Andrea Egger

The Effect of Aerobic Exercise on Intrahepatocellular and Intramyocellular Lipids in Healthy Subjects

Background Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass). Aim To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy. Methods Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO2max) using 1H-MR-spectroscopy. Results Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO2max, 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (−22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity. Conclusions IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions. Trial Registration ClinicalTrial.gov NCT00491582

Standardized protocol for a depletion of intramyocellular lipids (IMCL).

Intramyocellular lipids (IMCL) are flexible fuel stores that are depleted by physical exercise and replenished by fat intake. IMCL or their degradation products are thought to interfere with insulin signaling thereby contributing to insulin resistance. From a practical point of view it is desirable to deplete IMCL prior to replenishing them. So far, it is not clear for how long and at which intensity subjects have to exercise in order to deplete IMCL. We therefore aimed at developing a standardized exercise protocol that is applicable to subjects over a broad range of exercise capacity and insulin sensitivity and allows measuring reliably reduced IMCL levels.

The effect of GH replacement therapy on different fat compartments: a whole-body magnetic resonance imaging study

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.

Effect of Growth hormone replacement therapy on soluble Klotho in patients with Growth hormone deficiency

and further reinforced it using two independent experienced physicians who verified that all PET/CT results did not include cancerous tumours. Finally, the Discussion section of our original paper provides extensive information on the potential physiological differences between patients with cancer and healthy subjects with respect to the study findings. All the above demonstrate a well-designed and thorough process as well as that the reader of our original paper is able to recognize the potential limits of performing our study in a group of individuals undergoing F-FDG PET/CT scanning, the majority of which pertained to cancer detection. In this light, it becomes clear that the concerns of Ruiz et al. have been already addressed in our original paper. We view differences in opinion as a reason for discussion, not a reason for rejection. In this light, the letter of Ruiz et al. is most welcome and exemplifies the need for further research, reflection and debate required to elucidate the physiological and molecular pathways related to the function of BAT. Having written that, however, we are compelled to note that – as shown in the previous paragraphs – three of the four issues raised by Ruiz et al. have been effectively addressed in our original paper.

Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy.

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 GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn’t significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.

Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD).

OBJECTIVE Growth hormone (GH) has a strong lipolytic action and its secretion is increased during exercise. Data on fuel metabolism and its hormonal regulation during prolonged exercise in patients with growth hormone deficiency (GHD) is scarce. This study aimed at evaluating the hormonal and metabolic response during aerobic exercise in GHD patients. DESIGN Ten patients with confirmed GHD and 10 healthy control individuals (CI) matched for age, sex, BMI, and waist performed a spiroergometric test to determine exercise capacity (VO2max). Throughout a subsequent 120-minute exercise on an ergometer at 50% of individual VO2max free fatty acids (FFA), glucose, GH, cortisol, catecholamines and insulin were measured. Additionally substrate oxidation assessed by indirect calorimetry was determined at begin and end of exercise. RESULTS Exercise capacity was lower in GHD compared to CI (VO2max 35.5±7.4 vs 41.5±5.5ml/min∗kg, p=0.05). GH area under the curve (AUC-GH), peak-GH and peak-FFA were lower in GHD patients during exercise compared to CI (AUC-GH 100±93.2 vs 908.6±623.7ng∗min/ml, p<0.001; peak-GH 1.5±1.53 vs 12.57±9.36ng/ml, p<0.001, peak-FFA 1.01±0.43 vs 1.51±0.56mmol/l, p=0.036, respectively). There were no significant differences for insulin, cortisol, catecholamines and glucose. Fat oxidation at the end of exercise was higher in CI compared to GHD patients (295.7±73.9 vs 187.82±103.8kcal/h, p=0.025). CONCLUSION A reduced availability of FFA during a 2-hour aerobic exercise and a reduced fat oxidation at the end of exercise may contribute to the decreased exercise capacity in GHD patients. Catecholamines and cortisol do not compensate for the lack of the lipolytic action of GH in patients with GHD.