Drosophila FIT is a protein-specific satiety hormone essential for feeding control

Abstract

Protein homeostasis is critical for health and lifespan of animals. However, the mechanisms for controlling protein feeding remain poorly understood. Here we report that in Drosophila, protein intake-induced feeding inhibition (PIFI) is specific to protein-containing food, and this effect is mediated by a fat body (FB) peptide named female-specific independent of transformer (FIT). Upon consumption of protein food, FIT expression is greatly elevated. Secreted FIT peptide in the fly haemolymph conveys this metabolic message to the brain, thereby promoting the release of Drosophila insulin-like peptide 2 (DILP2) and suppressing further protein intake. Interestingly, Fit is a sexually dimorphic gene, and consequently protein consumption-induced insulin release, as well as protein feeding behaviour, are also dimorphic between sexes. Thus, our findings reveal a protein-specific satiety hormone, providing important insights into the complex regulation of feeding decision, as well as the sexual dimorphism in feeding behaviour.

Sex-specific transcriptomic responses to changes in the nutritional environment

“…Interestingly, fit has also been implicated in protein satiety in a sex-specific manner [65]. Following the ingestion of protein-rich food, fit expression increases in both sexes (although more so in females than males), but only supresses protein appetite in females [65]. Both fit and Obp99B were found to be significantly altered in a sexspecific way when flies were starved, further cementing their role in nutrient response [66].…”

“…Known to be sexually dimorphic in expression, fit has been found to be rapidly upregulated in male heads during the process of male courtship and mating, along with another antagonistic candidate Odorant binding protein 99b, Obp99B [63,64]. Interestingly, fit has also been implicated in protein satiety in a sex-specific manner [65]. Following the ingestion of protein-rich food, fit expression increases in both sexes (although more so in females than males), but only supresses protein appetite in females [65].…”

Dietary Amino Acids Impact LRRK2-induced Neurodegeneration in Parkinson’s Disease Models

“…Food intake, measured by ingestion of blue dye-labeled food, is inversely proportional to dietary amino acid concentration in 6-week-old flies (Fig. S1b), likely due to the rapid satiating effects of high amino acid diets, as has been reported for high protein diets in Drosophila (Sun et al 2017), rodents (Solon-Biet et al 2014) and humans (Westerterp-Plantenga et al 2009). LRRK2 toxicity is kinase-dependent (Greggio et al 2006) and to probe whether dietary amino acid concentration affects LRRK2 expression or activity in a manner that might modulate PD-related phenotypes, we assessed LRRK2 expression and LRRK2 G2019S auto-phosphorylation at Ser1292 as a readout of its kinase activity (Sheng et al 2012).…”

A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion

“…The fat body is reported to secrete factors into the hemolymph that modulate insulin expression and release from the IPCs [11][12][13]15,16,57 . To investigate whether this tissue also is involved in the insulinostatic hypoxia-adaptation response, we measured fat-body expression of bnl to determine whether this tissue experiences hypoxia under btl knockdown in the tracheae.…”