Editors' ChoiceMetabolism

BMPing Up Metabolism

Science Signaling  12 Jan 2010:
Vol. 3, Issue 104, pp. ec7
DOI: 10.1126/scisignal.3104ec7

It has long been appreciated that bone morphogenetic proteins (BMPs) regulate patterning and morphological processes in animals as diverse as hydra and human and do so in many different tissues at different developmental stages. BMPs play a role in specifying adipose cell fate in mammals, and Ballard et al. report that one of these cytokines, Gbb (glass bottom boat, the ortholog of mammalian BMP5,6,7,8) regulates lipid metabolism in the fruit fly Drosphila melanogaster. Gbb was so named because gbb loss-of-function mutant larvae are nearly transparent due to decreased opacity of the fat body, an organ that stores fats and sugars. Ballard and colleagues noted that these mutants also showed delayed progression through developmental stages, smaller overall body size, and abnormal lipid accumulation in the fat body, phenotypes that are similar to nutrient-deprived wild-type (WT) larvae and to target of rapamycin (TOR) signaling mutants. Like Tor mutants, gbb larvae contained substantially less lipids and sugars relative to body weight than did WT larvae and showed enhanced uptake of a fluorescently labeled fatty acid (C12) by the gut epithelium, suggesting that the starvation response was activated. Both gbb mRNA and phosphorylated Mad (pMad) were detected in fat body cells in WT but not in gbb mutant larvae. Knocking down gbb in the fat body of WT larvae by tissue-specific RNA interference phenocopied the larval transparency and increased C12 uptake gbb phenotypes, and expression of a transgenically encoded constitutively active version of the Gbb receptor Sax in the fat body of gbb mutants rescued these phenotypes. The amount of nuclear pMad was reduced in nutrient-deprived WT larvae as compared with fed controls, which implies that Gbb signaling responds to metabolic status in addition to regulating it. Although many phenotypes were shared between starved WT larvae and fed gbb mutants, these phenotypes depended on molecularly distinct processes, as illustrated by the observation that different, although partially overlapping, sets of genes were transcriptionally regulated in the two types of larvae. Given that many molecular regulators of nutrient storage and mobilization are conserved between flies and humans, it is thus possible that, in addition to playing a role in patterning adipose tissue, BMPs may also regulate energy homeostasis.

S. L. Ballard, J. Jarolimova, K. A. Wharton, Gbb/BMP signaling is required to maintain energy homeostasis in Drosophila. Dev. Biol. 337, 375–385 (2010). [PubMed]