Acer, a homologue of the human angiotensin-1 converting enzyme, modulates
      the response of sleep, glycogen storage, lifespan, fecundity and stress
      resistance to diet in Drosophila melanogaster
Creators: name: Glover, Zoe
Publisher: name: Lancaster University
Year: 2017
Subjects: Drosophila
Acer

description: Human angiotensin-1–converting-enzyme (ACE) plays a primary role in the
      regulation of blood pressure and electrolytes as part of the
      Renin-Angiotensin System (RAS) in humans. Renin cleaves angiotensinogen to
      angiotensin I and ACE regulates the vasoconstriction of blood vessels by
      converting angiotensin-1 to angiotensin-2 (a potent vasoconstrictor) and
      also by breaking down bradykinin (a potent vasodilator). Renin is
      regulated by a feedback loop mechanism and is inhibited by higher
      concentrations of angiotensin-2. A lack of or inhibition of ACE can lead
      to a reduction in blood pressure (BP) and may reduce the risk of diabetic
      nephropathy as high BP and high fluid retention can cause swelling in the
      kidneys. ACE inhibitors are used as treatments for these conditions as
      well as treating congestive heart failure (Stanley &amp; Samson,
      2002). ACE expression has been found in human adipose cells (Jonsson, et
      al., 1994) and ACE expression in this tissue was reduced when rats were
      treated with the ACE inhibitor Enalapril (Santos, et al., 2009). Currently
      ACE’s role in this tissue is unknown and therefore the study of the
      Drosophila homolog ACER, which is expressed within the fly fat body which
      is similar in structure to human adipose cells, may highlight a role for
      ACE in adipose tissue. To investigate the role of ACE-like enzymes in
      dietary effects on ageing-related and circadian health, function and
      metabolism we are studying ACER, a homologue of human ACE, in the fruit
      fly Drosophila melanogaster. Previous studies (Taylor, et al., 1996;
      Carhan, et al., 2010) have shown that Acer is expressed in the embryonic
      heart, adult head and adult fat body of the fly. The expression in the fat
      body is particularly interesting as the fly fat body acts like the human
      liver and adipose cells where ACE in humans is expressed. Acer’s
      expression in the head shows a circadian cycle and appears to be regulated
      by the circadian gene Clock. AcerΔ mutant flies exhibit normal circadian
      locomotor rhythms but show defects in the regulation of sleep, and the ACE
      inhibitor, Fosinopril, fed to flies disrupts night time sleep in the same
      way. This suggests a role for ACER in a circadian phenotypes in Drosophila
      and therefore a potential circadian role for ACE in humans (Carhan, et
      al., 2010). The present study has found the effect of the loss of Acer
      expression in the Acer deletion mutant (AcerΔ) was complex and was often
      dependent on genetic background and sex. AcerΔ mutants responded normally
      to dietary restriction (DR) for both sex and background therefore, Acer
      was not required for the DR response to lifespan. Lipid storage in the
      AcerΔ mutants was unaffected by the loss of Acer expression but glycogen
      storage was reduced on high food levels and did not show the normal
      increase in storage with increasing food compared to controls. Thus,
      indicating a role for Acer in the modulation of glycogen storage. The
      genetic backgrounds analysed in this study were the outbred whiteDahomey
      (wDah) and inbred white1118 (w1118) backgrounds which did show a
      difference in the effect of the loss of Acer for certain phenotypes.
      Fecundity in AcerΔ females was lower than in controls in the more fecund
      wDah background but not in the less fecund w1118 background. Sleep also
      showed an altered response between the backgrounds and sexes to changing
      diet in AcerΔ mutants. AcerΔ mutants were starvation and oxidative stress
      resistant but only in the wDah background and showed sensitivity when
      compared to controls in the w1118 background. To investigate Acer’s role
      in the response to nutrition the effect of the loss of Acer on
      drosophila-insulin-like peptides (dilps) was investigated. Altered
      transcript levels of dilps in the head and body of the fly in AcerΔ
      mutants indicated a possible link between Acer and the IIS
      (insulin/IGF-like signalling) nutrient-sensing pathway. In this study a
      role for Acer in the modulation of nutrient responsive phenotypes was
      established.