Insulin, cGMP, and TGF-β Signals Regulate Food Intake and Quiescence in C. elegans: A Model for Satiety

You, Young-Jai; Kim, Jeongho; Raizen, David M.; Avery, Leon

doi:10.1016/j.cmet.2008.01.005

Cited by 261 publications

(378 citation statements)

References 44 publications

Supporting

Mentioning

366

Contrasting

Order By: Relevance

“…Two C. elegans TGF-β ligands have been well characterized: DAF-7 and DBL-1. Whereas DAF-7 regulates multiple physiological traits, including diapause stage (dauer) entry, metabolism (8)(9)(10)(11), DBL-1 controls body morphology, innate immunity, and reproductive aging (9,12,13). Here we report that the activity of DBL-1 is critical for adult animals to learn to avoid the smell of pathogenic bacteria.…”

mentioning

confidence: 87%

DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning

Zhang¹,

Zhang

2012

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

View full text Add to dashboard Cite

The TGF-β superfamily is conserved throughout metazoan, and its members play essential roles in development and disease. TGF-β has also been implicated in adult neural plasticity. However, the underlying mechanisms are not well understood. Here we report that DBL-1, a Caenorhabditis elegans TGF-β homolog known to control body morphology and immunity, is essential for aversive olfactory learning of potentially harmful bacteria food. We show that DBL-1 generated by the AVA command interneurons, which are critical for sensorimotor responses, regulates aversive olfactory learning, and that the activity of the type I TGF-β receptor SMA-6 in the hypodermis is needed during adulthood to generate olfactory plasticity. These spatial and temporal mechanisms are critical for the DBL-1 signaling to achieve its diverse functions in development and adult neural plasticity. Interestingly, aversive training decreases AVA calcium response, leading to an increase in the DBL-1 signal secreted from AVA, revealing an experience-dependent change that can underlie the role of TGF-β signaling in mediating plasticity.experience-dependent secretion | molecular and cellular mechanisms for TGF-beta pathway in learning

show abstract

mentioning

confidence: 87%

DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning

Zhang¹,

Zhang

2012

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

View full text Add to dashboard Cite

show abstract

“…This quiescence is missing in daf-7 mutants, showing that the homolog of the human TGF-b pathway is involved. 19 Expression of the wild-type daf-7 gene in the pair of amphid sensilla chemosensory neurons (ASI) of daf-7-mutant C. elegans, however, completely rescues the quiescence defect. Thus, the quiescence after fasting and re-feeding appears to be mediated by daf-7.…”

Section: Introductionmentioning

confidence: 99%

“…The act-5 gene encodes a microvillus-specific actin required for absorbing nutrients from the intestine, and an act-5 mutation decreases quiescence. 19 The elg-3 or elg-21 gene codes for proprotein convertase (PC1/3) or carboxypeptidase (CPA), respectively. Mutations of egl-3 and elg-21 eliminate most peptide signals and abolish the quiescence, suggesting a dependence of quiescence on the signaling of the PC1/3 and/or CPA protein(s).…”

Section: Introductionmentioning

confidence: 99%

Caenorhabditis elegans as a model for obesity research

Zheng

Greenway

2011

Int J Obes

View full text Add to dashboard Cite

Caenorhabditis elegans (C. elegans) is a small nematode that conserves 65% of the genes associated with human disease, has a 21-day lifespan, reproductive cycles of 3 days, large brood sizes, lives in an agar dish and does not require committee approvals for experimentation. Research using C. elegans is encouraged and a Caenorhabditis Genetics Center (CGC, Minnesota) is funded by the National Institutes of Health-National Center for Research Resources. Many genetically manipulated strains of C. elegans are available at nominal cost from the CGC. Studies using the C. elegans model have explored insulin signaling, response to dietary glucose, the influence of serotonin on obesity, satiety, feeding and hypoxia-associated illnesses. C. elegans has also been used as a model to evaluate potential obesity therapeutics, explore the mechanisms behind single gene mutations related to obesity and to define the mechanistic details of fat metabolism. Obesity now affects a third of the US population and is becoming a progressively more expensive public health problem. Faster and less expensive methods to reach more effective treatments are clearly needed. We present this review hoping to stimulate interest in using the C. elegans model as a vehicle to advance the understanding and future treatment of obesity.

show abstract

“…In invertebrates and vertebrates, appetite, locomotor activity, and sleep rhythms are all driven by nutritional state (1)(2)(3)(4)(5)(6)(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).…”

mentioning

confidence: 99%

“…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 food, with high-quality food defined as a superior supporter of worm growth (1,4).…”

mentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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...

show abstract

Insulin, cGMP, and TGF-β Signals Regulate Food Intake and Quiescence in C. elegans: A Model for Satiety

Cited by 261 publications

References 44 publications

DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning

DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning

Caenorhabditis elegans as a model for obesity research

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

Contact Info

Product

Resources

About