AUTHOR=Liao Sifang , Post Stephanie , Lehmann Philipp , Veenstra Jan A. , Tatar Marc , Nässel Dick R. 

TITLE=Regulatory Roles of Drosophila Insulin-Like Peptide 1 (DILP1) in Metabolism Differ in Pupal and Adult Stages

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00180

DOI=10.3389/fendo.2020.00180

ISSN=1664-2392

ABSTRACT=<p>The insulin/IGF-signaling pathway is central in control of nutrient-dependent growth during development, and in adult physiology and longevity. Eight insulin-like peptides (DILP1–8) have been identified in <italic>Drosophila</italic>, and several of these are known to regulate growth, metabolism, reproduction, stress responses, and lifespan. However, the functional role of DILP1 is far from understood. Previous work has shown that <italic>dilp1</italic>/DILP1 is transiently expressed mainly during the pupal stage and the first days of adult life. Here, we study the role of <italic>dilp1</italic> in the pupa, as well as in the first week of adult life, and make some comparisons to <italic>dilp6</italic> that displays a similar pupal expression profile, but is expressed in fat body rather than brain neurosecretory cells. We show that mutation of <italic>dilp1</italic> diminishes organismal weight during pupal development, whereas overexpression increases it, similar to <italic>dilp6</italic> manipulations. No growth effects of <italic>dilp1</italic> or <italic>dilp6</italic> manipulations were detected during larval development. We next show that <italic>dilp1</italic> and <italic>dilp6</italic> increase metabolic rate in the late pupa and promote lipids as the primary source of catabolic energy. Effects of <italic>dilp1</italic> manipulations can also be seen in the adult fly. In newly eclosed female flies, survival during starvation is strongly diminished in <italic>dilp1</italic> mutants, but not in <italic>dilp2</italic> and <italic>dilp1</italic>/<italic>dilp2</italic> mutants, whereas in older flies, only the double mutants display reduced starvation resistance. Starvation resistance is not affected in male <italic>dilp1</italic> mutant flies, suggesting a sex dimorphism in <italic>dilp1</italic> function. Overexpression of <italic>dilp1</italic> also decreases survival during starvation in female flies and increases egg laying and decreases egg to pupal viability. In conclusion, <italic>dilp1</italic> and <italic>dilp6</italic> overexpression promotes metabolism and growth of adult tissues during the pupal stage, likely by utilization of stored lipids. Some of the effects of the <italic>dilp1</italic> manipulations may carry over from the pupa to affect physiology in young adults, but our data also suggest that <italic>dilp1</italic> signaling is important in metabolism and stress resistance in the adult stage.</p>