Effects of FABP knockdown on flight performance of the desert locust, Schistocerca gregaria.

During migratory flight, desert locusts rely on fatty acids as their predominant source of energy. Lipids mobilized in the fat body are transported to the flight muscles and enter the muscle cells as free fatty acids. It has been postulated that muscle fatty acid binding protein (FABP) is needed for the efficient translocation of fatty acids through the aqueous cytosol towards mitochondrial ß-oxidation. To assess whether FABP is required for this process, dsRNA was injected into freshly emerged adult males to knock down the expression of FABP. Three weeks after injection, FABP and its mRNA were undetectable in flight muscle, indicating efficient silencing of FABP expression. At rest, control and treated animals exhibited no morphological or behavioral differences. In tethered flight experiments, both control and treated insects were able to fly continually in the initial, carbohydrate-fueled phase of flight, and in both groups, lipids were mobilized and released into the hemolymph. Flight periods exceeding 30 min, however, when fatty acids become the main energy source, were rarely possible for FABP-depleted animals, while control insects continued to fly for more than 2 h. These results demonstrate that FABP is an essential element of skeletal muscle energy metabolism in vivo.

Understanding AMD by analogy: systematic review of lipid-related common pathogenic mechanisms in AMD, AD, AS and GN.

RATIONALE: Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly. Due to its complex etiology, current treatments have been insufficient. Previous studies reveal three systems closely involved in AMD pathogenesis: lipid metabolism, oxidation and inflammation. These systems are also involved in Alzheimer's disease, atherosclerosis and glomerulonephritis. Understanding commonalities of these four diseases may provide insight into AMD etiology. OBJECTIVES: To understand AMD pathogenesis by analogy and suggest ideas for future research, this study summarizes main commonalities in disease pathogenesis of AMD, Alzheimer's disease, atherosclerosis and glomerulonephritis. METHODS: Articles were identified through PubMed, Ovid Medline and Google Scholar. We summarized the common findings and synthesized critical differences. RESULTS: Oxidation, lipid deposition, complement activation, and macrophage recruitment are involved in all four diseases shown by genetic, molecular, animal and human studies. Shared genetic variations further strengthen their connection. Potential areas for future research are suggested throughout the review. CONCLUSIONS: The four diseases share many steps of an overall framework of pathogenesis. Various oxidative sources cause oxidative stress. Oxidized lipids and related molecules accumulate and lead to complement activation, macrophage recruitment and pathology. Investigations that arise under this structure may aid us to better understand AMD pathology.

The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity.

Activation of the innate immune response triggered by dsRNA viruses occurs through the assembly of the Mitochondrial Anti-Viral Signaling (MAVS) complex. Upon recognition of viral dsRNA, the cytosolic receptor RIG-I is activated and recruited to MAVS to activate the immune signaling response. We here demonstrate a strict requirement for a mitochondrial anchored protein ligase, MAPL (also called MUL1) in the signaling events that drive the transcriptional activation of antiviral genes downstream of Sendai virus infection, both in vivo and in vitro. A biotin environment scan of MAPL interacting polypeptides identified a series of proteins specific to Sendai virus infection; including RIG-I, IFIT1, IFIT2, HERC5 and others. Upon infection, RIG-I is SUMOylated in a MAPL-dependent manner, a conjugation step that is required for its activation. Consistent with this, MAPL was not required for signaling downstream of a constitutively activated form of RIG-I. These data highlight a critical role for MAPL and mitochondrial SUMOylation in the early steps of antiviral signaling.