Caenorhabditis elegans as an emerging model for studying the basic biology of obesity

Abstract

The health problem of obesity and its related disorders highlights the need for understanding the components and pathways that regulate lipid metabolism. Because energy balance is maintained by a complex regulatory network, the use of a powerful genetic model like C. elegans can complement studies on mammalian physiology by offering new opportunities to identify genes and dissect complicated regulatory circuits. Many of the components that are central to governing human metabolism are conserved in the worm. Although the study of lipid metabolism in C. elegans is still relatively young, much progress has already been made in tracing out genetic pathways that regulate fat storage and in developing assays to explore different aspects of metabolic regulation and food sensation. This model system holds great promise for helping tease apart the complicated network of genes that maintain a proper energy balance.

Fig. 1.

Major fat-regulatory pathways are conserved between C. elegans and mammals. Many of the crucial regulators of lipid homeostasis in mammals serve similar functions in C. elegans. Regulators in the nervous system (blue) modulate fat metabolism, as well as feeding and food-related behaviors (they are able to regulate both aspects of fat balance by distinct mechanisms). Peripheral regulators of fat storage act directly in the tissues that contain the major fat depots for the organism (intestinal and hypodermal cells in C. elegans, shown in red). Some data suggest that fat regulators in the periphery can feed back and influence the nervous system, although the precise mechanism for this is currently unclear. Systems also exist to transport fats between cells and tissues (green). Prominent examples from each category are listed in the appropriate colors.

Fig. 2.

Methods to stain lipids in C. elegans. (A) Nile Red staining of a live animal. This composite image was made by overlaying fluorescence and DIC channels. Note that the animals shown in A–C are not matched for developmental stage or genotype; images are simply provided as examples for each staining methodology. (B) Sudan Black B staining of a fixed animal. (C) LipidTOX neutral lipid staining of a fixed animal. (D–E) Nile Red (D) and fatty acid-conjugated BODIPY staining (E) of a live animal. This higher magnification image, centered on the anterior intestinal cells, was taken with a spectral confocal microscope. The images in D and E were derived from spectral unmixing of the image in F to separate Nile Red from BODIPY fluorescence. Note that both intestinal and hypodermal lipids are visible in E. (F) Image of a live animal stained with both Nile Red and fatty acid-conjugated BODIPY, taken on a spectral confocal microscope. Note the extensive overlap of Nile Red-stained and fatty acid-conjugated BODIPY-stained lipid particles in the intestinal cells.