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High intrahepatic lipid content is associated with low choline status in humans-a 1H-MRS study at 3 Tesla1Department of Radiology, Maastricht University Medical Centre, Mastricht, Netherlands, 2Nutrition and Movement Sciences, NUTRIM school for Nutrition and Translational Research in Metabolism, Maastricht, Netherlands
Synopsis
Non-alcoholic fatty liver (NAFL) has become a major threat to metabolic health. Animal studies have suggested that disturbances in choline metabolism may be linked to the development of NAFL. However, to date, human data on the link of choline and NAFL is scarce. The trimethylammonium (TMA) group of choline can be detected with 1H-MRS at 3.20 ppm. Here, we investigated the relationship between intrahepatic choline levels and hepatic lipid content on healthy overweight/obese subjects using 1H-MRS at 3 Tesla. Our results showed that high hepatic lipid content is associated with low choline content in the liver.
Introduction:
Non-alcoholic fatty liver (NAFL) is becoming a major health problem in our westernized society and can ultimately progress into serious hepatic conditions, including non-alcoholic steatohepatitis (NASH). Animal studies have suggested that disturbances in choline metabolism may accelerate the development of NAFL. Choline deficiency has been shown to induce fatty liver in experimental animal studies,1 but to date, human data is scarce. Previous epidemiological studies showed that self-reported habitual dietary choline intake is negatively associated with risk for NAFL.2-4. Although very intriguing, the exact mechanistic link between choline and fatty liver remains elusive. The non-invasive detection of choline in human liver might help to unravel this link. The trimethylammonium (TMA) resonance which can be detected by 1H-MRS at 3.20 ppm5,6 is very interesting in that respect, as it mainly reflects choline abundance. Here, we investigated the relationship between hepatic TMA (interpreted as choline content) and lipid content using 1H-MRS.Materials and Methods:
All experiments were performed on a 3T MR system (Achieva 3T-X, Philips Healthcare, Best, Netherlands) by using a 32-channel sense cardiac/torso coil (Philips Healthcare, Best, Netherlands). A total of 15 healthy overweight/obese males (n=7) and females (n=8), age between 45-70 years and BMI between 27-35 kg/m2, were included in this study. In vivo hepatic lipid spectra were acquired using STEAM (TR/TE=4500/20 ms, NSA=128, Voxel=30x30x30 mm,) combined with VAPOR water suppression. The TR of 4500 ms was chosen to allow subjects breathing in the rhythm of the measurement (acquisition at end expiration). All obtained hepatic lipid spectra were post-processed in a home-written MATLAB script (including frequency and phase alignment, baseline correction and fitting of the target resonances). The tissue content of choline was expressed as the ratio of TMA/water resonance and hepatic lipid fraction was expressed (without T2 correction) as the ratio of CH2/(CH2+water) resonances.Results and discussion:
The signal intensity of the choline (TMA) resonance was found to be low in subjects with high hepatic lipid content (Fig 1). We found a significant negative correlation (P=0.005; R2=0.47) between choline and hepatic lipid fraction (Fig 2), over a wide range of hepatic lipid (from 0.9% to 20%). There was no significant correlation between choline and age (P=0.52; R2=0.03) and BMI (P=0.09; R2=0.20), which may also be due to the narrow range of BMI and age in the current study. Interventional studies will have to investigate whether the association found here reflects a causal relationship and whether normalization of choline is beneficial to metabolic health.Conclusion:
Our results indicate that high hepatic lipid fraction is associated with low choline content in the liver in vivo.Acknowledgements
The collaboration project is financed by the Ministry of Economic Affairs and Climate Policy by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships.References
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