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Home > Departments > Cell Biology > Jacques MONTAGNE : Growth and Metabolism

Jacques MONTAGNE : Group Presentation

In our team, we are focusing on lipid metabolism at the integrative level of an entire organism, using the fruitfly model Drosophila melanogaster. To address these issues, we are combining molecular genetic, imaging and biochemical approaches.

Lipid metabolism plays a central role in several human pathologies, including metabolic syndrome, obesity, diabetes, cancers and neurological disorders. Our main research axis is centered on a systematic analysis of genes encoding fatty acid metabolic effectors (enzymes, receptors, carriers…). We are using the power of Drosophila genetics to evaluate the importance of the various metabolic branches in each organ and their input on body homeostasis. We also aim to characterize the functional links that coordinate growth regulation with metabolism both at the cellular and organismal levels.

Steroid hormones regulate metabolism and development. In Drosophila, the steroid hormone 20-hydroxy-ecdysone (20E), synthesized before each molt, regulates developmental transitions. We have shown that 20E regulates its biogenesis through a step-forward process (Figure 1). We are currently investing how lipid metabolism within the fat body —an insect organ with hepatic and adipose functions— regulates the biogenesis of 20E.

Figure 1: Model for steroidogenesis auto-regulation.
Peaks of ecdysone are required to trigger molting transitions. Ecdysone is produced within the prothoracic gland and then converted to the active 20-hydroxy-ecdysone (20E). In target tissues, 20E induces the expression of a cascade of nuclear receptors. We have shown that this cascade acts through a non-conventional hierarchy within the prothoracic gland. In this tissue, DHR3 acts as a repressor of steroidogenesis. The other nuclear receptors (EcR, E75, βFtz-f1) act to modulate the kinetics of DHR3 activity, thereby narrowing ecdysone production.

In insects, the oenocytes —cells localized underneath the abdominal epidermis— are tightly associated with lipid metabolism. We have shown that a very long chain fatty acid (VLCFA) produced within the larval oenocytes is absolutely required for the watertightness of the respiratory system (Figure 2). We are now working on the metabolic pathway that sustains the biogenesis of the fatty acid precursors of the cuticular hydrocarbons in adult flies.

Figure 2: Larval oenocytes are absolutely required for the watertightness of the respiratory system.
A VLCFA produced within the oenocytes is necessary for the transfer of lipids from the spiracular gland to the air openings of the tracheal system, which brings oxygen to the demanding organs.

Nutrition is central for body homeostasis. We have shown that Drosophila deficient for fatty acid synthesis are extremely sensitive to dietary sugar. We are now working to decipher the molecular bridge that link together fatty acid metabolism with insulin and nutrient response.

Keywords:

Metabolism, Homeostasis, Physiology, Cell growth, Fatty acid, Nutrients, Insulin, Drosophila.

Contact :


MONTAGNE Jacques [Senior Researcher - CNRS]
Growth& Metabolism in Drosophila [Leader]
01 69 82 46 07 (bureau) Gif - Bât 21

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