Publications by authors named "L Cheval"

Plasma growth differentiation factor-15 (GDF-15) levels increase with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) but the underlying mechanism remains poorly defined. Using male mouse models of obesity and MASLD, and biopsies from carefully-characterized patients regarding obesity, type 2 diabetes (T2D) and MASLD status, we identify adipose tissue (AT) as the key source of GDF-15 at onset of obesity and T2D, followed by liver during the progression towards metabolic dysfunction-associated steatohepatitis (MASH). Obesity and T2D increase GDF15 expression in AT through the accumulation of macrophages, which are the main immune cells expressing GDF15.

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A detailed knowledge of the lipid composition of components of nephrons is crucial for understanding physiological processes and the development of kidney diseases. However, the lipidomic composition of kidney tubular segments is unknown. We manually isolated the proximal convoluted tubule (PCT), the cortical thick ascending limb of Henle's loop, and the cortical collecting duct from 5 lean and obese mice and subjected the samples to shotgun lipidomics analysis by high-resolution mass spectrometry acquisition.

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Long-chain acyl-CoA synthetase family 4 (ACSL4) metabolizes long-chain polyunsaturated fatty acids (PUFAs), enriching cell membranes with phospholipids susceptible to peroxidation and drive ferroptosis. The role of ACSL4 and ferroptosis upon endoplasmic-reticulum (ER)-stress-induced acute kidney injury (AKI) is unknown. We used lipidomic, molecular, and cellular biology approaches along with a mouse model of AKI induced by ER stress to investigate the role of ACSL4 regulation in membrane lipidome remodeling in the injured tubular epithelium.

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Article Synopsis
  • - Lithium exposure can lead to nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), but this study shows that low levels of lithium can prevent NDI while not impacting kidney tubule damage.
  • - In an experiment with rats over 6 months, those exposed to low lithium concentrations showed no signs of NDI but still had microcystic dilations in kidney tubules, particularly in collecting ducts (CDs).
  • - The research identified differences in the cellular make-up of hypertrophied and microcystic CDs, suggesting that they may be caused by different mechanisms, and additional treatment with amiloride didn’t lead to significant changes in kidney structure.
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Article Synopsis
  • Genetic differences exist between the medullary (MTAL) and cortical (CTAL) thick ascending limbs of the loop of Henle, notably with higher claudin-10 expression in MTAL.
  • A study using RNA sequencing revealed 637 genes were differentially expressed in MTAL compared to 76 in CTAL when comparing wild type (WT) and claudin-10 knockout (cKO) mice.
  • Gene expression analysis showed significant clustering differences between WT MTAL and other replicates, with cKO samples enriched for specific mRNAs linked to calcium and vitamin D pathways, which are important for divalent cation reabsorption.
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