Truong 2020 Cytokine
Truong NTT, Lydic TA, Bazil JN, Suryadevara A, Olson LK (2020) Regulation of lipid metabolism in pancreatic beta cells by interferon gamma: a link to anti-viral function. Cytokine 133:155147. |
Truong NTT, Lydic TA, Bazil JN, Suryadevara A, Olson LK (2020) Cytokine
Abstract: Interferons (IFN) have been shown to alter lipid metabolism in immune and some non-hematopoietic cells and this affects host cell response to pathogens. In type 1 diabetes, IFNΞ³ acts as a proinflammatory cytokine that, along with other cytokines, is released during pancreatic beta cell autoinflammation and contributes to immune response and beta cell dysfunction. The hypothesis tested herein is that IFN modifies beta cell lipid metabolism and this is associated with enhanced anti-viral response and beta cell stress. Treatment of INS-1 cells with IFNΞ³ for 6 to 24 h led to a dynamic change in TAG and lipid droplet (LD) levels, with a decrease at 6 h and an increase at 24 h. The later accumulation of TAG was associated with increased de novo lipogenesis (DNL), and impaired mitochondrial fatty acid oxidation (FAO). Gene expression results suggested that IFNΞ³ regulates lipolytic, lipogenic, LD and FAO genes in a temporal manner. The changes in lipid gene expression are dependent on the classical Janus kinase (JAK) pathway. Pretreatment with IFNΞ³ robustly enhanced anti-viral gene expression induced by the viral mimetic polyinosinic: polycytidylic acid (PIC), and this potentiating effect of IFNΞ³ was markedly attenuated by inhibitors of DNL. The IFNΞ³-induced accumulation of lipid, however, was insufficient to cause endoplasmic reticulum (ER) stress. These studies demonstrated a non-canonical effect of IFNΞ³ in regulation of pancreatic beta cell lipid metabolism that is intimately linked with host cell defense and might alter cellular function early in the progression to type 1 diabetes. β’ Keywords: Anti-viral, Interferon gamma, Lipid metabolism, Pancreatic beta cell, Type 1 diabetes β’ Bioblast editor: Plangger M β’ O2k-Network Lab: US MI East Lansing Bazil JN
Labels: MiParea: Respiration
Organism: Rat
Tissue;cell: Islet cell;pancreas;thymus
Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET
HRR: Oxygraph-2k
2020-06