The global increase in metabolic, cardiovascular, and neurological diseases is a major public health concern (Chew et al., 2023). These diseases have a multifactorial origin, and changes in lifestyle, nutrition, and environmental conditions are generally considered to be the main causes of their growing prevalence. Excessive fructose consumption, mainly from processed foods and sweetened beverages, is considered to be one of the risk factors (Taskinen et al., 2019). Fructose has a different mechanism of absorption and metabolism compared with glucose (Geidl-Flueck and Gerber, 2017), explaining its high lipogenic properties (Dekker et al., 2010). Numerous experimental studies indicate that high fructose intake is linked to increased body weight, hypertriglyceridaemia, hyperglycaemia, and insulin resistance (Toop and Gentili, 2016), although several other studies failed to prove these effects (Ackerman et al., 2005; Berenyiova et al., 2021).

Artificial light at night (ALAN) is another pervasive environmental risk factor that contributes to the recent increase in metabolic and neurological diseases (Burns et al., 2024; Windred et al., 2024). The global nighttime light emissions have been increasing since the second half of the twentieth century. Between 2011 and 2022, there was a 2 %–10 % increase in nighttime emissions per year (Linares Arroyo et al., 2024). The mechanisms by which ALAN can affect health are not sufficiently understood, but the disruption of circadian control of physiological and behavioural processes is frequently considered (Allada and Bass, 2021). The circadian system imposes a rhythmic pattern on physiology and behaviour via the central oscillator localised in the suprachiasmatic nuclei (SCN) of the hypothalamus and peripheral oscillators located throughout the body (Cox and Takahashi, 2019). Circadian rhythms are generated by a set of clock genes and their protein products, which form transcriptional/translational feedback loops generating approximately (circa) 24-h oscillations. The transcription factors CLOCK and BMAL1 stimulate the transcription of clock genes period (Per1, Per2, and Per3) and cryptochrome (Cry1 and Cry2), and their protein products repress the transcriptional activity of the CLOCK/BMAL1 dimer. During the day, Per and Cry transcription is high in the SCN and parallels its high electrical activity (Morris et al., 2012). The central clock is dominantly entrained by the light/dark (LD) cycle, while the peripheral oscillators, consisting of the same molecular components, are preferentially entrained by food-related signals, physical activity, and temperature (Yagita et al., 2001).

The SCN consists of subsets of gamma-aminobutyric acid (GABA)-ergic neurons, which co-express diverse neuropeptides, including arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) in the dorsomedial and ventrolateral part of the SCN, respectively (Wen et al., 2020). The AVP and VIP neurons project from the SCN to different hypothalamic and extrahypothalamic areas and impose rhythmic patterns on a plethora of physiological and behavioural processes, including reproduction, metabolism, basal temperature and their endocrine control (Buijs et al., 2021).

Disruption of the LD cycle by ALAN predominantly affects the central oscillator, as indicated by suppressed daily rhythmicity of the clock proteins PER1 and PER2 (Fonken et al., 2013) and the core clock genes Per1 and Per2 and the clock-output gene Nr1d1 (Rev-Erbα) (Okuliarova et al., 2022). Subsequently, the endocrine system is desynchronised (Okuliarova et al., 2022; Zeman et al., 2023), although only melatonin and corticosterone are usually studied (Rumanova et al., 2020). The pineal hormone melatonin has a special position in the research of light pollution because its rhythmic biosynthesis is directly controlled by the SCN, and it exhibits distinct circadian rhythmicity, with high levels during the dark time in both diurnal and nocturnal species (Arendt, 2019). High nocturnal concentrations are suppressed after exposure to ALAN in different animal species (Grubisic et al., 2019), with high interindividual variability, at least in humans (Phillips et al., 2019) and in a wider behavioural context (Helm et al., 2024). Moreover, melatonin receptors are highly expressed in the SCN, brain, and different organs, and thus can modulate central and peripheral oscillators and, subsequently, the neuroendocrine, cardiovascular, and immune systems (Dubocovich, 2007).

Exposure to ALAN and increased fructose intake may adversely affect the hormonal control of physiological processes, but their effects have been studied insufficiently and never in combination. Thus, the objective of this study was to investigate the potentially additive or synergistic effects of both risk factors on the central oscillator and its hormonal circadian outputs. To mimic real-life conditions more closely, we applied a 10 % fructose solution in the drinking water, which is analogous to the concentrations typically consumed in sugar-sweetened beverages (Toop and Gentili, 2016). We exposed animals to low-intensity ALAN (2 lux), which is common in urban environments, and evoked significant hormonal and metabolic alteration in our previous experiments (Okuliarova et al., 2020; Rumanova et al., 2022). We monitored the rhythmicity in the SCN via expression of the clock gene Per1, genes encoding expression the neuromodulators AVP and VIP, and genes encoding two glutamic acid decarboxylases (GAD65 and GAD67), which determine the bioavailability of the neurotransmitter GABA. In the hormonal analysis, we focussed on day/night differences in the concentrations of melatonin, adrenocorticotropic hormone (ACTH), corticosterone, testosterone, and thyroid hormones, which are under direct hypothalamic circadian control, and also quantified the major metabolic hormones leptin, adiponectin, and insulin. We tested the hypothesis that concurrent exposure to high fructose intake and ALAN weakens the robustness of the central circadian clock and modifies the production of circulating hormones. The results can elucidate the underlying mechanisms by which light pollution and high energy intake exert a detrimental effect on neuroendocrine control mechanisms.