Study of Ets96B/ETV5 connects obesity and bipolar disorder at a molecular level

Williams MJ, Klockars A, Eriksson A, Voisin S, Dnyansagar R, Wiemerslage L, Kasagiannis A, Akram M, Kheder S, Ambrosi V, Hallqvist E, Fredriksson R, Schiöth HB. The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder. PLoS Genet. 2016 Jun 9;12(6):e1006104. PubMed PMID: 27280443; PubMed Central PMCID: PMC4900636.

From the abstract: "Several reports suggest obesity and bipolar disorder (BD) share some physiological and behavioural similarities. ... Here we demonstrate, using whole transcriptome analysis, that Drosophila Ets96B, homologue of obesity-linked gene ETV5, regulates cellular systems associated with obesity and BD. Consistent with a role in obesity and BD, loss of nervous system Ets96B during development increases triacylglyceride concentration, while inducing a heightened startle-response, as well as increasing hyperactivity and reducing sleep. Of notable interest, mouse Etv5 and Drosophila Ets96B are expressed in dopaminergic-rich regions, and loss of Ets96B specifically in dopaminergic neurons recapitulates the metabolic and behavioural phenotypes. Moreover, our data indicate Ets96B inhibits dopaminergic-specific neuroprotective systems. Additionally, we reveal that multiple SNPs in human ETV5 link to body mass index (BMI) and BD, providing further evidence for ETV5 as an important and novel molecular intermediate between obesity and BD. ... a connection between the obesity-linked gene ETV5 and bipolar disorder emphasizes a functional relationship between obesity and BD at the molecular level."

Fly cell and in vivo study of responses to lithium and valproate

Herteleer L, Zwarts L, Hens K, Forero D, Del-Favero J, Callaerts P. Mood stabilizing drugs regulate transcription of immune, neuronal and metabolic pathway genes in Drosophila. Psychopharmacology (Berl). 2016 May;233(9):1751-62. PMID: 26852229.

From the abstract: "Lithium and valproate (VPA) are drugs used in the management of bipolar disorder. ... We used Drosophila culture cells and adult flies to analyze the transcriptional effects of lithium and VPA and define mechanistic pathways. ... Transcriptional profiles were determined for Drosophila S2-cells and adult fly heads following lithium or VPA treatment. ... Lithium and VPA act on evolutionarily conserved pathways in Drosophila and mammalian models."