Energy expenditure, physical activity and body-weight control

Regular physical exercise and endurance training are associated with low body weight and low body fat mass. The relationship between exercise and body-weight control is complex and incompletely understood. Regular exercise may decrease energy balance through an increase in energy expenditure or an increase in fat oxidation. It may also contribute to weight loss by modulating nutrient intake. An intriguing question that remains unresolved is whether changes in nutrient intake or body composition secondarily affect spontaneous physical activity. If this were the case, physical activity would represent a major adaptative mechanism for body-weight contro

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus—a prospective single-blinded randomised crossover trial

Aims/hypothesis: We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels. Methods: This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type 1 diabetes (mean ± SEM age 33.5 ± 2.4years, diabetes duration 20.1 ± 3.6years, HbA1c 6.7 ± 0.2% and peak oxygen uptake [ $$\mathop {\text{V}}\limits^{\text{.}} {\text{O}}_{2{\text{peak}}}$$ ] 50.3 ± 4.5ml min−1 kg−1). Men were studied twice while cycling for 120min at 55 to 60% of $$\mathop {\text{V}}\limits^{\text{.}} {\text{O}}_{{\text{2peak}}}$$ , with a blood glucose level randomly set either at 5 or 11mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism. Results: The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 ± 4.8 vs 30.6 ± 4.2%; p < 0.05). Carbohydrate oxidation accounted for 48.2 ± 4.7 and 66.6 ± 4.2% of total energy expenditure in euglycaemia and hyperglycaemia, respectively (p < 0.05). The level of intramyocellular glycogen before exercise was higher in hyperglycaemia than in euglycaemia (3.4 ± 0.3 vs 2.7 ± 0.2 arbitrary units [AU]; p < 0.05). Absolute glycogen consumption tended to be higher in hyperglycaemia than in euglycaemia (1.3 ± 0.3 vs 0.9 ± 0.1 AU). Cortisol and growth hormone increased more strongly in euglycaemia than in hyperglycaemia (levels at the end of exercise 634 ± 52 vs 501 ± 32nmol/l and 15.5 ± 4.5 vs 7.4 ± 2.0ng/ml, respectively; p < 0.05). Conclusions/interpretation: Substrate oxidation in type 1 diabetic patients performing aerobic exercise in euglycaemia is similar to that in healthy individuals revealing a shift towards lipid oxidation during exercise. In hyperglycaemia fuel metabolism in these patients is dominated by carbohydrate oxidation. Intramyocellular glycogen was not spared in hyperglycaemia. Trial registration: ClinicalTrials.Gov NCT00325559 Funding: This study was supported by unrestricted grants from the Oetliker-Stiftung für Physiologie, from the Swiss Diabetes Foundation, from NovoNordisk, Switzerland, and from the Swiss National Science Foundatio

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Sphingolipid accumulation causes mitochondrial dysregulation and cell death

Sphingolipids are structural components of cell membranes that have signaling roles to regulate many activities, including mitochondrial function and cell death. Sphingolipid metabolism is integrated with numerous metabolic networks, and dysregulated sphingolipid metabolism is associated with disease. Here, we describe a monogenic yeast model for sphingolipid accumulation. A csg2Δ mutant cannot readily metabolize and accumulates the complex sphingolipid inositol phosphorylceramide (IPC). In these cells, aberrant activation of Ras GTPase is IPC-dependent, and accompanied by increased mitochondrial reactive oxygen species (ROS) and reduced mitochondrial mass. Survival or death of csg2Δ cells depends on nutritional status. Abnormal Ras activation in csg2Δ cells is associated with impaired Snf1/AMPK protein kinase, a key regulator of energy homeostasis. csg2Δ cells are rescued from ROS production and death by overexpression of mitochondrial catalase Cta1, abrogation of Ras hyperactivity or genetic activation of Snf1/AMPK. These results suggest that sphingolipid dysregulation compromises metabolic integrity via Ras and Snf1/AMPK pathways

Effects of glucagon on fructose-induced alterations of glucose metabolism in man.

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