Epidermal tyrosine catabolism is crucial for metabolic homeostasis and survival against high-protein diets in Drosophila

Author:

Kosakamoto Hina1ORCID,Miura Masayuki2ORCID,Obata Fumiaki13ORCID

Affiliation:

1. Laboratory for Nutritional Biology, RIKEN Center for Biosystems Dynamics Research 1 , Kobe, Hyogo 650-0047 , Japan

2. Graduate School of Pharmaceutical Sciences, The University of Tokyo 2 Department of Genetics , , Bunkyo-ku, Tokyo 113-0033 , Japan

3. Graduate School of Biostudies, Kyoto University 3 Laboratory of Molecular Cell Biology and Development , , Kyoto 606-8501 , Japan

Abstract

ABSTRACT The insect epidermis forms the exoskeleton and determines the body size of an organism. How the epidermis acts as a metabolic regulator to adapt to changes in dietary protein availability remains elusive. Here, we show that the Drosophila epidermis regulates tyrosine (Tyr) catabolism in response to dietary protein levels, thereby promoting metabolic homeostasis. The gene expression profile of the Drosophila larval body wall reveals that enzymes involved in the Tyr degradation pathway, including 4-hydroxyphenylpyruvate dioxygenase (Hpd), are upregulated by increased protein intake. Hpd is specifically expressed in the epidermis and is dynamically regulated by the internal Tyr levels. Whereas basal Hpd expression is maintained by insulin/IGF-1 signalling, Hpd induction on high-protein diet requires activation of the AMP-activated protein kinase (AMPK)–forkhead box O subfamily (FoxO) axis. Impairment of the FoxO-mediated Hpd induction in the epidermis leads to aberrant increases in internal Tyr and its metabolites, disrupting larval development on high-protein diets. Taken together, our findings uncover a crucial role of the epidermis as a metabolic regulator in coping with an unfavourable dietary environment.

Funder

Japan Agency for Medical Research and Development

Japan Society for the Promotion of Science

Uehara Memorial Foundation

Japan Science and Technology Agency

Publisher

The Company of Biologists

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