Neural and endocrine regulation of nutrient and energy homeostasis

Living organisms need energy for  functions like  growth, locomotion,
defense  and reproduction.  In multi-cellular animals built-in
homeostatic mechanisms control nutrient intake according to energy
needs and regulate energy requiring processes according to nutrient
availability.  Break down of energy and nutrient balance is
responsible for metabolic disorders like diabetes and obesity which
affects ~0.5 billion people globally according to current estimates.
However, exact reasons of why the homeostatic mechanisms fail leading
to these diseases are still not clear. Past few decades of research
show that neural and endocrine centers play a key role in maintaining
nutrient and energy homeostasis.  But intricate nature and complex
distribution of these regulatory centers has precluded a complete
understanding of the mechanisms involved.
        To investigate the regulatory mechanisms of energy homeostasis I use
genetic model organism Drosophila with less complex neural and
endocrine systems. The conserved insulin-signaling pathway maintains
nutrient homeostasis by sensing and regulating nutrient levels
available for energy production.  Over the past few years evidence has
begun to accumulate that insulin production and secretion as well as
cellular responsiveness to insulin are subject to regulation by
microRNAs. I will present evidence from my recent paper that
Drosophila microRNA miR-14 acts in the insulin producing
neurosecretory cells in the adult brain to control fat metabolism.
miR-14 allows the fly to manage resource mobilization in a
nutritionally variable environment by regulating insulin gene
expression. I will also present on going work on a novel mechanism of
nutrient sensing and homeostatic maintenance that involves the highly
conserved hypoxia-signaling pathway. I will show evidence that
metabolic intermediates play a direct role in this process.
        Further, I will discuss my future plans to investigate mechanisms of
nutrient sensing and maintenance of energy homeostasis by the neural
and endocrine centers using Drosophila and mammalian model systems.