Background: Heart failure (HF) is often associated with iron deficiency (ID). Skeletal muscle abnormalities are common in HF, but the potential role of ID in this phenomenon is unclear. In addition to hemopoiesis, iron is essential for muscle bioenergetics. We examined whether energetic abnormalities in skeletal muscle in HF are affected by ID and if they are responsive to intravenous iron. Methods and Results: Forty-four chronic HF subjects and 25 similar healthy volunteers underwent ³¹ P magnetic resonance spectroscopy of calf muscle at rest and during exercise (plantar flexions). Results were compared between HF subjects with or without ID. In 13 ID-HF subjects, examinations were repeated 1 month after intravenous ferric carboxymaltose administration (1000 mg). As compared with controls, HF subjects displayed lower resting high-energy phosphate content, lower exercise pH, and slower postexercise PCr recovery. Compared with non-ID HF, ID-HF subjects had lower muscle strength, larger PCr depletion, and more profound intracellular acidosis with exercise, consistent with an earlier metabolic shift to anaerobic glycolysis. The exercise-induced PCr drop strongly correlated with pH change in HF group ( r =−0.71, P <0.001) but not in controls ( r =0.13, P =0.61, interaction: P <0.0001). Short-term iron administration corrected the iron deficit but had no effect on muscle bioenergetics assessed 1 month later. Conclusions: HF patients display skeletal muscle myopathy that is more severe in those with iron deficiency. The presence of ID is associated with greater acidosis with exercise, which may explain early muscle fatigue. Further study is warranted to identify the strategy to restore iron content in skeletal muscle.

Diets rich in fat and added sugars (especially fructose) play an important role in the pathogenesis of nonalcoholic liver disease (NAFLD), but there is only limited information on the acute effects of these nutrients on hepatic fat content (HFC). We therefore explored how the administration of high-fat load, glucose, fructose, and combinations thereof affects HFC measured in vivo using proton magnetic resonance spectroscopy (1H-MRS) in healthy subjects. Ten healthy nonsteatotic male volunteers (age 38.5 ± 9.6 y, body mass index [BMI, kg/m2] 26.9 ± 2.7) underwent, in random order, 6 experiments, each lasting 8 h, that included: 1) fasting; 2) a high-fat load (150 g of fat [dairy cream] at time 0); 3) glucose (3 doses of 50 g at 0, 2, and 4 h); 4) a high-fat load with glucose; 5) fructose (3 doses of 50 g at 0, 2, and 4 h); and 6) a high-fat load with fructose. HFC was measured using 1H-MRS prior to test meal administration (before time 0) and at 3 and 6 h. Plasma concentrations of triglycerides, nonesterified fatty acids, glucose, and insulin were monitored throughout each experiment. HFC increased to 119 ± 19% (P < 0.05) and 117 ± 17% (P < 0.01) of baseline when subjects consumed a high-fat load alone or a high-fat load with fructose, respectively, but was not affected when glucose was coadministered with a high-fat load. HFC was not affected when subjects had fasted or had consumed repeated doses of fructose. When subjects were administered 3 doses of glucose, HFC dropped to 85 ± 13% (P < 0.05) of baseline. Our results demonstrate that fructose and glucose have a different immediate impact on HFC in humans in vivo. Clinical trial registry: The study was registered at clinicaltrials.gov and obtained clinicaltrials.gov identifier: NCT03680248.

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) represents a major clinical complication of obesity. Methods: In this study, we used magnetic resonance (MR) methods to determine the effect of obesity treatment with semaglutide, a GLP-1 receptor agonist, on the liver fat content and selected metabolic variables. We investigated whether treatment would affect the acute response of liver fat to glucose and fructose administration and whether it would affect the fatty acid profile of VLDL-triglycerides. Sixteen obese non-diabetic men underwent a 16-week dietary intervention and 16-week treatment with subcutaneous semaglutide in a crossover design without a washout period. The order of the interventions was randomized. Results: After treatment, body weight of the subjects decreased by 5% and liver fat by a third, whereas dietary intervention had no impact on these parameters. The decrease in liver fat with semaglutide did not correlate with changes in body weight and other measures of adiposity and was unrelated to improved insulin sensitivity. Conclusions: The proportion of palmitic and palmitoleic acids in VLDL-triglycerides decreased after treatment, suggesting that the beneficial effects of semaglutide on liver fat are mediated by the suppression of de novo lipogenesis.

Most in vivo ³¹P MR studies are realized on 3T MR systems that provide sufficient signal intensity for prominent phosphorus metabolites. The identification of these metabolites in the in vivo spectra is performed by comparing their chemical shifts with the chemical shifts measured in vitro on high-field NMR spectrometers. To approach in vivo conditions at 3T, a set of phantoms with defined metabolite solutions were measured in a 3T whole-body MR system at 7.0 and 7.5 pH, at 37 °C. A free induction decay (FID) sequence with and without ¹H decoupling was used. Chemical shifts were obtained of phosphoenolpyruvate (PEP), phosphatidylcholine (PtdC), phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), glycerophosphoetanolamine (GPE), uridine diphosphoglucose (UDPG), glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), 2,3-diphosphoglycerate (2,3-DPG), nicotinamide adenine dinucleotide (NADH and NAD⁺), phosphocreatine (PCr), adenosine triphosphate (ATP), adenosine diphosphate (ADP), and inorganic phosphate (Pi). The measured chemical shifts were used to construct a basis set of ³¹P MR spectra for the evaluation of ³¹P in vivo spectra of muscle and the liver using LCModel software (linear combination model). Prior knowledge was successfully employed in the analysis of previously acquired in vivo data.

Magnetic Resonance (MR) compatible ergometers are specialized ergometers used inside the MR scanners for the characterization of tissue metabolism changes during physical stress. They are most commonly used for dynamic phosphorous magnetic resonance spectroscopy (31P MRS), but can also be used for lactate production measurements, perfusion studies using arterial spin labelling or muscle oxygenation measurements by blood oxygen dependent contrast sequences. We will primarily discuss the importance of ergometers in the context of dynamic 31P MRS. Dynamic 31P MRS can monitor muscle fatigue and energy reserve during muscle contractions as well as the dynamics of recuperation of skeletal muscle tissue during the following recovery through signal changes of phosphocreatine (PCr), inorganic phosphate and adenosine triphosphate (ATP). Based on the measured data it is possible to calculate intracellular pH, metabolic flux of ATP through creatine-kinase reaction, anaerobic glycolysis and oxidative phosphorylation and other metabolic parameters as mitochondrial capacity. This review primarily focuses on describing various technical designs of MR compatible ergometers for dynamic 31P MRS that must be constructed with respect to the presence of magnetic field. It is also expected that the construction of ergometers will be easy for the handling and well accepted by examined subjects.