Loss of Hepatic Leucine-Rich Repeat-Containing G-Protein Coupled Receptors 4 and 5 Promotes Nonalcoholic Fatty Liver Disease

Characterization of Triacylglycerol Estolide Isomers Using High-Resolution Tandem Mass Spectrometry with Nanoelectrospray Ionization

“…Ammonium formate and acetate are relatively volatile salts that are widely used in ESI and HPLC/MS. Ammonium adducts have been broadly adopted for the analysis neutral lipids, e.g., TGs [ 56 , 57 ], and they have also been utilized in the structural analysis of TG-ESTs [ 6 , 7 , 8 , 9 , 10 , 11 , 25 , 37 ]. Activation of these adducts typically leads to the neutral loss of ammonia, yielding product ions arising from proton transfer to the neutral lipid.…”

“…Triacylglycerol estolides (TG-ESTs) are a minor class of lipids consisting of a glycerol backbone to which a combination of fatty acids (FA) and estolides is esterified (also reported as fatty acid esters of hydroxy fatty acid, FAHFA, and ( O -acyl)-hydroxy fatty acid [ 1 , 2 , 3 ]) as a structural subunit [ 4 ]. TG-ESTs are biologically active molecules known from mammals [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ], plants [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], and fungi [ 29 , 33 , 39 , 40 , 41 ]. In mammalian TG-ESTs, a hydroxy fatty acid (HFA) is usually esterified with a non-hydroxy FA (“capped” estolide), while in plants and fungi, another HFA may be attached (“uncapped” estolide).…”

“…Reversed-phase HPLC makes it possible to separate TG-EST isomers according to the number of carbon atoms, carbon–carbon double bonds, and the estolide-branching site in the FAHFA subunit [ 7 ]. HPLC coupled with mass spectrometry (HPLC/MS) offers excellent sensitivity and selectivity for TG-EST in biological samples [ 6 , 7 , 8 , 9 , 10 , 11 , 25 ]. Electrospray ionization (ESI) of this lipid class typically generates ammonium [M + NH 4 ] + , sodium [M + Na] + , or lithium [M + Li] + molecular adducts depending on conditions, with subsequent ion activation by collision-induced dissociation (CID) or higher-energy collisional dissociation (HCD) generating structurally informative product ions [ 6 , 7 , 8 , 9 , 10 , 25 , 26 , 27 , 28 , 35 , 37 ].…”

“…HPLC coupled with mass spectrometry (HPLC/MS) offers excellent sensitivity and selectivity for TG-EST in biological samples [ 6 , 7 , 8 , 9 , 10 , 11 , 25 ]. Electrospray ionization (ESI) of this lipid class typically generates ammonium [M + NH 4 ] + , sodium [M + Na] + , or lithium [M + Li] + molecular adducts depending on conditions, with subsequent ion activation by collision-induced dissociation (CID) or higher-energy collisional dissociation (HCD) generating structurally informative product ions [ 6 , 7 , 8 , 9 , 10 , 25 , 26 , 27 , 28 , 35 , 37 ]. These spectra usually show product ions identifying the FA(s) linked to the glycerol backbone and the composition of the FAHFA subunit(s) [ 6 , 7 , 25 , 26 , 27 ].…”

Comparing rare variants versus common in the pathogenesis of nonalcoholic fatty liver disease: a whole exome sequencing approach

“…A study demonstrated that hepatic loss of Wnt/beta-catenin activity by deletion of LGR4 led to loss of bile acid secretion, altered lipid homeostasis, and deregulation of lipoprotein pathways contributing to the onset of NAFLD in an animal model. 24 There is only one study that evaluated the genetic susceptibility for NAFLD at the genome wide level in the Indian ethnicity to the best of our knowledge. The study carried out by two Institutes from India, namely, Population Health and Research Institute (PHRI) and Holistic Health and Research Institute, apart from collaborators from United Kingdom consisted of the Trivandrum population-based NAFLD cohort.…”