Biology subjects

Lamers, W. H.

Publications and source records attributed to Lamers, W. H..

3 recordsLinked to original sources

bioRxiv2025

The Diabetes Gene Tcf7l2 Organizes Gene Expression in the Liver and Regulates Amino Acid Metabolism

TCF7L2 harbors the strongest genetic association with diabetes identified thus far. However, its function in liver has remained unclear. Here, we find using mice with liver-specific deletion, that Tcf7l2 plays a central role in maintaining hepatic zonation. That is, in the normal liver, many genes show gradients of expression across the liver lobule; in the absence of Tcf7l2, these gradients collapse. One major consequence is the disorganization of glutamine metabolism, with a loss of the glutamine production program, ectopic expression of the glutamine consumption program, and a decrease in glutamine levels. In parallel, metabolomic profiling shows glutamine to be the most significantly decreased metabolite in individuals harboring the rs7903146 variant in TCF7L2. Taken together, these data indicate that hepatic TCF7L2 has a secondary role in glycemic control, but a primary role in maintaining transcriptional architecture and glutamine homeostasis.

physiology↗

bioRxiv2021

Evidence for glutamine synthetase function in mouse spinal cord oligodendrocytes

Glutamine synthetase (GS) is a key enzyme that metabolizes glutamate into glutamine. While GS is expressed by astrocytes of the central nervous system (CNS), expression in other glial lineages has been noted. Using a combination of reporter mice and cell typespecific markers, we show that GS is expressed in myelinating oligodendrocytes (OL) but not oligodendrocyte progenitor cells (OPC) of the mouse spinal cord abutting ventral horn motor neurons. To investigate the role of GS in mature OL, we used a conditional knockout (cKO) approach to selectively delete GS-encoding gene (Glul) in OL, which caused a significant decrease in glutamine levels on spinal cord extracts. We evaluated the effect on ventral spinal cord sensorimotor circuits and observed that GS cKO mice (CNP-cre+: Glulfl/fl) showed no differences in motor neuron numbers, size or axon density; OL differentiation and myelination in the ventral spinal cord at 1- and 6-months of age was normal. Interestingly, GS cKO mice showed an early and specific decrease in peak force while motor function remained otherwise unaffected. These findings provide evidence OL-encoded GS functions in spinal cord sensorimotor circuit. Main pointsO_LIGlutamine synthetase (GS) is highly expressed in oligodendrocytes (OL) of the mouse spinal cord. C_LIO_LIOL-specific GS loss of function causes transient decrease in peak force, but other substantial neurological dysfunction was not detected. C_LI

neuroscience↗

bioRxiv2019

Pseudolesion in the right parafissural liver parenchyma on CT: the base is found in embryology and collagen content.

BackgroundComputed tomography (CT) images of livers may show a hypo-attenuated structure alongside the falciform ligament, which can be a focal fatty pseudolesion and can mimic a malignancy. The preferred location is on the right parafissural site, ventral in segment IVa/b. The etiology is not clear, nor is it known how the histology of this location develops. These are evaluated in this study.\n\nMethods40 adult cadavers with autopsy and / or postmortem CT in a university hospital and a forensic center were included. Liver biopsies were taken at the left side of the falciform ligament as control, and at the right side as the possible precursor of a pseudolesion; these were examined for collagen and fat content. Cadavers with steatotic (>5% fat) or fibrotic (>2% collagen) control samples were excluded.\n\nResultsSignificantly more collagen was present in the right parafissural liver parenchyma: median 0.68% (IQR: 0.32 - 1.17%), compared to the left side 0.48% (IQR: 0.21 - 0.75%) (p 0.008), with equal fat content and CT attenuation values. The etiophysiology goes back to the demise of the umbilical venes in the early embryonic and neonatal period.\n\nConclusionsThe right parafissural area contains more collagen and an equal amount of fat compared to the control left side. This supports the hypothesis of delayed, third inflow: the postnatal change in blood supply from umbilical to portal leaves the downstream parafissural area hypoperfused leading to hypoxia which in turn results in collagen accumulation and the persistence of paraumbilical veins of Sappey.\n\nKey pointsO_LIThe typical location for a parafissural hepatic pseudolesion contains increased collagen.\nC_LIO_LIA change in histology is caused by physiological demise of the umbilical venes.\nC_LIO_LIThe suboptimal blood supply of the right parafissural side leads to hypoxia and collagen deposition.\nC_LIO_LIEmbryologic knowledge and postmortem histology can help resolve issues in radiology.\nC_LI

physiology↗