linoleic-acid and Fat-Necrosis

Acute lipolysis of visceral fat or circulating triglycerides may worsen acute pancreatitis (AP)-associated local and systemic injury. The pancreas expresses pancreatic triacylglycerol lipase (PNLIP), pancreatic lipase-related protein 2 (PNLIPRP2), and carboxyl ester lipase (CEL), which may leak into the visceral fat or systemic circulation during pancreatitis. We, thus, aimed to determine the pancreatic lipase(s) regulating lipotoxicity during AP. For this AP, associated fat necrosis was analyzed using Western blot analysis. Bile acid (using liquid chromatography-tandem mass spectrometry) and fatty acid (using gas chromatography) concentrations were measured in human fat necrosis. The fat necrosis milieu was simulated in vitro using glyceryl trilinoleate because linoleic acid is increased in fat necrosis. Bile acid requirements to effectively hydrolyze glyceryl trilinoleate were studied using exogenous or overexpressed lipases. The renal cell line (HEK 293) was used to study lipotoxic injury. Because dual pancreatic lipase knockouts are lethal, exocrine parotid acini lacking lipases were used to verify the results. PNLIP, PNLIPRP2, and CEL were increased in fat necrosis. Although PNLIP and PNLIPRP2 were equipotent in inducing lipolysis and lipotoxic injury, CEL required bile acid concentrations higher than in human fat necrosis. The high bile acid requirements for effective lipolysis make CEL an unlikely mediator of lipotoxic injury in AP. It remains to be explored whether PNLIP or PNLIPRP2 worsens AP severity in vivo.

Topics: Animals; Fat Necrosis; Gene Knockdown Techniques; HEK293 Cells; Humans; Intra-Abdominal Fat; Linoleic Acid; Lipase; Male; Mice; Pancreatitis

To evaluate the generation of halogenated fatty acids in the areas of fat necrosis during acute pancreatitis and to evaluate the effects of these molecules on the ensuing inflammatory process.. Lipid mediators derived from adipose tissue have been implicated in the progression of acute pancreatitis, although their precise role remains unknown.. Acute pancreatitis was induced in rats by intraductal infusion of 3.5% sodium taurocholate. Fatty acid chlorohydrins (FA-Cl) were measured in adipose tissue, ascitic fluid, and plasma by mass spectrometry. Chlorohydrins were also instilled in the rats' peritoneal cavity, and their effects on peritoneal macrophages activation and in systemic inflammation were evaluated. Finally, they have also been measured in plasma from human patients with acute pancreatitis.. Induced acute pancreatitis results in a substantial release not only of free fatty acids but also of the chlorohydrins of both oleic and linoleic acids from adipose tissue. In plasma, only the chlorohydrin of oleic acid was detected. Administration of 250-μM lipid chlorohydrins, which is the concentration found in ascitic fluid, induces the expression of TNFα and interleukin-1β in peritoneal macrophages and increases the systemic inflammatory response in pancreatitis. Finally, increased concentrations of oleic acid chlorohydrin have been found in plasma of human patients with pancreatitis.. During acute pancreatitis, adipose tissue release FA-Cl, which exacerbate the systemic inflammatory response.

Topics: Acute Disease; Animals; Biomarkers; Case-Control Studies; Chlorohydrins; Cholagogues and Choleretics; Chromatography, Liquid; Fat Necrosis; Gas Chromatography-Mass Spectrometry; Humans; Inflammation; Linoleic Acid; Macrophage Activation; Male; Mass Spectrometry; Oleic Acid; Pancreatitis; Peroxidase; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Taurocholic Acid