Johan Berglund

Effects of n−6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial

BACKGROUND Replacing SFAs with vegetable PUFAs has cardiometabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs have, however, also been proposed to promote inflammation-a yet unproven theory. OBJECTIVE We investigated the effects of PUFAs on liver fat, systemic inflammation, and metabolic disorders. DESIGN We randomly assigned 67 abdominally obese subjects (15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet), without altering the macronutrient intake. Liver fat was assessed by MRI and magnetic resonance proton (1H) spectroscopy (MRS). Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic LDL-receptor regulator), inflammation, and adipose tissue expression of inflammatory and lipogenic genes were determined. RESULTS A total of 61 subjects completed the study. Body weight modestly increased but was not different between groups. Liver fat was lower during the PUFA diet than during the SFA diet [between-group difference in relative change from baseline; 16% (MRI; P < 0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2 (P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were lower during the PUFA diet, whereas insulin (P = 0.06) tended to be higher during the SFA diet. In compliant subjects (defined as change in serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides were lower during the PUFA diet than during the SFA diet (P < 0.05). Adipose tissue gene expression was unchanged. CONCLUSIONS Compared with SFA intake, n-6 PUFAs reduce liver fat and modestly improve metabolic status, without weight loss. A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress. Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs. This trial was registered at clinicaltrials.gov as NCT01038102.

Two‐point dixon method with flexible echo times

The two‐point Dixon method is a proton chemical shift imaging technique that produces separated water‐only and fat‐only images from a dual‐echo acquisition. It is shown how this can be achieved without the usual constraints on the echo times. A signal model considering spectral broadening of the fat peak is proposed for improved water/fat separation. Phase errors, mostly due to static field inhomogeneity, must be removed prior to least‐squares estimation of water and fat. To resolve ambiguity of the phase errors, a corresponding global optimization problem is formulated and solved using a message‐passing algorithm. It is shown that the noise in the water and fat estimates matches the Cramér‐Rao bounds, and feasibility is demonstrated for in vivo abdominal breath‐hold imaging. The water‐only images were found to offer superior fat suppression compared with conventional spectrally fat suppressed images. Magn Reson Med, 2010.

Three‐dimensional water/fat separation and T 2* estimation based on whole‐image optimization—Application in breathhold liver imaging at 1.5 T

The chemical shift of water and fat resonances in proton MRI allows separation of water and fat signal from chemical shift encoded data. This work describes an automatic method that produces separate water and fat images as well as quantitative maps of fat signal fraction and T  2* from complex multiecho gradient‐recalled datasets. Accurate water and fat separation is challenging due to signal ambiguity at the voxel level. Whole‐image optimization can resolve this ambiguity, but might be computationally demanding, especially for three‐dimensional data. In this work, periodicity of the model fit residual as a function of the off‐resonance was used to modify a previously proposed formulation of the problem. This gives a smaller solution space and allows rapid optimization. Feasibility and accurate separation of water and fat signal were demonstrated in breathhold three‐dimensional liver imaging of 10 volunteer subjects, with both acquisition and reconstruction times below 20 s. Magn Reson Med, 2011.

Bisphenol A exposure increases liver fat in juvenile fructose-fed Fischer 344 rats

BACKGROUND Prenatal exposure to bisphenol A (BPA) has been shown to induce obesity in rodents. To evaluate if exposure also later in life could induce obesity or liver damage we investigated these hypothesises in an experimental rat model. METHODS From five to fifteen weeks of age, female Fischer 344 rats were exposed to BPA via drinking water (0.025, 0.25 or 2.5 mg BPA/L) containing 5% fructose. Two control groups were given either water or 5% fructose solution. Individual weight of the rats was determined once a week. At termination magnetic resonance imaging was used to assess adipose tissue amount and distribution, and liver fat content. After sacrifice the left perirenal fat pad and the liver were dissected and weighed. Apolipoprotein A-I in plasma was analyzed by western blot. RESULTS No significant effects on body weight or the weight of the dissected fad pad were seen in rats exposed to BPA, and MRI showed no differences in total or visceral adipose tissue volumes between the groups. However, MRI showed that liver fat content was significantly higher in BPA-exposed rats than in fructose controls (p=0.04). BPA exposure also increased the apolipoprotein A-I levels in plasma (p<0.0001). CONCLUSION We found no evidence that BPA exposure affects fat mass in juvenile fructose-fed rats. However, the finding that BPA in combination with fructose induced fat infiltration in the liver at dosages close to the current tolerable daily intake (TDI) might be of concern given the widespread use of this compound in our environment.

Model‐based mapping of fat unsaturation and chain length by chemical shift imaging—phantom validation and in vivo feasibility

Knowledge about the triglyceride (fat) 1H spectrum enables quantitative determination of several triglyceride characteristics. This work describes a model‐based chemical shift imaging method that separates water and fat signal and provides maps of three triglyceride quantities: fatty acid carbon chain length, unsaturation degree, and polyunsaturation degree. The method was validated by imaging a phantom containing 10 different oils using 1.5 and 3.0 T clinical scanners, with gas–liquid chromatography as reference. Repeated acquisitions demonstrated high reproducibility of the method. Statistical tests of correlation and linear regression were performed to examine the accuracy of the method. Significant correlation was found at both field strengths for all three quantities, and high correlation (r2 > 0.95) was found for measuring unsaturation degree and polyunsaturation degree. Feasibility of the method for in vivo imaging of the thigh was demonstrated at both field strengths. The estimates of unsaturation degree and polyunsaturation degree in subcutaneous adipose tissue were in agreement with literature values, while chain length appeared over estimated. The method has potential use in large‐scale cross‐sectional and longitudinal studies of triglyceride composition, and its relation to diet and various diseases. Magn Reson Med, 2012.

Comparison of Gross Body Fat-Water Magnetic Resonance Imaging at 3 Tesla to Dual Energy X-Ray Absorptiometry in Obese Women

Improved understanding of how depot‐specific adipose tissue mass predisposes to obesity‐related comorbidities could yield new insights into the pathogenesis and treatment of obesity as well as metabolic benefits of weight loss. We hypothesized that three‐dimensional (3D) contiguous “fat‐water” MR imaging (FWMRI) covering the majority of a whole‐body field of view (FOV) acquired at 3 Tesla (3T) and coupled with automated segmentation and quantification of amount, type, and distribution of adipose and lean soft tissue would show great promise in body composition methodology.

Quantification of total and visceral adipose tissue in fructose-fed rats using water-fat separated single echo MRI

The aim of this study was to setup a rodent model for modest weight gain and an MRI‐based quantification of body composition on a clinical 1.5 T MRI system for studies of obesity and environmental factors and their possible association.

Canine body composition quantification using 3 tesla fat–water MRI

To test the hypothesis that a whole‐body fat–water MRI (FWMRI) protocol acquired at 3 Tesla combined with semi‐automated image analysis techniques enables precise volume and mass quantification of adipose, lean, and bone tissue depots that agree with static scale mass and scale mass changes in the context of a longitudinal study of large‐breed dogs placed on an obesogenic high‐fat, high‐fructose diet.

T1 weighted fat/water separated PROPELLER acquired with dual bandwidths

To describe a fat/water separated dual receiver bandwidth (rBW) spin echo PROPELLER sequence that eliminates the dead time associated with single rBW sequences. A nonuniform noise whitening by regularization of the fat/water inverse problem is proposed, to enable dual rBW reconstructions.

Signal modeling and the Cramér-Rao Bound for absolute Magnetic Resonance thermometry in fat tissue

Magnetic Resonance Imaging of tissues with both fat and water resonances allows for absolute temperature mapping through parametric modeling. The fat resonance is used as a reference to determine the absolute water resonance frequency which is linearly related to the temperature. The goal of this paper is to assess whether or not resonance frequency based absolute temperature mapping is feasible in fat tissue. This is done by examining identifiability conditions and analyzing the obtainable performance in terms of the Cramér-Rao Bound of the temperature estimates. We develop the model by including multiple fat peaks, since even small fat resonances can be significant compared to the small water component in fat tissue. It is showed that a high signal to noise ratio is needed for practical use on a 1.5 T scanner, and that higher field strengths can improve the bound significantly. It is also shown that the choice of sampling interval is important to avoid aliasing. In sum, this type of magnetic resonance thermometry is feasible for fat tissue in applications where high field strength is used or when high signal to noise ratio can be obtained.