Background Increased fructose intake has been associated with metabolic consequences such as impaired hepatic lipid metabolism and development of nonalcoholic fatty liver disease (NAFLD). Objectives The aim of this study was to investigate the role of fructose in glucose and lipid metabolism in the liver, heart, skeletal muscle, and adipose tissue. Methods Ten healthy subjects (age: 28 ± 19 y; BMI: 22.2 ± 0.7 kg/m2) underwent comprehensive metabolic phenotyping prior to and 8 wk following a high-fructose diet (150 g daily). Eleven patients with NAFLD (age: 39.4 ± 3.95 y; BMI: 28.4 ± 1.25) were characterized as “positive controls.” Insulin sensitivity was analyzed by a 2-step hyperinsulinemic euglycemic clamp, and postprandial interorgan crosstalk of lipid and glucose metabolism was evaluated, by determining postprandial hepatic and intra-myocellular lipid and glycogen accumulation, employing magnetic resonance spectroscopy (MRS) at 7 T. Myocardial lipid content and myocardial function were assessed by 1H MRS imaging and MRI at 3 T. Results High fructose intake resulted in lower intake of other dietary sugars and did not increase total daily energy intake. Ectopic lipid deposition and postprandial glycogen storage in the liver and skeletal muscle were not altered. Postprandial changes in hepatic lipids were measured [Δhepatocellular lipid (HCL)_healthy_baseline: −15.9 ± 10.7 compared with ± ΔHCL_healthy_follow-up: −6.9 ± 4.6; P = 0.17] and hepatic glycogen (Δglycogen_baseline: 64.4 ± 14.1 compared with Δglycogen_follow-up: 51.1 ± 9.8; P = 0.42). Myocardial function and myocardial mass remained stable. As expected, impaired hepatic glycogen storage and increased ectopic lipid storage in the liver and skeletal muscle were observed in insulin-resistant patients with NAFLD. Conclusions Ingestion of a high dose of fructose for 8 wk was not associated with relevant metabolic consequences in the presence of a stable energy intake, slightly lower body weight, and potentially incomplete absorption of the orally administered fructose load. This indicated that young, metabolically healthy subjects can at least temporarily compensate for increased fructose intake. This trial was registered at www.clinicaltrials.gov as NCT02075164.

Background Hepatic disorders are often associated with changes in the concentration of phosphorus‐31 ( 31 P) metabolites. Absolute quantification offers a way to assess those metabolites directly but introduces obstacles, especially at higher field strengths (B 0 ≥ 7T). Purpose To introduce a feasible method for in vivo absolute quantification of hepatic 31 P metabolites and assess its clinical value by probing differences related to volunteers' age and body mass index (BMI). Study Type Prospective cohort. Subjects/Phantoms Four healthy volunteers included in the reproducibility study and 19 healthy subjects arranged into three subgroups according to BMI and age. Phantoms containing 31 P solution for correction and validation. Field Strength/Sequence Phase‐encoded 3D pulse‐acquire chemical shift imaging for 31 P and single‐volume 1 H spectroscopy to assess the hepatocellular lipid content at 7T. Assessment A phantom replacement method was used. Spectra located in the liver with sufficient signal‐to‐noise ratio and no contamination from muscle tissue, were used to calculate following metabolite concentrations: adenosine triphosphates (γ‐ and α‐ATP); glycerophosphocholine (GPC); glycerophosphoethanolamine (GPE); inorganic phosphate (P i ); phosphocholine (PC); phosphoethanolamine (PE); uridine diphosphate‐glucose (UDPG); nicotinamide adenine dinucleotide‐phosphate (NADH); and phosphatidylcholine (PtdC). Correction for hepatic lipid volume fraction (HLVF) was performed. Statistical Tests Differences assessed by analysis of variance with Bonferroni correction for multiple comparison and with a Student's t ‐test when appropriate. Results The concentrations for the young lean group corrected for HLVF were 2.56 ± 0.10 mM for γ‐ATP (mean ± standard deviation), α‐ATP: 2.42 ± 0.15 mM, GPC: 3.31 ± 0.27 mM, GPE: 3.38 ± 0.87 mM, P i : 1.42 ± 0.20 mM, PC: 1.47 ± 0.24 mM, PE: 1.61 ± 0.20 mM, UDPG: 0.74 ± 0.17 mM, NADH: 1.21 ± 0.38 mM, and PtdC: 0.43 ± 0.10 mM. Differences found in ATP levels between lean and overweight volunteers vanished after HLVF correction. Data Conclusion Exploiting the excellent spectral resolution at 7T and using the phantom replacement method, we were able to quantify up to 10 31 P‐containing hepatic metabolites. The combination of 31 P magnetic resonance spectroscopy imaging data acquisition and HLVF correction was not able to show a possible dependence of 31 P metabolite concentrations on BMI or age, in the small hea...

BackgroundObesity is a major risk factor to develop heart failure, in part due to possible lipotoxic effects of increased intramyocardial (MYCL) and/or local or paracrine effects of pericardial (PERI) lipid accumulation. Recent evidence suggests that MYCL is highly dynamic and might rather be a surrogate marker for disturbed energy metabolism than the underlying cause of cardiac dysfunction. On the other hand, PERI might contribute directly by mechanic and paracrine effects. Therefore, we hypothesized that PERI rather than MYCL is associated with myocardial function.MethodsTo avoid potential confounding of metabolic disease 31 metabolically healthy subjects (age: 29±10yrs; BMI: 23±3kg/m2) were investigated using 1H-magnetic resonance spectroscopy and imaging. MYCL and PERI, as well as systolic and diastolic left ventricular heart function were assessed. Additionally, anthropometric data and parameters of glucose and lipid metabolism were analyzed. Correlation analysis was performed using Pearson’s correlation coefficient. Linear regression model was used to show individual effects of PERI and MYCL on myocardial functional parameters.ResultsCorrelation analysis with parameters of systolic heart function revealed significant associations for PERI (Stroke Volume (SV): R = -0.513 p = 0.001; CardiacIndex (CI): R = -0.442 p = 0.014), but not for MYCL (SV: R = -0.233; p = 0.207; CI: R = -0.130; p = 0.484). No significant correlations were found for E/A ratio as a parameter of diastolic heart function. In multiple regression analysis CI was negatively predicted by PERI, whereas no impact of MYCL was observed in direct comparison.ConclusionsCardiac fat depots impact left ventricular heart function in a metabolically healthy population. Direct comparison of different lipid stores revealed that PERI is a more important predictor than MYCL for altered myocardial function.

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Context: Nonalcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown.Objective: Here we assessed if intranasal insulin, a method to preferentially deliver insulin to the central nervous system, is able to modulate hepatic lipid content and plasma BCAAs in humans.Design/Setting: We conducted a randomized, double-blind, placebo-controlled trial at the Medical University of Vienna. Participants/Intervention:We assessed if a chronic 4-week intranasal insulin treatment (40 IU, 4 times daily) reduces hepatic triglyceride content and circulating BCAAs in 20 healthy male volunteers.Main Outcome Measures: Hepatic lipid content was assessed noninvasively by 1 H-magnetic resonance spectroscopy, and BCAAs were measured by gas chromatography mass spectrometry at defined time points during the study.Results: Chronic intranasal insulin treatment did not alter body weight, body mass index, and hepatic lipid content but reduced circulating BCAA levels.Conclusions: These findings support the notion that brain insulin controls BCAA metabolism in humans. Thus, brain insulin resistance could account at least in part for the elevated BCAA levels observed in the insulin-resistant state. (J Clin Endocrinol Metab 102: 1325-1332, 2017 L iver steatosis is closely associated with obesity and type 2 diabetes and represents the hepatic manifestation of the metabolic syndrome. Hepatic steatosis results from a net retention of lipids in the liver; thus, a key mechanism for the liver to fend off steatosis is to increase hepatic triglyceride (TG) export. The enhancement of brain insulin signaling in rodents through a chronic insulin infusion into the third ventricle increases hepatic