This review shows conclusively that profens can enter physiological pathways of lipid biochemistry. The first step in this interaction is the formation of an acyl-CoA thioester. These conjugates can lead to the incorporation of the xenobiotic acid into lipids. The resulting hybrid triglycerides have the potential to form long-lasting residues in adipose tissues and to be incorporated into membranes. Furthermore, the acyl-CoA conjugate may also alter lipid biochemistry by inhibiting lipid beta-oxidation either by interfering with the acyl-CoA synthetases or by modifying CoA levels. Thus, the acyl-CoA conjugates of profens intermediates in the inversion of inactive (R)-profens to active (S)-profens can be viewed as pivotal to bioactivation and to pathways of potential toxicity.
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Genet Med
January 2025
Lipids and Atherosclerosis Laboratory, Department of Medicine and Dermatology, Centro de Investigaciones Médico Sanitarias (CIMES), Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA -Plataforma Bionand), University of Málaga, Málaga, Spain; Lipid Unit. Internal Medicine Service. University Hospital Virgen de la Victoria, Málaga, Spain.
Purpose: Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases.
Methods: 245 patients with severe hypertriglyceridemia underwent next-generation sequencing.
Life Metab
December 2024
Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease that can progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and cancer. The zonal distribution of biomolecules in the liver is implicated in mediating the disease progression. Recently, G-protein-coupled receptor 35 (GPR35) has been highlighted to play a role in MASLD, but the precise mechanism is not fully understood, particularly, in a liver-zonal manner.
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April 2024
Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China.
In addition to their pivotal roles in energy storage and expenditure, adipose tissues play a crucial part in the secretion of bioactive molecules, including peptides, lipids, metabolites, and extracellular vesicles, in response to physiological stimulation and metabolic stress. These secretory factors, through autocrine and paracrine mechanisms, regulate various processes within adipose tissues. These processes include adipogenesis, glucose and lipid metabolism, inflammation, and adaptive thermogenesis, all of which are essential for the maintenance of the balance and functionality of the adipose tissue micro-environment.
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October 2024
CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai 200031, China.
Dyslipidemia affects approximately half of all people with gout, and prior Mendelian randomization analysis suggested a causal role for elevated triglycerides in hyperuricemia (HU), but the underlying mechanisms remain elusive. We hypothesize that dyslipidemia promotes hepatic urate biosynthesis in HU and gout and fatty acid (FA) oxidation (FAO) drives this process. Here we developed a targeted metabolomics to quantify major metabolites in purine metabolic pathway in the sera of a human cohort with HU, gout, and normaluricemic controls.
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December 2022
State Key Laboratory of Molecular Biology, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
As an essential part of adaptive immunity, T cells coordinate the immune responses against pathogens and cancer cells. Lipid metabolism has emerged as a key regulator for the activation, differentiation, and effector functions of T cells. Therefore, uncovering the molecular mechanisms by which lipid metabolism dictates T cell biology is of vital importance.
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