Abstract
The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction. Here we show that SKN-1B acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-β), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins.
Highlights
It is necessary for animals to correctly sense and adapt to food
SKN-1B contributes to dietary restriction (DR) longevity, but is not necessarily essential
Neuronal SKN-1B controls satiety of skn-1b in the ASI neurons can mediate the extension in lifespan incurred by a food dilution DR protocol, suggesting that SKN-1B might be a general and essential mediator of DR (Bishop and Guarente, 2007)
Summary
Information on food cues is obtained via the sensory nervous system, integrated in the hypothalamus, and influences decisions about development, growth and behaviour [1,2] These signals dictate appropriate food intake and regulate metabolic homeostasis, but are not well understood. In the nematode worm C. elegans, chemosensory neurons detect nutritional status, and relay this information to other tissues via hormones [3] These hormones activate downstream intracellular mechanisms including the insulin/IGF-1-like signalling (IIS) and transforming growth factor-β (TGF-β) pathways which act to switch behaviour between roaming (looking for and consuming food), dwelling (consuming food) and quiescence (a sleep-like state linked to satiety) depending on nutritional availability [4,5,6,7]. Adaptation to food cues requires physiological changes, and mitochondrial networks are modulated to maximise energy output [8] Combined, these appropriate behavioural and physiological changes mean that food levels are correctly perceived, nutrient intake is regulated, and metabolic balance is maintained
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call