Role of Nonesterified Fatty Acids in Necrotizing Pancreatitis: An In Vivo Experimental Study in Rats

Paye, François; Presset, Olivier; Chariot, J; Molas, G; Rozé, C

doi:10.1097/00006676-200111000-00002

Cited by 7 publications

(2 citation statements)

References 35 publications

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“…These data also reveal an increase of OA and PA concentrations in diabetic compared to healthy individuals of approximately 10% [36]. Serum concentrations of rodents are lower with a total FFA serum concentration of 0.8-1.5 mM [39,40]. Authors claim that a FFA concentration range of 0.5-2.0 mM is suitable to mimic lipotoxicity in T2DM [41,42].…”

Section: Factors Influencing Lipotoxic Outcomes In Tissue Culturementioning

confidence: 89%

Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review

2021

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Lipotoxicity is a major contributor to type 2 diabetes mainly promoting mitochondrial dysfunction. Lipotoxic stress is mediated by elevated levels of free fatty acids through various mechanisms and pathways. Impaired peroxisome proliferator-activated receptor (PPAR) signaling, enhanced oxidative stress levels, and uncoupling of the respiratory chain result in ATP deficiency, while β-cell viability can be severely impaired by lipotoxic modulation of PI3K/Akt and mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) pathways. However, fatty acids are physiologically required for an unimpaired β-cell function. Thus, preparation, concentration, and treatment duration determine whether the outcome is beneficial or detrimental when fatty acids are employed in experimental setups. Further, ageing is a crucial contributor to β-cell decay. Cellular senescence is connected to loss of function in β-cells and can further be promoted by lipotoxicity. The potential benefit of nutrients has been broadly investigated, and particularly polyphenols were shown to be protective against both lipotoxicity and cellular senescence, maintaining the physiology of β-cells. Positive effects on blood glucose regulation, mitigation of oxidative stress by radical scavenging properties or regulation of antioxidative enzymes, and modulation of apoptotic factors were reported. This review summarizes the significance of lipotoxicity and cellular senescence for mitochondrial dysfunction in the pancreatic β-cell and outlines potential beneficial effects of plantbased nutrients by the example of polyphenols.

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Section: Factors Influencing Lipotoxic Outcomes In Tissue Culturementioning

confidence: 89%

Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review

2021

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“…Previously, THL has been investigated in vivo for the treatment of pancreatitis by intravenous, intraperitoneal, − and direct injection into pancreatic tissue. − In addition, THL has been found to inhibit the thioesterase domain of fatty acid synthase (FAS) ,, and has been investigated as anticancer chemotherapy. − THL has been shown to inhibit the in vitro growth of Giardia duodenalis, a gastrointestinal parasite . THL may also have value as an antifungal agent against fungi that lack lipase enzymes and rely on free fatty acids for their nutrition and growth. , …”

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confidence: 99%

Stereochemical Structure Activity Relationship Studies (S-SAR) of Tetrahydrolipstatin

Liu

Wang

Duclos

et al. 2018

ACS Med. Chem. Lett.

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Tetrahydrolipstatin (THL), its enantiomer, and an additional six diastereomers were evaluated as inhibitors of the hydrolysis of -nitrophenyl butyrate by porcine pancreatic lipase. ICs were found for all eight stereoisomers ranging from a low of 4.0 nM for THL to a high of 930 nM for the diastereomer with the inverted stereocenters at the 2,3,2'-positions. While the enantiomer of THL was also significantly less active (77 nM) the remaining five stereoisomers retained significant inhibitory activities (ICs = 8.0 to 20 nM). All eight compounds were also evaluated against three human cancer cell lines (human breast cancers MCF-7 and MDA-MB-231, human large-cell lung carcinoma H460). No appreciable cytotoxicity was observed for THL and its seven diastereomers, as their ICs in a MTT cytotoxicity assay were all greater than 3 orders of magnitude of camptothecin.

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