) and its respective area under the curve (AUC). Data are presented as mean ± s.e.m. (n = 6 for LD-AL and LL-RF). *Indicates statistical difference with LD-AL group (Student-t test, P < 0.05).
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   Figure 6

   Food in phase with hormonal treatment is a circadian reinforcement for locomotor activity. In (A) the protocol used for hormonal treatment in animals under restricted food (LL-RF) and hormonal treatment in phase (LL + H-RFi) and out of phase (LL + H-RFo) with respect to food access. (B) represents actograms for control (LL-RF) and experimental groups (LL + H, LL + H-RFi and LL + H-RFo) respectively. Gray shadows in the actogram represent the time of meal access. Only the animals receiving hormones in phase with food show a restored rhythm.
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   Figure 7

   Hormonal treatment in phase with food improves disturbed LL glucose metabolism. Hepatic (A) and Serum TG (B), β-hydroxybutyrate levels (C), hepatic bile acids (D), white adipose tissue mass (eWAT = epididymal, rWAT = retroperitoneal and sWAT = subcutaneous) normalized with respect to body weight (E), blood glucose levels (F), serum insulin levels (G); HOMA-IR (H) and glucose tolerance test (I and J) were determined in control LD-AL (black bars n = 6), LL restricted food access in phase with hormonal treatment (LL + H-RFi = light pointed bars) and LL restricted food access animals out of phase with respect to hormonal treatment (LL + H-RFo = black pointed bar) respectively. Data presented as mean ± s.e.m. (n = 6 LL-RF and n = 9 LL + H-RFi/LL + H-RFo). *Indicates statistical difference against LD-AL and ^†from LL+H-RFi group by One-way ANOVA (Bonferroni’s post hoc, P < 0.05) and Two-way ANOVA (only for GTT assay, Tukey’s post hoc test, P < 0.05) respectively.

• © 2017 Society for Endocrinology