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Mitochondrial dynamics refers to the constant remodelling of mitochondrial populations by multiple cellular pathways which help maintain mitochondrial health and function. Disruptions to mitochondrial dynamics often leads to mitochondrial dysfunction, which is frequently associated with disease in rodents and humans. Consistent with this, obesity is associated with reduced mitochondrial function in white adipose tissue, partly via alterations in mitochondrial dynamics. Several proteins are known to regulate mitochondrial dynamics including the E3 ubiquitin ligase MARCH5; however, the role of these proteins in adipocytes has been poorly studied. Here, we show that MARCH5 is regulated by PPARγ during adipogenesis and is correlated with fat mass across a panel of genetically diverse mouse strains, in ob/ob mice, and in humans. Furthermore, manipulation of MARCH5 expression both in vitro and in vivo alters mitochondrial function, affects cellular metabolism and leads to differential regulation of several metabolic genes. Thus, our data demonstrate a link between mitochondrial dynamics and metabolism which defines MARCH5 as a critical link between these interconnected pathways.
This article was published in the following journal.
Name: American journal of physiology. Endocrinology and metabolism
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To test the hypothesis that stimulation of PPAR-γ receptors has a therapeutic role in the treatment of asthma.
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A DNA amplification technique based upon the ligation of OLIGONUCLEOTIDE PROBES. The probes are designed to exactly match two adjacent sequences of a specific target DNA. The chain reaction is repeated in three steps in the presence of excess probe: (1) heat denaturation of double-stranded DNA, (2) annealing of probes to target DNA, and (3) joining of the probes by thermostable DNA ligase. After the reaction is repeated for 20-30 cycles the production of ligated probe is measured.
A forkhead box transcription factor that is a major target of INSULIN signaling and regulator of metabolic homeostasis in response to OXIDATIVE STRESS. It binds to the insulin RESPONSE ELEMENT (IRE) and the related Daf-16 family binding element (DBE). Its activity is suppressed by insulin and it also regulates OSTEOBLAST proliferation, controls bone mass, and skeletal regulation of GLUCOSE metabolism. It promotes GLUCONEOGENESIS in HEPATOCYTES and regulates gene expression in ADIPOSE TISSUE. It is also an important CELL DEATH regulator. Chromosomal aberrations involving the FOXO1 gene occur in RHABDOMYOSARCOMA.
One of the PPAR nuclear transcription factors.
A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.
A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
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