Downregulation of islet hormone-sensitive lipase during long-term high-fat feeding.
Lipid accumulation in pancreatic beta-cells during high-fat (HF) feeding may be involved in inducing a defective insulin secretion due to lipotoxicity. Hormone-sensitive lipase (HSL) is expressed and active in beta-cells, but its importance for islet dysfunction during the development of type 2 diabetes is not known. In this study, prolonged HF feeding of C57BL/6J mice, resulted in decreased HSL expression in islets, representing only 25+/-4% of the levels observed in controls. This was paralleled by triglyceride accumulation and blunted insulin secretion both in vivo and in vitro. After switching the HF diet to a LF diet, HSL expression increased 10-fold compared to the HF fed mice. This was accompanied by reduced triglyceride levels and a restored insulin secretion. These results support the notion that HSL plays a critical role in the regulation of intracellular triglyceride levels in beta-cells, and that downregulation of the enzyme may serve to protect against fatty acid-induced islet dysfunction.
Winzell
Maria Sörhede
MS
Department of Cell and Molecular Biology, Sec. for Molecular Signalling, Biomedical Center, Lund University, S-221 84, Lund, Sweden. Maria.Sorhede_Winzell@medkem.lu.se
Holm
Cecilia
C
Ahrén
Bo
B
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000378:metabolism; D018752:Diet, Fat-Restricted; D015536:Down-Regulation; D005223:Fats / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology; D002787:Sterol Esterase / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis
D005223:Fats; D007328:Insulin; D014280:Triglycerides; D002787:Sterol Esterase