Sensitive and early detection of mitochondrial dysfunction in the liver of NASH model mice by PET imaging with 18F-BCPP-BF

Toshihiro, Sakai; Ohba, Hideki; Nishiyama, Shingo; Kakiuchi, Takeharu; Ito, Osamu; Tsukada, Hideo

doi:10.1186/s13550-018-0420-6

Cited by 6 publications

(2 citation statements)

References 31 publications

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“…Ceramides were reported to trigger redox signaling and activate reactive oxygen species (ROS) generating enzymes in NASH [26, 31, 32]. In our study, we found that ceramide inhibition could restore the expression of genes associated with fatty acid oxidation that was previously impaired due to ROS injury and mitochondrial dysfunction in NASH.…”

Section: Discussionsupporting

confidence: 52%

Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis

et al. 2019

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BackgroundCeramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy.MethodsSprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days for 8 weeks) (n = 10). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB).ResultsMyriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including Fabp1, Pparα, Cpt-1α and Acox-2. Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB.ConclusionsCeramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH.Trial registrationRegistration ID: ChiCTR-DDT-13003983. Data of registration: 13 May, 2013, retrospectively registered.

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Section: Discussionsupporting

confidence: 52%

Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis

et al. 2019

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“…Some target α v β 3 expressing stellate cells 29 or type I collagen 30 for the identification of early or late fibrosis. Radiotracers targeting at liver metabolism, including mitochondria, have also been evaluated, often leading to a decrease in liver uptake during NASH 31 . Inflammation imaging has been evaluated using nanobody derived radiotracers targeting at Kupffer cells in a mouse MCD model of NASH 32 .…”

Section: Discussionmentioning

confidence: 99%

Molecular imaging of liver inflammation using an anti-VCAM-1 nanobody

et al. 2023

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To date, a biopsy is mandatory to evaluate parenchymal inflammation in the liver. Here, we evaluated whether molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) could be used as an alternative non-invasive tool to detect liver inflammation in the setting of chronic liver disease. To do so, we radiolabeled anti-VCAM-1 nanobody (99mTc-cAbVCAM1-5) and used single-photon emission computed tomography (SPECT) to quantify liver uptake in preclinical models of non-alcoholic fatty liver disease (NAFLD) with various degree of liver inflammation: wild-type mice fed a normal or high-fat diet (HFD), FOZ fed a HFD and C57BL6/J fed a choline-deficient or -supplemented HFD. 99mTc-cAbVCAM1-5 uptake strongly correlates with liver histological inflammatory score and with molecular inflammatory markers. The diagnostic power to detect any degree of liver inflammation is excellent (AUROC 0.85–0.99). These data build the rationale to investigate 99mTc-cAbVCAM1-5 imaging to detect liver inflammation in patients with NAFLD, a largely unmet medical need.

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Advancements of non‐invasive imaging technologies for the diagnosis and staging of liver fibrosis: Present and future

Huang,

Peng,

Kang

2024

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Liver fibrosis is a reparative response triggered by liver injury. Non‐invasive assessment and staging of liver fibrosis in patients with chronic liver disease are of paramount importance, as treatment strategies and prognoses depend significantly on the degree of fibrosis. Although liver fibrosis has traditionally been staged through invasive liver biopsy, this method is prone to sampling errors, particularly when biopsy sizes are inadequate. Consequently, there is an urgent clinical need for an alternative to biopsy, one that ensures precise, sensitive, and non‐invasive diagnosis and staging of liver fibrosis. Non‐invasive imaging assessments have assumed a pivotal role in clinical practice, enjoying growing popularity and acceptance due to their potential for diagnosing, staging, and monitoring liver fibrosis. In this comprehensive review, we first delved into the current landscape of non‐invasive imaging technologies, assessing their accuracy and the transformative impact they have had on the diagnosis and management of liver fibrosis in both clinical practice and animal models. Additionally, we provided an in‐depth exploration of recent advancements in ultrasound imaging, computed tomography imaging, magnetic resonance imaging, nuclear medicine imaging, radiomics, and artificial intelligence within the field of liver fibrosis research. We summarized the key concepts, advantages, limitations, and diagnostic performance of each technique. Finally, we discussed the challenges associated with clinical implementation and offer our perspective on advancing the field, hoping to provide alternative directions for the future research.

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Sensitive and early detection of mitochondrial dysfunction in the liver of NASH model mice by PET imaging with 18F-BCPP-BF

Cited by 6 publications

References 31 publications

Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis

Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis

Molecular imaging of liver inflammation using an anti-VCAM-1 nanobody

Advancements of non‐invasive imaging technologies for the diagnosis and staging of liver fibrosis: Present and future

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