Relationships between cardiorespiratory fitness/muscular strength and 18F-fluorodeoxyglucose uptake in brown adipose tissue after exposure to cold in young, sedentary adults

Humans have metabolically active brown adipose tissue (BAT). However, what is the relation between exercise or physical activity with this tissue remains controversial. Therefore, the main aim of the present study is to examine whether cardiorespiratory fitness and muscular strength are associated with brown adipose tissue (BAT) volume and activity after exposure to cold in young, sedentary adults. Cardiorespiratory fitness was determined in 119 young, healthy, sedentary adults (68% women, age 21.9 ± 2.1 years, body mass index 25 ± 4.8 kg/m2) via the maximum treadmill exercise test, and their muscular strength assessed by the handgrip strength test and the 1-repetition maximum bench and leg press tests. Some days later, all subjects were exposed to 2 h of personalized exposure to cold and their cold-induced BAT volume and activity determined by a combination of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography scan. Cardiorespiratory fitness was associated with neither the BAT volume nor BAT activity (P ≥ 0.05). However, handgrip strength with respect to lean body mass was positively (though weakly) associated with BAT activity as represented by the 18F-FDG mean standardised uptake value (SUV) (β = 3.595, R2 = 0.039, P = 0.031) and SUVpeak value (β = 15.314, R2 = 0.037, P = 0.035). The above relationships remained after adjusting for several confounders. No other associations were found. Handgrip strength with respect to lean body mass is positively associated with BAT activity (SUVmean and SUVpeak) in young adults after exposure to cold - but only weakly. Further studies are needed to reveal the relationship between muscular fitness and human BAT characteristics.This study was supported by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Retos de la Sociedad (DEP2016-79512-R) and European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365 and FPU14/04172), the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES) - and Plan Propio de Investigación 2018 - Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF: SOMM17/6107/UGR)

Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice

Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3−/− mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3−/− mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3−/− mice. Lipid metabolism disorders in Sik3−/− mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice

Drivers of circulation in a fringing coral reef embayment: a wave-flow coupled numerical modeling study of Hanalei Bay, Hawaii

A coupled wave-circulation numerical model of Hanalei Bay, Hawaii, was constructed to investigate controls on nearshore hydrodynamics and overall circulation of a bathymetrically-complex coral reef embayment that is exposed to large waves and river floods several times per annum. The model was calibrated using in situ data representative of the two conditions that dominate the region's wave climate: one associated with local trade winds and associated trade-wind waves, and the other with distant-source episodic large swells. The model results were improved by including spatially-varying hydrodynamic bed roughness and making the semi-empirical wave-breaking parameter dependent on incident wave steepness and reef slope. During trade-wind conditions, circulation was primarily wind-driven and volume flux-based flushing times of the bay were on the order of 35 h. Under the episodic swell conditions, circulation were dominated by wave-driven flows and flushing times decreased to as little as 2 h. The vigorous hydrodynamics that occur during the upper 10% most energetic swell conditions indicate that only a few (0–10) events each year are likely capable of exporting significant volumes of sediment from the bay. Like many fringing reef areas backed by steep-sided watersheds on tropical and sub-tropical high islands worldwide, Hanalei Bay receives high episodic fluvial sediment load during a similarly low number of flood events. These similarly episodic but decoupled processes of sediment delivery and removal identified here suggest that the water quality and sedimentary environment of Hanalei Bay and similar linked watershed-reef systems are sensitive to changes in annual storm frequency and intensity

Systematic Study of the Interaction Between VIV Centres and LnIII Ions in Well Defined {VIV2LnIII}{AsIIIW9O33}2 Sandwich-Type Clusters: Part 2

Merca A, Schnack J, v. Slageren J, et al. Systematic Study of the Interaction Between VIV Centres and LnIII Ions in Well Defined {VIV2LnIII}{AsIIIW9O33}2 Sandwich-Type Clusters: Part 2. J. Cluster Sci. 2013;24:979-988

Probing the magnetic moments of [Mn^III₆Cr^III]³⁺ single-molecule magnets - A cross comparison of XMCD and spin-resolved electron spectroscopy

Helmstedt A, Dohmeier N, Müller N, et al. Probing the magnetic moments of $[Mn^{III} _6Cr ^{III}] ^{3+}$single-molecule magnets - A cross comparison of XMCD and spin-resolved electron spectroscopy. J. Electron. Spectrosc. Relat. Phenom. 2015;198:12-19

The local magnetic properties of [Mn^III₆ Cr^III]³⁺ and [Fe^III₆ Cr^III]³⁺ single-molecule magnets deposited on surfaces studied by spin-polarized photoemission and XMCD with circularly polarized synchrotron radiation

Heinzmann U, Helmstedt A, Dohmeier N, et al. The local magnetic properties of [(Mn6CrIII)-Cr-III](3+) [ and [(Fe6CrIII)-Cr-III](3+) single-molecule magnets deposited on surfaces studied by spin-polarized photoemission and XMCD with circularly polarized synchrotron radiation. In: Collisions involving condensed matter [Abstracts]. Journal of Physics Conference Series. Vol 488. Bristol: Iop Publishing; 2014.It is demonstrated that local magnetic moments of single molecule magnets (SMM) normally studied by XMCD at very low temperatures and high magnetic fields can be measured by means of spin-resolved electron emission in the paramagnetic phase at room temperature by use of circularly polarized radiation

Glycogen synthase kinase-3 regulates cigarette smoke extract- and IL-1 beta-induced cytokine secretion by airway smooth muscle

Baarsma HA, Meurs H, Halayko AJ, Menzen MH, Schmidt M, Kerstjens HA, Gosens R. Glycogen synthase kinase-3 regulates cigarette smoke extract- and IL-1 beta-induced cytokine secretion by airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 300: L910-L919, 2011. First published March 18, 2011; doi:10.1152/ajplung.00232.2010.-Glycogen synthase kinase-3 (GSK-3) is a constitutively active kinase that regulates multiple signaling proteins and transcription factors involved in inflammation. Its role in inflammatory lung diseases, including chronic obstructive pulmonary disease (COPD), is largely unknown. We investigated the role of GSK-3 in the secretion of chemokines and growth factors by human airway smooth muscle cells after exposure to cigarette smoke extract (CSE) or interleukin-1 beta (IL-1 beta), important factors involved in the development of COPD. Cultured human airway smooth muscle cells were exposed to increasing concentrations of CSE (1-15%) and IL-1 beta (0.01-1.0 ng/ml), which induced the secretion of VEGF-A and IL-8, whereas eotaxin secretion was induced by IL-1 beta only. Inhibition of GSK-3 by the selective inhibitor SB216763 or CHIR/CT99021 attenuated the cytokine and growth factor release induced by CSE and/or IL-1 beta, without affecting the basal release. Secretion of the cytokines by airway smooth muscle partially depends on NF-kappa B signaling, and GSK-3 has been implicated in regulating multiple steps in activating the NF-kappa B signaling pathway. IL-1 beta treatment induced degradation of the NF-kappa B inhibitory protein I kappa-B alpha followed by nuclear translocation and DNA binding of p65 NF-kappa B, which were unaffected by inhibition of GSK-3. However, induction of NF-kappa B-dependent transcriptional activity by IL-1 beta and CSE was largely reduced upon GSK-3 inhibition by SB216763. Collectively, we demonstrate that CSE and IL-1 beta activate airway smooth muscle cells to secrete the proinflammatory cytokines IL-8, eotaxin, and VEGF-A. Furthermore, we show that GSK-3 regulates the release of these cytokines induced by CSE and IL-1 beta by promoting NF-kappa B-dependent gene transcription

Pharmacological inhibition of GSK-3 in a guinea pig model of LPS-induced pulmonary inflammation: II. Effects on skeletal muscle atrophy

Background: Chronic obstructive pulmonary disease (COPD) is accompanied by pulmonary inflammation and associated with extra-pulmonary manifestations, including skeletal muscle atrophy. Glycogen synthase kinase-3 (GSK-3) has been implicated in the regulation of muscle protein-and myonuclear turnover; two crucial processes that determine muscle mass. In the present study we investigated the effect of the selective GSK-3 inhibitor SB216763 on muscle mass in a guinea pig model of lipopolysaccharide (LPS)-induced pulmonary inflammation-associated muscle atrophy. Methods: Guinea pigs were pretreated with either intranasally instilled SB216763 or corresponding vehicle prior to each LPS/saline challenge twice weekly. Pulmonary inflammation was confirmed and indices of muscle mass were determined after 12 weeks. Additionally, cultured skeletal muscle cells were incubated with tumor necrosis factor a (TNF-alpha) or glucocorticoids (GCs) to model the systemic effects of pulmonary inflammation on myogenesis, in the presence or absence of GSK-3 inhibitors. Results: Repeated LPS instillation induced muscle atrophy based on muscle weight and muscle fiber cross sectional area. Intriguingly, GSK-3 inhibition using SB216763 prevented the LPS-induced muscle mass decreases and myofiber atrophy. Indices of protein turnover signaling were unaltered in guinea pig muscle. Interestingly, inhibition of myogenesis of cultured muscle cells by TNF-alpha or synthetic GCs was prevented by GSK-3 inhibitors. Conclusions: In a guinea pig model of LPS-induced pulmonary inflammation, GSK-3 inhibition prevents skeletal muscle atrophy without affecting pulmonary inflammation. Resistance to inflammation-or GC-induced impairment of myogenic differentiation, imposed by GSK-3 inhibition, suggests that sustained myogenesis may contribute to muscle mass maintenance despite persistent pulmonary inflammation. Collectively, these results warrant further exploration of GSK-3 as a potential novel drug target to prevent or reverse muscle wasting in COPD