Loss of angiotensin-converting enzyme-related (ACER) peptidase disrupts behavioural and metabolic responses to diet in Drosophila melanogaster

Abstract

Drosophila Acer (Angiotensin-converting enzyme-related) encodes a member of the angiotensin-converting enzyme (ACE) family of metallopeptidases that in mammals play roles in the endocrine regulation of blood homeostasis. ACE is also expressed in adipose tissue, where it is thought to play a role in metabolic regulation. Drosophila ACER is expressed in the adult fat body of the head and abdomen and is secreted into the haemolymph. Acer null mutants have previously been found to have reduced night-time sleep and greater sleep fragmentation. ACER may thus be part of a signalling system linking metabolism with sleep. To further understand the role of ACER in response to diet, we measured sleep and other nutrientresponsive phenotypes in Acer null flies under different dietary conditions. We show that loss of Acer disrupts the normal response of sleep to changes in nutrition. Other nutrient-sensitive phenotypes, including survival and glycogen storage, were also altered in the Acer mutant but lipid storage was not. Although the physiological substrate of the ACER peptidase has not been identified, an alteration of the normal nutrient-dependent control of Drosophila insulin-like peptide 5 protein in the Acer mutant suggests insulin/IGF-like signalling as a candidate pathway modulated by ACER in the nutrient-dependent control of sleep, survival and metabolism.

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Rescue Memory Defects inDrosophila-Expressing Alzheimer’s Disease-Related Transgenes Independently of the Canonical Renin Angiotensin System

“…Some ACE-like factors have been shown to be affected by ACE-Is including Acer and Ance (Williams et al, 1996;Houard et al, 1998) however, the targets of either protein have yet to be identified. Acer null mutants have also been shown to exhibit disruptions in night-time sleep and sleep fragmentation (Carhan et al, 2011) as well as altered behavioural and metabolic responses to diet (Glover et al, 2019). However, these flies develop normally to adulthood, suggesting that major developmental or signaling pathways have not been affected.…”

Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila

“…This raises the possibility that Gbs-76A contributes to the regulation of Lipin phosphorylation. Female Lipin DNLS flies less efficiently down-regulate Acer, a gene that is involved in glycogen metabolism as well (49) and they less efficiently up-regulate glycolytic enzymes. This suggests that, similar to the males, females cannot make efficient use of energy reserves, although lipolytic enzymes are not as much affected in females as they are in males.…”

“…Acer mutants of Drosophila have reduced glycogen stores. It is, therefore, somewhat surprising that these mutants exhibit slightly increased starvation resistance (49). Thus, reduced down-regulation of Acer in the Lipin DNLS mutant may contribute to the starvation sensitivity of the mutant.…”

Identification and Integrated Analysis of MicroRNA and mRNA Expression Profiles During Agonistic Behavior in Chinese Mitten Crab (Eriocheir sinensis) Using a Deep Sequencing Approach

“…Based on the above studies, ACE, which was significantly upregulated in our results, plays a key role in the RAS pathway. A series of studies show that ACE is related to glucose and lipid metabolism (Vaughan et al, 2016;Glover et al, 2019). In addition, ACE modulates behavioral and metabolic responses to diet in Drosophila melanogaster (Glover et al, 2019).…”

“…A series of studies show that ACE is related to glucose and lipid metabolism (Vaughan et al, 2016;Glover et al, 2019). In addition, ACE modulates behavioral and metabolic responses to diet in Drosophila melanogaster (Glover et al, 2019). Moreover, ACE may alter anxiety-like behavior (Wang L.A. et al, 2018) and cognitive ability (Gamba et al, 2019) by mediating the RAS.…”