Andreas Boss

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans

To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short‐term overfeeding in healthy subjects.

Skeletal Muscle Mitochondria in the Elderly: Effects of Physical Fitness and Exercise Training

CONTEXTnSarcopenia is thought to be associated with mitochondrial (Mito) loss. It is unclear whether the decrease in Mito content is consequent to aging per se or to decreased physical activity.nnnOBJECTIVESnThe objective of the study was to examine the influence of fitness on Mito content and function and to assess whether exercise could improve Mito function in older adults.nnnDESIGN AND SUBJECTSnThree distinct studies were conducted: 1) a cross-sectional observation comparing Mito content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adults and sedentary (S) subjects matched for age and gender; and 3) a 4-month exercise intervention in S.nnnSETTINGnThe study was conducted at a university-based clinical research center.nnnOUTCOMESnMito volume density (MitoVd) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins by Western blotting, mRNAs for transcription factors involved in M biogenesis by quantitative RT-PCR, and in vivo oxidative capacity (ATPmax) by (31)P-magnetice resonance spectroscopy. Peak oxygen uptake was measured by graded exercise test.nnnRESULTSnPeak oxygen uptake was strongly correlated with MitoVd in 80 60- to 80-year-old adults. Comparison of chronically endurance-trained older adults vs S revealed differences in MitoVd, ATPmax, and some electron transport chain protein complexes. Finally, exercise intervention confirmed that S subjects are able to recover MitoVd, ATPmax, and specific transcription factors.nnnCONCLUSIONSnThese data suggest the following: 1) aging per se is not the primary culprit leading to Mito dysfunction; 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle Mito content and may prevent aging muscle comorbidities; and 3) the improvement of Mito function is all about content.

Effects of a whey protein supplementation on intrahepatocellular lipids in obese female patients

BACKGROUND & AIMSnHigh 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 intrahepatocellular lipids (IHCL), and fasting plasma triglycerides in obese non diabetic women.nnnMETHODSnEleven obese women received a 60xa0g/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 75xa0g OGTT), insulin sensitivity (HOMA IS index), creatinine clearance, blood pressure and body composition (bio-impedance analysis) were assessed before and after 4-week WPS.nnnRESULTSnIHCL were positively correlated with visceral fat and total liver volume at inclusion. WPS decreased significantly IHCL by 20.8xa0±xa07.7%, fasting total TG by 15xa0±xa06.9%, and total cholesterol by 7.3xa0±xa02.7%. WPS slightly increased fat free mass from 54.8xa0±xa02.2xa0kg to 56.7xa0±xa02.5xa0kg, pxa0=xa00.005). Visceral fat, total liver volume, glucose tolerance, creatinine clearance and insulin sensitivity were not changed.nnnCONCLUSIONSnWPS improves hepatic steatosis and plasma lipid profiles in obese non diabetic patients, without adverse effects on glucose tolerance or creatinine clearance.nnnTRIAL NUMBERnNCT00870077, ClinicalTrials.gov.

Coffee consumption attenuates short-term fructose-induced liver insulin resistance in healthy men

BACKGROUNDnEpidemiologic and experimental data have suggested that chlorogenic acid, which is a polyphenol contained in green coffee beans, prevents diet-induced hepatic steatosis and insulin resistance.nnnOBJECTIVEnWe assessed whether the consumption of chlorogenic acid-rich coffee attenuates the effects of short-term fructose overfeeding, dietary conditions known to increase intrahepatocellular lipids (IHCLs), and blood triglyceride concentrations and to decrease hepatic insulin sensitivity in healthy humans.nnnDESIGNnEffects of 3 different coffees were assessed in 10 healthy volunteers in a randomized, controlled, crossover trial. IHCLs, hepatic glucose production (HGP) (by 6,6-d2 glucose dilution), and fasting lipid oxidation were measured after 14 d of consumption of caffeinated coffee high in chlorogenic acid (C-HCA), decaffeinated coffee high in chlorogenic acid, or decaffeinated coffee with regular amounts of chlorogenic acid (D-RCA); during the last 6 d of the study, the weight-maintenance diet of subjects was supplemented with 4 g fructose · kg(-1) · d(-1) (total energy intake ± SD: 143 ± 1% of weight-maintenance requirements). All participants were also studied without coffee supplementation, either with 4 g fructose · kg(-1) · d(-1) (high fructose only) or without high fructose (control).nnnRESULTSnCompared with the control diet, the high-fructose diet significantly increased IHCLs by 102 ± 36% and HGP by 16 ± 3% and decreased fasting lipid oxidation by 100 ± 29% (all P < 0.05). All 3 coffees significantly decreased HGP. Fasting lipid oxidation increased with C-HCA and D-RCA (P < 0.05). None of the 3 coffees significantly altered IHCLs.nnnCONCLUSIONSnCoffee consumption attenuates hepatic insulin resistance but not the increase of IHCLs induced by fructose overfeeding. This effect does not appear to be mediated by differences in the caffeine or chlorogenic acid content. This trial was registered at clinicaltrials.gov as NCT00827450.

Training in hypoxia fails to further enhance endurance performance and lactate clearance in well‐trained men and impairs glucose metabolism during prolonged exercise

The aim of this study was to investigate the synergistic effects of endurance training and hypoxia on endurance performance in normoxic and hypoxic conditions (∼3000 m above sea level) as well as on lactate and glucose metabolism during prolonged exercise. For this purpose, 14 well‐trained cyclists performed 12 training sessions in conditions of normobaric hypoxia (HYP group, n= 7) or normoxia (NOR group, n= 7) over 4 weeks. Before and after training, lactate and glucose turnover rates were measured by infusion of exogenous lactate and stable isotope tracers. Endurance performance was assessed during incremental tests performed in normoxia and hypoxia and a 40 km time trial performed in normoxia. After training, performance was similarly and significantly improved in the NOR and HYP groups (training, P < 0.001) in normoxic conditions. No further effect of hypoxic training was found on markers of endurance performance in hypoxia (training × hypoxia interaction, n.s.). In addition, training and hypoxia had no significant effect on lactate turnover rate. In contrast, there was a significant interaction of training and hypoxia (P < 0.05) on glucose metabolism, as follows: plasma insulin and glucose concentrations were significantly increased; glucose metabolic clearance rate was decreased; and the insulin to glucagon ratio was increased after training in the HYP group. In conclusion, our results show that, compared with training in normoxia, training in hypoxia has no further effect on endurance performance in both normoxic and hypoxic conditions or on lactate metabolic clearance rate. Additionally, these findings suggest that training in hypoxia impairs blood glucose regulation in endurance‐trained subjects during exercise.

Skeletal muscle 1H MRSI before and after prolonged exercise. I. muscle specific depletion of intramyocellular lipids

Aim of the study was to determine distribution and depletion patterns of intramyocellular lipids (IMCL) in leg muscles before and after two types of standardized endurance exercise. 1H‐magnetic resonance spectroscopic imaging was performed ( 1 ) in the thigh of eight‐trained cyclists after exercising on an ergometer for 3 h at 52 ± 8% of maximal speed and ( 2 ) in the lower leg of eight‐trained runners after exercising on a treadmill for 3 h at 49 ± 3% of maximal workload. Pre‐exercise IMCL contents were reduced postexercise in 11 out of 13 investigated upper and lower leg muscles (P < 0.015 for all). A strong linear correlation with a slope of ∼0.5 between pre‐exercise IMCL content and IMCL depletion was found. IMCL depletion differed strongly between muscles. Absolute and also relative IMCL reduction was significantly higher in muscles with predominantly slow fibers compared to those with fast fibers. Creatine levels and fiber orientation were stable and unchanged after exercise, while trimethyl‐ammonium groups increased. This is presented in the accompanying paper. In conclusion, a systematic comparison of metabolic changes in cross sections of the upper and lower leg was performed. The results imply that pre‐exercise IMCL levels determine the degree of IMCL depletion after exercise. Magn Reson Med, 2012.

Exercise efficiency relates with mitochondrial content and function in older adults

Chronic aerobic exercise has been shown to increase exercise efficiency, thus allowing less energy expenditure for a similar amount of work. The extent to which skeletal muscle mitochondria play a role in this is not fully understood, particularly in an elderly population. The purpose of this study was to determine the relationship of exercise efficiency with mitochondrial content and function. We hypothesized that the greater the mitochondrial content and/or function, the greater would be the efficiencies. Thirty‐eight sedentary (S, n = 23, 10F/13M) or athletic (A, n = 15, 6F/9M) older adults (66.8 ± 0.8 years) participated in this cross sectional study. V˙ O2peak was measured with a cycle ergometer graded exercise protocol (GXT). Gross efficiency (GE, %) and net efficiency (NE, %) were estimated during a 1‐h submaximal test (55% V˙ O2peak). Delta efficiency (DE, %) was calculated from the GXT. Mitochondrial function was measured as ATPmax (mmol/L/s) during a PCr recovery protocol with 31P‐MR spectroscopy. Muscle biopsies were acquired for determination of mitochondrial volume density (MitoVd, %). Efficiencies were 17% (GE), 14% (NE), and 16% (DE) higher in A than S. MitoVD was 29% higher in A and ATPmax was 24% higher in A than in S. All efficiencies positively correlated with both ATPmax and MitoVd. Chronically trained older individuals had greater mitochondrial content and function, as well as greater exercise efficiencies. GE, NE, and DE were related to both mitochondrial content and function. This suggests a possible role of mitochondria in improving exercise efficiency in elderly athletic populations and allowing conservation of energy at moderate workloads.

Noninvasive Assessment of Exercise-Related Intramyocellular Acetylcarnitine in Euglycemia and Hyperglycemia in Patients With Type 1 Diabetes Using 1H Magnetic Resonance Spectroscopy: A randomized single-blind crossover study

OBJECTIVE Intramyocellular acetylcarnitine (IMAC) is involved in exercise-related fuel metabolism. It is not known whether levels of systemic glucose influence IMAC levels in type 1 diabetes. RESEARCH DESIGN AND METHODS Seven male individuals with type 1 diabetes performed 120 min of aerobic exercise at 55–60% of Vo2max randomly on two occasions (glucose clamped to 5 or 11 mmol/l, identical insulinemia). Before and after exercise, IMAC was detected by 1H magnetic resonance spectroscopy in musculus vastus intermedius. RESULTS Postexercise levels of IMAC were significantly higher than pre-exercise values in euglycemia (4.30 ± 0.54 arbitrary units [a.u.], P < 0.001) and in hyperglycemia (2.44 ± 0.53 a.u., P = 0.01) and differed significantly according to glycemia (P < 0.01). The increase in exercise-related levels of IMAC was significantly higher in euglycemia (3.97 ± 0.45 a.u.) than in hyperglycemia (1.71 ± 0.50 a.u.; P < 0.01). CONCLUSIONS The increase in IMAC associated with moderate aerobic exercise in individuals with type 1 diabetes was significantly higher in euglycemia than in hyperglycemia.

Combined effects of endurance training and dietary unsaturated fatty acids on physical performance, fat oxidation and insulin sensitivity

Endurance training improves exercise performance and insulin sensitivity, and these effects may be in part mediated by an enhanced fat oxidation. Since n-3 and n-9 unsaturated fatty acids may also increase fat oxidation, we hypothesised that a diet enriched in these fatty acids may enhance the effects of endurance training on exercise performance, insulin sensitivity and fat oxidation. To assess this hypothesis, sixteen normal-weight sedentary male subjects were randomly assigned to an isoenergetic diet enriched with fish and olive oils (unsaturated fatty acid group (UFA): 52 % carbohydrates, 34 % fat (12 % SFA, 12 % MUFA, 5 % PUFA), 14 % protein), or a control diet (control group (CON): 62 % carbohydrates, 24 % fat (12 % SFA, 6 % MUFA, 2 % PUFA), 14 % protein) and underwent a 10 d gradual endurance training protocol. Exercise performance was evaluated by measuring VO2max and the time to exhaustion during a cycling exercise at 80 % VO2max; glucose homeostasis was assessed after ingestion of a test meal. Fat oxidation was assessed by indirect calorimetry at rest and during an exercise at 50 % VO2max. Training significantly increased time to exhaustion, but not VO2max, and lowered incremental insulin area under the curve after the test meal, indicating improved insulin sensitivity. Those effects were, however, of similar magnitude in UFA and CON. Fat oxidation tended to increase in UFA, but not in CON. This difference was, however, not significant. It is concluded that a diet enriched with fish- and olive oil does not substantially enhance the effects of a short-term endurance training protocol in healthy young subjects.

Skeletal muscle 1H MRSI before and after prolonged exercise. II. visibility of free carnitine

Carnitine (Car) buffers excess acetyl‐CoA through the formation of acetylCar (AcCar). AcCars acetyl group (AG‐AcCar) gives rise to a peak at 2.13 ppm in 1H MR spectra of skeletal muscle, whereas the trimethylammonium (TMA) groups of both, AcCar and Car, are thought to contribute to the TMA peak at 3.23 ppm. Surprisingly, in previous studies both resonances, AG‐AcCar and TMA, increased after exercise. The aim of this study was to assess if the exercise‐related TMA increase correlated with AcCar production. Magnetic resonance spectroscopic imaging (pulse repetition time/echo time = 1200/35 ms) was performed before and after prolonged exercise in the lower leg and thigh of eight runners and eight cyclists, respectively. TMA and AG‐AcCar increased after exercise (P < 0.001). TMAs increase correlated with the AG‐AcCar increase (R2 = 0.73, P < 0.001, lower leg; R2 = 0.28, P < 0.001, thigh). The correlation of ΔTMA with ΔAG‐AcCar suggests that the TMA increase is due to AcCar formation. As total Car (Car + AcCar) remains unchanged with exercise, these findings suggest that the contribution of free Car to the TMA peak is limited and, therefore, is partly invisible in muscle 1H MR spectra. This indicates that the biochemically relevant cytosolic content of free Car is considerably lower than the overall concentration determined by radioisotopic assays, a potentially important result with respect to regulation of substrate oxidation. Magn Reson Med, 2012.