s u m m a r y Background & aims: High protein diets have been shown to improve hepatic steatosis in rodent models and in high-fat fed humans. We therefore evaluated the effects of a protein supplementation on intra-hepatocellular lipids... more
s u m m a r y Background & aims: High protein diets have been shown to improve hepatic steatosis in rodent models and in high-fat fed humans. We therefore evaluated the effects of a protein supplementation on intra-hepatocellular lipids (IHCL), and fasting plasma triglycerides in obese non diabetic women. Methods: Eleven obese women received a 60 g/day whey protein supplement (WPS) for 4-weeks, while otherwise nourished on a spontaneous diet, IHCL concentrations, visceral body fat, total liver volume (MR), fasting total-triglyceride and cholesterol concentrations, glucose tolerance (standard 75 g OGTT), insulin sensitivity (HOMA IS index), creatinine clearance, blood pressure and body composition (bio-impedance analysis) were assessed before and after 4-week WPS. Results: IHCL were positively correlated with visceral fat and total liver volume at inclusion. WPS decreased significantly IHCL by 20.8 AE 7.7%, fasting total TG by 15 AE 6.9%, and total cholesterol by 7.3 AE 2.7%. WPS slightly increased fat free mass from 54.8 AE 2.2 kg to 56.7 AE 2.5 kg, p ¼ 0.005). Visceral fat, total liver volume, glucose tolerance, creatinine clearance and insulin sensitivity were not changed. Conclusions: WPS improves hepatic steatosis and plasma lipid profiles in obese non diabetic patients, without adverse effects on glucose tolerance or creatinine clearance. Trial Number: NCT00870077, ClinicalTrials.gov
Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids... more
Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after...
(31) P MRS magnetization transfer ((31) P-MT) experiments allow the estimation of exchange rates of biochemical reactions, such as the creatine kinase equilibrium and adenosine triphosphate (ATP) synthesis. Although various (31) P-MT... more
(31) P MRS magnetization transfer ((31) P-MT) experiments allow the estimation of exchange rates of biochemical reactions, such as the creatine kinase equilibrium and adenosine triphosphate (ATP) synthesis. Although various (31) P-MT methods have been successfully used on isolated organs or animals, their application on humans in clinical scanners poses specific challenges. This study compared two major (31) P-MT methods on a clinical MR system using heteronuclear surface coils. Although saturation transfer (ST) is the most commonly used (31) P-MT method, sequences such as inversion transfer (IT) with short pulses might be better suited for the specific hardware and software limitations of a clinical scanner. In addition, small NMR-undetectable metabolite pools can transfer MT to NMR-visible pools during long saturation pulses, which is prevented with short pulses. (31) P-MT sequences were adapted for limited pulse length, for heteronuclear transmit-receive surface coils with inhomogeneous B1 , for the need for volume selection and for the inherently low signal-to-noise ratio (SNR) on a clinical 3-T MR system. The ST and IT sequences were applied to skeletal muscle and liver in 10 healthy volunteers. Monte-Carlo simulations were used to evaluate the behavior of the IT measurements with increasing imperfections. In skeletal muscle of the thigh, ATP synthesis resulted in forward reaction constants (k) of 0.074 ±0.022 s(-1) (ST) and 0.137 ±0.042 s(-1) (IT), whereas the creatine kinase reaction yielded 0.459 ±0.089 s(-1) (IT). In the liver, ATP synthesis resulted in k = 0.267 ±0.106 s(-1) (ST), whereas the IT experiment yielded no consistent results. ST results were close to literature values; however, the IT results were either much larger than the corresponding ST values and/or were widely scattered. To summarize, ST and IT experiments can both be implemented on a clinical body scanner with heteronuclear transmit-receive surface coils; however, ST results are much more robust against experimental imperfections than the current implementation of IT. Copyright © 2014 John Wiley & Sons, Ltd.
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To investigate the inhomogeneity of radiofrequency fields at higher field strengths that can interfere with established volumetric methods, in particular for the determination of visceral (VAT) and subcutaneous adipose tissue (SCAT). A... more
To investigate the inhomogeneity of radiofrequency fields at higher field strengths that can interfere with established volumetric methods, in particular for the determination of visceral (VAT) and subcutaneous adipose tissue (SCAT). A versatile, interactive sparse sampling (VISS) method is proposed to determine VAT, SCAT, and also total body volume (TBV). VISS is based on a separation of major components by contour lines, followed by a sparse sampling algorithm, and eventually a quick manual correction. T1-weighted whole body scans of 24 subjects were evaluated (12 at 1.5T, 12 at 3.0T). (a) Coefficients of variance (CV) and intra class correlation coefficients (ICC) determined within 3 raters (24 subjects) showed high consistency for SCAT (CV 2.2%, ICC 0.993) and VAT (CV 4.9%, ICC 0.987), (b) comparison with an established volumetric method revealed good agreement (Bland-Altman, VAT -0.68L to 1.07L, SCAT -2.18L to 8.39L), and (c) comparison of weights calculated from TBV with values measured on a scale resulted in an even better accuracy for VISS (Bland-Altman -1.98 kg to 4.09 kg) than for the reference method (-5.60 kg to 1.60 kg). VISS is reproducible in particular within the same rater, accurate as compared with established methods, and robust against low contrast and inhomogeneity artifacts.
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Patients with GH deficiency (GHD) are insulin resistant with an increase in visceral fat mass (FM). Whether this holds true when sedentary control subjects (CS) are matched for waist has not been documented. GH replacement therapy (GHRT)... more
Patients with GH deficiency (GHD) are insulin resistant with an increase in visceral fat mass (FM). Whether this holds true when sedentary control subjects (CS) are matched for waist has not been documented. GH replacement therapy (GHRT) results in a decrease in FM. Whether the decrease in FM is mainly related to a reduction in visceral FM remains to be proven. The aim was to separately assess visceral and subcutaneous FM in relation to insulin resistance (IR) in GHD patients before and after GHRT and in sedentary CS. Ten patients with GHD were investigated before and 6 months after GHRT. Sedentary CS matched for age, gender, body mass index, and waist were assessed. Exercise capacity was measured as VO(2max) using an incremental work load on a treadmill. Visceral and subcutaneous FM were measured using whole-body magnetic resonance imaging and IR by the homeostasis model assessment of IR (HOMA-IR) index. GHD patients had a non-significantly lower VO(2max) but did not have increased subcutaneous and visceral FM compared with CS. GHRT resulted in a similar relative decrease in subcutaneous and visceral FM. Compared with CS, GHD patients showed a lower HOMA-IR. GHRT tended to increase HOMA-IR. Matching for waist and separate assessment of visceral and subcutaneous FM may be critical in the evaluation of body composition and IR in GHD patients before and after GHRT.