1.Glutamine Modulates Macrophage Lipotoxicity.
He L1,2, Weber KJ3,4, Schilling JD5,6,7. Nutrients. 2016 Apr 12;8(4). pii: E215.
Obesity and diabetes are associated with excessive inflammation and impaired wound healing. Increasing evidence suggests that macrophage dysfunction is responsible for these inflammatory defects. In the setting of excess nutrients, particularly dietary saturated fatty acids (SFAs), activated macrophages develop lysosome dysfunction, which triggers activation of the NLRP3 inflammasome and cell death. The molecular pathways that connect lipid stress to lysosome pathology are not well understood, but may represent a viable target for therapy. Glutamine uptake is increased in activated macrophages leading us to hypothesize that in the context of excess lipids glutamine metabolism could overwhelm the mitochondria and promote the accumulation of toxic metabolites. To investigate this question we assessed macrophage lipotoxicity in the absence of glutamine using LPS-activated peritoneal macrophages exposed to the SFA palmitate. We found that glutamine deficiency reduced lipid induced lysosome dysfunction, inflammasome activation, and cell death.
2.Molecular Characterization of a Novel Germline VHL Mutation by Extensive In Silico Analysis in an Indian Family with Von Hippel-Lindau Disease.
Arunachal G1, Pachat D1, Doss CG2, Danda S1, Pai R3, Ebenazer A3. Genet Res Int. 2016;2016:9872594. doi: 10.1155/2016/9872594. Epub 2016 Mar 16.
Von Hippel-Lindau [VHL] disease, an autosomal dominant hereditary cancer syndrome, is well known for its complex genotype-phenotype correlations. We looked for germline mutations in the VHL gene in an affected multiplex family with Type 1 VHL disease. Real-Time quantitative PCR for deletions and Sanger sequencing of coding regions along with flanking intronic regions were performed in two affected individuals and one related individual. Direct sequencing identified a novel heterozygous single nucleotide base substitution in both the affected members tested, segregating with VHL phenotype in this family. This variant in exon 3, c.473T>A, results in substitution of leucine, a highly conserved acid, to glutamine at position 158 [p.L158Q] and has not been reported thus far as a variant associated with disease causation. Further, this variant was not observed in 50 age and ethnicity matched healthy individuals. Extensive in silico prediction analysis along with molecular dynamics simulation revealed significant deleterious nature of the substitution L158Q on pVHL.
3.Age and High-Fat Diet Effects on Glutamine Synthetase Immunoreactivity in Liver and Hippocampus and Recognition Memory in Mice.
Soontornniyomkij V1, Kesby JP, Soontornniyomkij B, Kim JJ, Kisseleva T, Achim CL, Semenova S, Jeste DV. Curr Aging Sci. 2016 Apr 13. [Epub ahead of print]
BACKGROUND: High-fat diet (HFD)-induced obesity may promote age-related memory impairment via disturbances of ammonia-glutamine metabolism.
4.Glycoholics Anonymous: Cancer Sobers Up with mTORC1.
Fu V1, Moroishi T1, Guan KL2. Cancer Cell. 2016 Apr 11;29(4):432-4. doi: 10.1016/j.ccell.2016.03.016.
In this issue of Cancer Cell, Pusapati et al. (2016) reveal that mTORC1 orchestrates the metabolic reprogramming of cancer cells in response to glycolytic inhibitors, bypassing glycolysis by increasing glutamine uptake and pentose phosphate flux to generate energy and biomass.