[HTML][HTML] Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity
Cell, 2013•cell.com
Mitochondria are key organelles in the maintenance of cellular energy metabolism and
integrity. Here, we show that mitochondria number decrease but their size increase in
orexigenic agouti-related protein (Agrp) neurons during the transition from fasted to fed to
overfed state. These fusion-like dynamic changes were cell-type specific, as they occurred in
the opposite direction in anorexigenic pro-opiomelanocortin (POMC) neurons. Interfering
with mitochondrial fusion mechanisms in Agrp neurons by cell-selectively knocking down …
integrity. Here, we show that mitochondria number decrease but their size increase in
orexigenic agouti-related protein (Agrp) neurons during the transition from fasted to fed to
overfed state. These fusion-like dynamic changes were cell-type specific, as they occurred in
the opposite direction in anorexigenic pro-opiomelanocortin (POMC) neurons. Interfering
with mitochondrial fusion mechanisms in Agrp neurons by cell-selectively knocking down …
Summary
Mitochondria are key organelles in the maintenance of cellular energy metabolism and integrity. Here, we show that mitochondria number decrease but their size increase in orexigenic agouti-related protein (Agrp) neurons during the transition from fasted to fed to overfed state. These fusion-like dynamic changes were cell-type specific, as they occurred in the opposite direction in anorexigenic pro-opiomelanocortin (POMC) neurons. Interfering with mitochondrial fusion mechanisms in Agrp neurons by cell-selectively knocking down mitofusin 1 (Mfn1) or mitofusin 2 (Mfn2) resulted in altered mitochondria size and density in these cells. Deficiency in mitofusins impaired the electric activity of Agrp neurons during high-fat diet (HFD), an event reversed by cell-selective administration of ATP. Agrp-specific Mfn1 or Mfn2 knockout mice gained less weight when fed a HFD due to decreased fat mass. Overall, our data unmask an important role for mitochondrial dynamics governed by Mfn1 and Mfn2 in Agrp neurons in central regulation of whole-body energy metabolism.
cell.com