Serotonin, a possible intermediate between disturbed circadian rhythms and metabolic disease

Versteeg, Ruth I.; Serlie, Mireille J.; Kalsbeek, Andries; Fleur, Susanne E. la

doi:10.1016/j.neuroscience.2015.05.067

Cited by 45 publications

(34 citation statements)

References 174 publications

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“…Loss of MOD-1 caused complete suppression of satiety-induced quiescence in ets-5 mutant animals, suggesting that when animals are sated, modification of serotoninergic signaling can still regulate quiescence. The significance of this finding in C. elegans is unclear; nonetheless, there appears to be a conserved role for 5-HT in the regulation of feeding behavior in other systems (48).…”

Section: Discussionmentioning

confidence: 94%

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Juozaityte

Pladevall‐Morera

Podolska

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Animal behavior is shaped through interplay among genes, the environment, and previous experience. As in mammals, satiety signals induce quiescence in Caenorhabditis elegans. Here we report that the C. elegans transcription factor ETS-5, an ortholog of mammalian FEV/Pet1, controls satiety-induced quiescence. Nutritional status has a major influence on C. elegans behavior. When foraging, food availability controls behavioral state switching between active (roaming) and sedentary (dwelling) states; however, when provided with high-quality food, C. elegans become sated and enter quiescence. We show that ETS-5 acts to promote roaming and inhibit quiescence by setting the internal "satiety quotient" through fat regulation. Acting from the ASG and BAG sensory neurons, we show that ETS-5 functions in a complex network with serotonergic and neuropeptide signaling pathways to control food-regulated behavioral state switching. Taken together, our results identify a neuronal mechanism for controlling intestinal fat stores and organismal behavioral states in C. elegans, and establish a paradigm for the elucidation of obesity-relevant mechanisms.ETS transcription factor | neuronal signaling | satiety | fat levels | quiescence A nimal behavior is strongly influenced by the availability of food. In invertebrates and vertebrates, appetite, locomotor activity, and sleep rhythms are all driven by nutritional state (1-7). When malnourished, animals seek out a new food source by actively exploring their environment (roaming), whereas animals that are well fed tend to explore less (dwelling) and when fully sated enter a quiescent or sleep-like state (1-3, 8, 9). Transitions between these behavioral states can be regulated by sensory perception of external stimuli and through gut signals or other internal cues that are generated according to food quality (3,4,6).Initial evidence for neuronal regulation of feeding behavior was shown in mammals using hypothalamic lesions (10). Sectioning of specific regions within the rat hypothalamus evoked opposing behaviors. Removal of one section caused overeating and obesity, whereas removal of an adjacent section resulted in starvation owing to reduced eating (10). Subsequent studies showed that the pro-opiomelanocortin-expressing neurons in the hypothalamus function to suppress feeding, whereas a hypothalamic region that contains neuropeptide Y/agouti-related protein-expressing neurons promotes feeding (11). These adjacent brain regions integrate signals received from the gut that report satiety (12). The nutritive content of food itself also serves as a potent regulator of behavior. In mammals, a diet loaded with fats and sugars stimulates overfeeding and leads to obesity (13). In addition, rats can learn to select a source of food based exclusively on its nutritional value in the absence of external cues (14).In Caenorhabditis elegans, as in mammals, nutritive value is a behavioral stimulus (1, 4). Nematodes exhibit different behaviors when cultured on low-quality food compared to high-quality...

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Section: Discussionmentioning

confidence: 94%

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Juozaityte

Pladevall‐Morera

Podolska

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The circadian rhythm, in turn, controls the fluctuations of our physiological and behavioral activities within the period of 24 hours, which is extremely adjusted by self-regulated expression of the called CLOCK genes. Circadian rhythmicity is essential for the control of energy metabolism, cycle-wake, hormone production and cognitive performance (Versteeg, Serlie, Kalsbeek, & Fleur, 2015;Wang, et al 2016;Zouabi et al 2016). The circadian rhythm is regulated by various brain regions, particularly mediated through 5-HT, which can be evidenced by the large number of 5-HT receptors such as the types 1A, 1B, 2A, 2C, 5A and 7 subtypes in SCN (Smith et al 2015).…”

Section: Introductionmentioning

confidence: 99%

“…In this context, 5-HT is an important regulator of circadian rhythm, by modulating responses to photic and non-photic zeitgebers (Smith et al 2015;Versteeg, Serlie, Kalsbeek, & Fleur, 2015). As with the serotonergic system of the brain, deregulation of the circadian system is associated with a range of disturbance of behavior and development, including depression, bipolar disorder, autism and disorders of the sleep-wake cycle Cho et al 2016;Schaufler et al 2016).…”

Section: Introductionmentioning

confidence: 99%

“…As with the serotonergic system of the brain, deregulation of the circadian system is associated with a range of disturbance of behavior and development, including depression, bipolar disorder, autism and disorders of the sleep-wake cycle Cho et al 2016;Schaufler et al 2016). The non-photic serotonergic inputs in the SNC, for example, have activity influenced by nutrient intake, such a way, these inputs can stimulate the SCN at inappropriate times of the day due to poor eating habits, as overeating at night, which favors the development of the metabolic syndrome (Versteeg, Serlie, Kalsbeek, & Fleur, 2015). Nevertheless, the levels of 5-HT also exhibit circadian rhythmicity in several brain regions, including SCN, Pineal gland, raphe nuclei and corpus striatum (Barassin et al 2002;Versteeg, Serlie, Kalsbeek, & Fleur, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…The non-photic serotonergic inputs in the SNC, for example, have activity influenced by nutrient intake, such a way, these inputs can stimulate the SCN at inappropriate times of the day due to poor eating habits, as overeating at night, which favors the development of the metabolic syndrome (Versteeg, Serlie, Kalsbeek, & Fleur, 2015). Nevertheless, the levels of 5-HT also exhibit circadian rhythmicity in several brain regions, including SCN, Pineal gland, raphe nuclei and corpus striatum (Barassin et al 2002;Versteeg, Serlie, Kalsbeek, & Fleur, 2015). In experiments on mice, the disturbance of the circadian rhythm led to decrease in 5-HT expression in cell bodies (the dorsal and medial raphe nuclei) and projection areas (frontal cortex, caudate putamen, preoptic area and SCN), demonstrating a clear synergism between systems, which can contribute to the understanding of disorders (Matsumura et al 2015).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinical Advances of Recent Discoveries about the Interaction between Circadian and Serotoninergic Systems

Oliveira¹,

Marinho²,

Magalhaos³

2016

Int J Emerg Ment Health

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Early weaning modulates eating behavior and promotes hypofunction of the serotonergic (5HT) system in juvenile male rats

Tavares

Almeida

Souza

et al. 2020

Intl J of Devlp Neuroscience

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Early life stress (ELS) has been associated with developmental impairments. Early weaning (EW) is a postnatal stress model consisting of interruption of lactation and maternal care. The 5HT‐system has been associated with neurobehavioral modulations promoted by ELS. Thus, the present work aims to investigate the effects of early weaning on feeding behavior and serotonergic system of juvenile male rats. For this, rats were submitted to early (PND15) or natural (PND30) weaning and had the body weight, food intake in circadian phases, and food intake in response to fenfluramine assessed. mRNA expression of serotoninergic receptors (5HT1A and 5HT2C) and transporter (SERT) was assessed in the hypothalamus and brainstem, as well as NPY and POMC mRNA expression in hypothalamus. The results show that early weaning promoted changes in the percentage of weight gain during lactation period and increase in body weight at PND40. It was also observed that EW promoted increase and decrease in food intake in light and dark phase, respectively, and leads to a decreased action of fenfluramine on inhibition of food intake. In addition, early weaning promoted increased NPY and SERT mRNA expression in the hypothalamus and 5HT2C in the brainstem. Together, the data indicate that the stress caused by early weaning impairs the eating behavior of juvenile male rats through hypofunction of the 5HT‐system.

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Serotonin, a possible intermediate between disturbed circadian rhythms and metabolic disease

Cited by 45 publications

References 174 publications

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Clinical Advances of Recent Discoveries about the Interaction between Circadian and Serotoninergic Systems

Early weaning modulates eating behavior and promotes hypofunction of the serotonergic (5HT) system in juvenile male rats

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