Mitochondrial dynamics in the regulation of metabolism in the central nervous system. Several studies have dissected the role of mitochondrial dynamics in different brain areas and cell types regarding metabolic homeostasis. Within the ARC nucleus of the hypothalamus, alterations of mitochondrial dynamics caused by ablation of key proteins lead to altered glucose metabolism and energy balance or the opposite phenotype depending on the neuronal population studied. In the VMH nucleus, increases in the mitochondrial fission of neurons exert an improved glucose homeostasis. In hypothalamic microglia, decreased mitochondrial fission is associated with diet-induced obesity. In extra-hypothalamic areas, elevated mitochondrial fission in DVC neurons was discovered as a mechanism of diet-induced insulin resistance. In the present study from Patel et al., modulation of astrocytic mitochondrial dynamics, via activation or inactivation of Drp1, induces iNOS and ER stress in the DVC. As consequence, increased mitochondrial fission induces a defective anorectic insulin effect associated with body weight gain. ARC, arcuate nucleus of the hypothalamus; Drp1, dynamin-related protein 1; Drp1-S637A, constitutively active form of Drp1; Drp1-K38A, dominant negative form of Drp1; DVC, dorsal vagal complex; Hyp, hypothalamus; Mfn-1, mitofusin 1; Mfn-2, mitofusin 2; Opa1, mitochondrial dynamin-like GTPase 1; Ucp2, uncoupling protein 2; VMH, ventromedial nucleus of the hypothalamus. Information in this figure was obtained from: [[3], [4], [5], [6], [7], [8], [9],15]. ∗It has not been reported that OPA1 deletion in POMC neurons causes impaired glucose metabolism.
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