Role of adipose tissue in methionine-choline-deficient model of non-alcoholic steatohepatitis (NASH).

UNLABELLED: Methionine-choline-deficient (MCD) diet is a widely used dietary model of non-alcoholic steatohepatitis (NASH) in rodents. However, the contribution of adipose tissue to MCD-induced steatosis, and inflammation as features of NASH are not fully understood. The goal of this study was to elucidate the role of adipose tissue fatty acid (FA) metabolism, adipogenesis, lipolysis, inflammation and subsequent changes in FA profiles in serum and liver in the pathogenesis of steatohepatitis. We therefore fed ob/ob mice with control or MCD diet for 5 weeks. MCD-feeding increased adipose triglyceride lipase and hormone sensitive lipase activities in all adipose depots which may be attributed to increased systemic FGF21 levels. The highest lipase enzyme activity was exhibited by visceral WAT. Non-esterified fatty acid (NEFA)-18:2n6 was the predominantly elevated FA species in serum and liver of MCD-fed ob/ob mice, while overall serum total fatty acid (TFA) composition was reduced. In contrast, an overall increase of all FA species from TFA pool was found in liver, reflecting the combined effects of increased FA flux to liver, decreased FA oxidation and decrease in lipase activity in liver. NAFLD activity score was increased in liver, while WAT showed no changes and BAT showed even reduced inflammation. CONCLUSION: This study demonstrates a key role for adipose tissue lipases in the pathogenesis of NASH and provides a comprehensive lipidomic profiling of NEFA and TFA homeostasis in serum and liver. Our findings provide novel mechanistic insights for the role of WAT in progression of MCD-induced liver injury.

A comprehensive method for lipid profiling by liquid chromatography-ion cyclotron resonance mass spectrometry.

This work aims to combine chromatographic retention, high mass resolution and accuracy, MS/MS spectra, and a package for automated identification and quantitation of lipid species in one platform for lipidomic analysis. The instrumental setup elaborated comprises reversed-phase HPLC coupled to a Fourier transform ion cyclotron resonance mass spectrometer (LTQ-FT), and Lipid Data Analyzer (LDA) software. Data analysis for lipid species quantification in this platform is based on retention time, mass resolution of 200,000, and mass accuracy below 2 ppm. In addition, automatically generated MS/MS spectra provide structural information at molecular level. This LC/MS technology allows analyzing complex biological samples in a quantitative manner as shown here paradigmatically for murine lipid droplets having a huge surplus of triacylglycerol species. Chromatographic preseparation of the bulk lipid class alleviates the problem of ion suppression of lipid species from other classes. Extension of 1D to 2D chromatography is possible, yet time consuming. The platform affords unambiguous detection of lipid species as low as 0.1‰ within major lipid classes. Taken together, a novel lipidomic LC/MS platform based on chromatographic retention, high mass resolution and accuracy, MS/MS analysis, and quantitation software enables analysis of complex samples as demonstrated for lipid droplets.

Characteristics of acute posttraumatic headache following mild head injury.

BACKGROUND: To examine the prevalence and characteristics of acute posttraumatic headache (APTH) attributed to mild head injury within a prospective, observational study design. METHODS: We recruited 100 patients with acute mild head injury as defined in the International Classification of Headache Disorders, 2nd Edition (ICHD-2) presenting to the department of trauma surgery at the Medical University of Vienna. Patients underwent a detailed telephone interview between days 7 and 10 and between days 90 and 100 after the injury. RESULTS: The prevalence of APTH was 66%. APTH had occurred within 24 hours after the trauma in 78% and lasted for a median of 3.0 days. Headache was unilateral in 45%. Aggravation by physical activity, nausea and photo-/phonophobia was present in 49%, 42% and 55%, respectively. The prevalence of APTH was related to conditions of chronic pain (excluding headache), pre-existing episodic headache, number of posttraumatic symptoms, anxiety and depression. At follow-up at 90-100 days, posttraumatic headache had abated in all patients. CONCLUSIONS: APTH attributed to mild head injury is a common but self-limiting condition frequently showing migrainous features. Participants with chronic pain other than headache, pre-existing headache and affective disorders are at higher risk of developing APTH. None of the patients developed chronic posttraumatic headache.