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キーワード:
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要旨:
To unravel the evolutionarily conserved genetic
network underlying energy homeostasis, we performed
a systematic in vivo gene knockdown screen
in Drosophila. We used a transgenic RNAi library
enriched for fly orthologs of human genes to functionally
impair about half of all Drosophila genes specifically
in adult fat storage tissue. This approach
identified 77 genes, which affect the body fat
content of the fly, including 58 previously unknown
obesity-associated genes. These genes function in
diverse biological processes such as lipid metabolism,
vesicle-mediated trafficking, and the universal
store-operated calciumentry (SOCE). Impairment
of the SOCE core component Stromal interaction
molecule (Stim), as well as other components of the
pathway, causes adiposity in flies. Acute Stim
dysfunction in the fat storage tissue triggers hyperphagia
via remote control of the orexigenic short
neuropeptide F in the brain, which in turn affects
the coordinated lipogenic and lipolytic gene regulation,
resulting in adipose tissue hypertrophy.
