Biology subjects

Zuellig, T.

Publications and source records attributed to Zuellig, T..

2 recordsLinked to original sources

bioRxiv2026

Triacylglycerol fatty acid composition modulates ATGL regioselectivity and diacylglycerol output

Adipose triglyceride lipase (ATGL) catalyses the first and rate-limiting step of intracellular triacylglycerol (TAG) hydrolysis, yielding diacylglycerol (DAG) and a free fatty acid (FA). The site of TAG cleavage determines the regioisomeric identity of the DAG product, with distinct consequences for downstream signalling and lipid metabolism. Here, we show that ATGL prefers specific fatty acyl chain lengths and that this preference contributes to its regioselectivity on heterogeneous TAG substrates. Structural modelling identified a substrate-binding pocket comprising a hydrophilic anchor and a hydrophobic tunnel whose dimensions favour long-chain FAs. Mass spectrometry-based analysis of DAG products generated by ATGL from defined TAG substrates revealed an intrinsic preference for terminal (sn-1/sn-3) ester bond cleavage. Acyl-chain compatibility modulated this preference, with poorly accommodated terminal chains increasing the relative contribution of sn-2 cleavage. Consequently, ATGL generated predominantly sn-2-retaining DAG species from heterogeneous TAG substrates containing long-chain fatty acyl chains, including substantial amounts of the sn-1,2-DAG regioisomer, which has not previously been associated with ATGL activity. These findings link the fatty acyl chain composition of TAGs to the DAG regioisomer profile generated by ATGL-mediated lipolysis and provide substrate-dependent parameters for more species-resolved models of lipid metabolism.

biochemistry↗

bioRxiv2024

Urinary multi-omics reveal non-invasive diagnostic biomarkers in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the kidney malignancy with the highest incidence and mortality rates. Despite the high patient burden, there are no biomarkers for rapid diagnosis and public health surveillance. Urine would be an ideal source of ccRCC biomarkers due to the low invasiveness, easy accessibility, and the kidneys intrinsic role in filtering urine. In the present work, by combining proteomics, lipidomics and metabolomics, we detected urogenital metabolic dysregulation in ccRCC patients with increased lipid metabolism, altered mitochondrial respiration signatures and increased urinary lipid content. Importantly, we identify three early-stage diagnostic biomarkers for ccRCC in urine samples: Serum amyloid A1 (SAA1), Haptoglobin (HP) and Lipocalin 15 (LCN15). We further implemented a parallel reaction monitoring mass spectrometry protocol for rapid and sensitive detection of SAA1, HP and LCN15 and combined all three proteins into a diagnostic UrineScore. In our discovery cohort, this score had a performance accuracy of 96% in receiver operating characteristic curve (ROC) analysis for classification of ccRCC versus control cases. Our data identifies tractable and highly efficacious urinary biomarkers for ccRCC diagnosis and serve as a first step towards the development of more rapid and accessible urinary diagnostic platforms.

cancer biology↗