Publications by authors named "P Rada"

Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE).

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Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss.

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Article Synopsis
  • The study investigates the role of protein kinase D2 (PKD2) in regulating insulin signaling and metabolic homeostasis in the liver, as its functions are not yet fully understood.
  • Using various experimental methods, including PKD2 overexpression and specific gene depletion in mouse models, researchers assessed how PKD2 affects insulin responses and glucose metabolism.
  • Findings reveal that PKD2 inhibits insulin signaling by modifying the phosphorylation of insulin receptor substrate 1 (IRS1), and suggest that PKD2 could be targeted therapeutically to combat hepatic insulin resistance.
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The role of peroxisome proliferator-activated receptor (PPAR)β/δ in hepatic fibrosis remains a subject of debate. Here, we examined the effects of a PPARβ/δ agonist on the pathogenesis of liver fibrosis and the activation of hepatic stellate cells (HSCs), the main effector cells in liver fibrosis, in response to the pro-fibrotic stimulus transforming growth factor-β (TGF-β). The PPARβ/δ agonist GW501516 completely prevented glucose intolerance and peripheral insulin resistance, blocked the accumulation of collagen in the liver, and attenuated the expression of inflammatory and fibrogenic genes in mice fed a choline-deficient high-fat diet (CD-HFD).

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Article Synopsis
  • Hydrogenosomes, found in anaerobic organisms like the parasite Trichomonas vaginalis, have specialized functions due to limited oxygen, leading to unique mechanisms for protein import that differ from typical mitochondria.
  • The study identifies a hybrid translocase complex (TvTIM) combining features of TIM22 and TIM23, which facilitates the import of specific proteins into the hydrogenosomal matrix.
  • The research highlights the unique structural features and protein associations of TvTIM, revealing significant differences in how these organelles function compared to traditional mitochondria.
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