Differential Effects of Tissue-Specific Deletion of BOSS on Feeding Behaviors and Energy Metabolism

Abstract

Food intake and energy metabolism are tightly controlled to maintain stable energy homeostasis and healthy states. Thus, animals detect their stored energy levels, and based on this, they determine appropriate food intake and meal size. Drosophila melanogaster putative G protein-coupled receptor, Bride of sevenless (BOSS) is a highly evolutionarily conserved protein that responds to extracellular glucose levels in order to regulate energy homeostasis. To address how BOSS regulates energy homeostasis, we characterized a boss mutant by assessing its food intake and stored energy levels. Boss mutants exhibited increased food intake but decreased stored triacylglyceride levels. Using boss-GAL4 drivers, we found that boss is expressed in select tissues that are involved in nutrient sensing and food intake, in a subset of neurons in brain and chemosensory organs, in fat body, and in endocrine cells in gut (enteroendocrine cells). Flies with tissue-specific boss knockdowns in these tissues had abnormal stored energy levels and abnormal food intake. These results suggest that BOSS in either neurons or peripheral nutrient-sensing tissues affects energy homeostasis in ways that relate to the sensing of nutrients and regulation of food intake.

Loss of BOSS Causes Shortened Lifespan with Mitochondrial Dysfunction in Drosophila

“…We previously reported that energy state is reduced in boss mutant flies [11, 12]. Reducing cellular energy levels by starvation or exercise increases mitochondrial activity, and hence production of the energy source, ATP[9,38].…”

“…We previously reported that energy metabolism is disrupted in boss mutant flies, causing lean phenotype [11, 12]. The gut is one of the key tissues for aging regulation [17].…”

“…Moreover, the expression and activity of gastric lipases were decreased in boss mutant flies, producing a similar phenotype to that observed in aged control flies. Previously, we demonstrated that BOSS is expressed in enteroendocrine cells, and knockdown of boss in these cells lead to the lean phenotype [12]. Thus, it would be interesting to know whether BOSS expressed in enteroendocrine cells and/or in other tissues (such as neurons and the fat body) affect gut homeostasis.…”

“…We previously found that boss mutants are hyperphagic but paradoxically are lean, indicating that nutrient absorption might be disrupted [12]. If this were the case, more mitochondria would be required to generate more ATP.…”

“…BOSS was originally identified as a ligand of the receptor SEVENLESS and required for the development of the R7 photoreceptor neuron in the compound eye of Drosophila melanogaster [10]. Then we previously discovered that BOSS possesses a critical metabolic function: maintaining energy homeostasis [11, 12]. Insulin signaling is disrupted in boss mutant flies.…”