Appetite regulation is controlled in part by neurons in the lateral hypothalamus, which secrete neuropeptides in response to signals from the body about its energy reserves. In particular, a pair of neuron populations called AGRP (agouti-gene related protein) and POMC (pro-opiomelanocortin) appear to have an opposing effect, with AGRP stimulating feeding and POMC inhibiting it. In this month's issue of Cell, the effect of mitochondrial dynamics on both neuronal populations has been investigated by Dietrich et al and Schneeberger et al. In AGRP neurons, food deprivation leads to a breakup of the mitochondrial network established in the normal-chow diet, whereas feeding of a high fat diet leads to greater aggregation of the mitochondrial network. This effect appears to be population-specific, and has the effect of causing weight gain by increased fat mass.
Knockout of mfn1 does not lead to phenotypic variation on standard chow diet, but leads to fat mass gain in female mice on a high fat diet. No effect is observed in males. Mfn2 knockout leads to decreased weight gain in female mice fed ad libitum on normal chow, with the only observed compensating factor being an increase in respiratory exchange ratio (a measurement of the use of glucose instead of fat in metabolism, which AGRP neurons are believed to play a role in regulating). Both genders gained less weight on a high fat diet if mfn2 was knocked out.
Knockout of mfn1 does not lead to phenotypic variation on standard chow diet, but leads to fat mass gain in female mice on a high fat diet. No effect is observed in males. Mfn2 knockout leads to decreased weight gain in female mice fed ad libitum on normal chow, with the only observed compensating factor being an increase in respiratory exchange ratio (a measurement of the use of glucose instead of fat in metabolism, which AGRP neurons are believed to play a role in regulating). Both genders gained less weight on a high fat diet if mfn2 was knocked out.
