Mapping the triglyceride distribution in NAFLD human liver by MALDI imaging mass spectrometry reveals molecular differences in micro and macro steatosis

Alamri, Hussam; Patterson, Nathan Heath; Yang, Eun Jung; Zoroquiaín, Pablo; Lazaris, Anthoula; Chaurand, Pierre; Metrakos, Peter

doi:10.1007/s00216-018-1506-8

Cited by 33 publications

(36 citation statements)

References 37 publications

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“…As a cross-sectional correlative study, the direction of causality cannot be proven. Gas chromatography was used to separate and quantify FA, and quantification by mass spectrometry may be more sensitive and accurate ( 57 ). While the tissue samples studied were at least 1 cm 3 in volume, the lipid content of the liver is not homogeneous, and the distribution of FA differs within lipid droplets and outside of steatotic vesicles ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

The hepatic lipidome and HNF4α and SHBG expression in human liver

Winters

Scoggins

Appiah

et al. 2020

Endocrine Connections

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Low plasma levels of sex hormone binding globulin (SHBG) are a marker for obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The transcription factor HNF4α is a major determinant of hepatic SHBG expression and thereby serum SHBG levels, and mediates in part the association of low SHBG with hyperinsulinemia and hepatic steatosis. We analyzed the lipidome in human liver specimens from a cohort of patients who underwent hepatic resection as a treatment for cancer, providing insight into hepatic lipids in those without extreme obesity or the clinical diagnosis of NAFLD or non-alcoholic steatohepatitis. Both steatosis and high HOMA-IR were associated with higher levels of saturated and unsaturated FA, other than arachidonic, with the most dramatic rise in 18:1 oleate, consistent with increased stearoyl-Co A desaturase activity. Individuals with low HOMA-IR had low levels of total hepatic fatty acids while both low and high fatty acid levels characterized the high HOMA-IR group. Both insulin resistance and high levels of hepatic fat were associated with low expression levels of HNF4α and thereby SHBG, but expression of these genes was also low in the absence of these determinants, implying additional regulatory mechanisms that remain to be determined.

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Section: Discussionmentioning

confidence: 99%

The hepatic lipidome and HNF4α and SHBG expression in human liver

Winters

Scoggins

Appiah

et al. 2020

Endocrine Connections

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“…It describes a flexible method that can be easily modified by other research teams to suit their needs with no individual step requiring specialized equipment or instrumentation, thereby keeping costs to a minimum. Lipid-rich tissues such as the brain are particularly amenable to MALDI-IMS, but it is also amenable in organs where there is a pathological buildup of lipid such as atherosclerosis (Martin-Lorenzo, Alvarez-Llamas, McDonnell, & Vivanco, 2016), aneurysms (Tanaka et al, 2015), colon cancer (Hiraide et al, 2016), and nonalcoholic fatty liver disease (Alamri et al, 2018).…”

Section: Background Informationmentioning

confidence: 99%

Higher Mass Accuracy MALDI‐TOF/TOF Lipid Imaging of Human Brain Tissue in Alzheimer's Disease

O’Rourke

Smith

Sutherland

et al. 2019

CP Molecular Biology

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Matrix‐assisted laser desorption/ionization imaging mass spectrometry (MALDI‐IMS) is a well‐established technique for elucidating the location and relative abundance of a range of biomolecules. More recently, research into this technique has shifted from simple discovery and demonstration of utility to application in biomedical research. Here, we describe a protocol utilizing MALDI‐IMS for the spatial mapping of lipids in brain tissue from normal human brains and brains from patients with Alzheimer's disease, in the context of Alzheimer's disease. Improved accuracy calibration of the instrument from the tissue surface is emphasized, as this allows for significantly improved mass determination in time of flight (TOF)‐based instruments enabling more confident preliminary lipid identification. This improved initial result allows MALDI‐IMS data to be complemented with additional instrumentation, such as liquid chromatography mass spectrometry workflows or specialized non‐TOF systems such as Fourier transform cyclotron resonance instruments. This method is not limited to human tissue and can be applied to virtually any lipid‐rich formalin‐fixed tissue. © 2019 by John Wiley & Sons, Inc.

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“…To investigate NAFLD in terms of accumulated lipids, some visualisation methods of lipid droplets (LDs) were proposed, i.e., dye-based visualisation methods 4 , 5 , imaging mass spectrometry 6 , 7 and Raman microscopy 8 , 9 . Among these methods, Raman microscopy is a good candidate for the investigation of the accumulated lipids based on molecular species and structures of lipids.…”

Section: Introductionmentioning

confidence: 99%

Molecular imaging analysis of microvesicular and macrovesicular lipid droplets in non-alcoholic fatty liver disease by Raman microscopy

Minamikawa

Ichimura‐Shimizu

Takanari

et al. 2020

Sci Rep

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Predominant evidence of non-alcoholic fatty liver disease (NAFLD) is the accumulation of excess lipids in the liver. A small group with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH). However, there is a lack of investigation of the accumulated lipids with spatial and molecular information. Raman microscopy has the potential to characterise molecular species and structures of lipids based on molecular vibration and can achieve high spatial resolution at the organelle level. In this study, we aim to demonstrate the feasibility of Raman microscopy for the investigation of NAFLD based on the molecular features of accumulated lipids. By applying the Raman microscopy to the liver of the NASH model mice, we succeeded in visualising the distribution of lipid droplets (LDs) in hepatocytes. The detailed analysis of Raman spectra revealed the difference of molecular structural features of the LDs, such as the degree of saturation of lipids in the LDs. We also found that the inhomogeneous distribution of cholesterol in the LDs depending on the histology of lipid accumulation. We visualised and characterised the lipids of NASH model mice by Raman microscopy at organelle level. Our findings demonstrated that the Raman imaging analysis was feasible to characterise the NAFLD in terms of the molecular species and structures of lipids.

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Mapping the triglyceride distribution in NAFLD human liver by MALDI imaging mass spectrometry reveals molecular differences in micro and macro steatosis

Cited by 33 publications

References 37 publications

The hepatic lipidome and HNF4α and SHBG expression in human liver

The hepatic lipidome and HNF4α and SHBG expression in human liver

Higher Mass Accuracy MALDI‐TOF/TOF Lipid Imaging of Human Brain Tissue in Alzheimer's Disease

Molecular imaging analysis of microvesicular and macrovesicular lipid droplets in non-alcoholic fatty liver disease by Raman microscopy

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