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Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets.(More)
Lipid infusion or ingestion of a high-fat diet results in insulin resistance, but the mechanism underlying this phenomenon remains unclear. Here we show that, in rats fed a high-fat diet, whole-animal, muscle and liver insulin resistance is ameliorated following hepatic overexpression of malonyl-coenzyme A (CoA) decarboxylase (MCD), an enzyme that affects(More)
The structural integrity of mitochondrial cristae is crucial for mitochondrial functions; however, the molecular events controlling the structural integrity and biogenesis of mitochondrial cristae remain to be fully elucidated. Here, we report the functional characterization of a novel mitochondrial protein named CHCM1 (coiled coil helix cristae morphology(More)
Peroxisome proliferator-activated receptor-gamma co-activator 1alpha (PGC1alpha) is a promiscuous co-activator that plays a key role in regulating mitochondrial biogenesis and fuel homeostasis. Emergent evidence links decreased skeletal muscle PGC1alpha activity and coincident impairments in mitochondrial performance to the development of insulin resistance(More)
Deterioration of functional islet β-cell mass is the final step in progression to Type 2 diabetes. We previously reported that overexpression of Nkx6.1 in rat islets has the dual effects of enhancing glucose-stimulated insulin secretion (GSIS) and increasing β-cell replication. Here we show that Nkx6.1 strongly upregulates the prohormone VGF in rat islets(More)
The low-density lipoprotein receptor-related protein (LRP), a member of the low-density lipoprotein receptor gene family, mediates cellular signal transduction pathways. In this study we investigated the role of LRP in cell death. We found that incubation of mouse embryonic fibroblasts in serum-free media induces caspase-3 activation, an effect that is(More)
The ability to sense and adapt to hypoxic conditions plays a pivotal role in neuronal survival. Hypoxia induces the release of tissue-type plasminogen activator (tPA) from cerebral cortical neurons. We found that the release of neuronal tPA or treatment with recombinant tPA promotes cell survival in cerebral cortical neurons previously exposed to hypoxic(More)
The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect on brain injury after focal cerebral ischemia reperfusion, and to determine the possible mechanism. Behavioral tests were used to evaluate the damage to central nervous system. The infarct volume of brain was assessed in brain slices stained with 2%(More)
Microglia are the immune cells of the central nervous system (CNS) that become activated in response to pathological situations such as cerebral ischemia. Tissue-type plasminogen activator (tPA) is a serine proteinase that is found in the intravascular space and the CNS. The low-density lipoprotein receptor-related protein 1 (LRP1) is a member of the(More)
Tissue-type plasminogen activator (tPA) is found in the intravascular space and in the central nervous system. The low-density lipoprotein receptor-related protein (LRP) is expressed in neurons and in perivascular astrocytes. During cerebral ischemia, tPA induces the shedding of LRP's extracellular domain from perivascular astrocytes, and this is followed(More)