SIK-mediated regulation of feeding behavior and fat metabolism in Caenorhabditis elegans
The relationship between fat accumulation and metabolic disorders, such as obesity, is well documented. However, the precise control that the nervous system retains on fat regulation in peripheral tissues is undefined. Oil Red-O, a lipophilic dye used to quantify fat stores, has shown that mutation of the sole Salt-Inducible Kinase (SIK) ortholog (kin-29) in Caenorhabditis elegans produces an increase in fat stores. Rescuing expression of kin-29 in a subset of sensory neurons results in an abatement of peripheral fat stores, suggesting kin-29 may act in the sensory neurons of C. elegans. In addition, kin-29 has been shown to regulate feeding behavior, with kin-29 mutants exhibiting hyperforaging in the presence of food. To investigate how KIN-29 couples the perception of nutrient availability to the regulation of peripheral fat stores; kin-29 mutant animals were fed high, medium, and poor quality food and their peripheral fat levels analyzed. kin-29 mutant animals displayed high body fat regardless of the food source. However, high quality food did reduce kin-29 mutants hyperforaging suggesting that fat composition is critical to feeding behavior. To further understand the neural regulation of fat stores the Ca2+-dependent activator protein for secretion (CAPS) ortholog (unc-31) was mutated, shutting down neuropeptide secretion. On medium and high quality foods kin-29's fat stores were partially rescued displaying that neuronal exocytosis may be involved in kin-29's mutant's fat storage.
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