Manipulating mitochondrial dynamics in the NTS prevents diet-induced deficits in brown fat morphology and glucose uptake

Hindbrain REV-ERB nuclear receptors regulate sensitivity to diet-induced obesity and brown adipose tissue pathophysiology

“…Specifically, the NTS of the DVC projects to thalamic regions that regulate activity in the pre-sympathetic dorsal raphe nuclei (DRN) [ 35 ]. Through these neural networks, the DVC can modulate BAT activity in response to the humoral and neural feeding signals it receives from the periphery [ [36] , [37] , [38] ]. Of the several factors and receptors that mediate DVC control of energy balance, we measured gene expression for Gcg (glucagon-like peptide), Insr (insulin receptor) , Lepr (leptin receptor), and Calcr (calcitonin receptor) from microdissected DVCs in control and DVC RDKO animals fed HFD.…”

“…The decrease in Calcr (CTR) gene expression was intriguing because CTRs are G-protein coupled receptors that are often found in complex with a receptor activating modifying protein (RAMP) to form the heterodimerized amylin receptor [ 41 ]. Activation of CTRs in the DVC has been found to regulate not only food intake, but energy expenditure through indirect NTS projections to the DRN that modulate SNS-stimulated BAT activity [ [36] , [37] , [38] , 42 , 43 ]. Therefore, we measured BAT expression of tyrosine hydroxylase ( Th ) to determine disruptions in general SNS outflow and found that Th RNA and TH protein expression were decreased in the DVC RDKO animals ( Figure 5 B–D).…”

Whole blood mitochondrial copy number in clinical populations with mood disorders: a meta-analysis

“…In the context of depressive disorders, both MDD and BD have been linked to mitochondrial disfunction in the brain and in the periphery (1,2,4,9–14). In MDD patients depressive episodes are linked to higher levels of oxidative damage markers and lower levels of antioxidant compounds in serum or red blood cell samples (15). Altered mitochondrial gene expression has been observed in postmortem dorsolateral prefrontal cortex (16), and increased reactive oxygen species, reduced antioxidant levels and inflammatory markers have been found across tissue types (4,17,18).…”

“…Generally, a higher relative copy number is taken to indicate more mitochondria. mtDNAcn disruption has been demonstrated in diseases as disparate as various cancers (15), neurodegenerative disorders (24,28,29), psychosis (19,30), and substance use disorders (31–33). Blood is readily accessible in human populations, and amenable to resampling after disease progression or treatment, making blood mtDNAcn specifically a robust candidate for a mood disorder biomarker.…”