Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle

Fatty liver index associates with relative sarcopenia and GH/ IGF- 1 status in obese subjects

Recently the association between hepatic steatosis and sarcopenia has been described. GH/IGF-1 axis has been postulated to play a role in linking fatty liver and low muscle mass. The aim of our study was to explore the association between fatty liver index, sarcopenic obesity, insulin sensitivity, and GH/IGF-1 status

Exploring the multiple effects of the invasive alien robinia tree: a PhD project presentation

The poster explains the background, research questions and objectives and methods of the PhD study on black locust (Robinia pseudoacacia) funded by the Linda Scattolin J:ROBIN project (2016-2019)

3_D modeling using TLS and GPR techniques to characterize above and below-ground wood distribution in pyroclastic deposits along the Blanco River (Chilean Patagonia)

To date, the study of in-stream wood in rivers has been focused mainly on quantifying wood pieces deposited above the ground. However, in some particular river systems, the presence of buried dead wood can also represent an important component of wood recruitment and budgeting dynamics. This is the case of the Blanco River (Southern Chile) severely affected by the eruption of Chait\ue9n Volcano occurred between 2008 and 2009. The high pyroclastic sediment deposition and transport affected the channel and the adjacent forest, burying wood logs and standing trees. The aim of this contribution is to assess the presence and distribution of wood in two study areas (483 m2 and 1989 m2, respectively) located along the lower streambank of the Blanco River, and covered by thick pyroclastic deposition up to 5 m. The study areas were surveyed using two different devices, a Terrestrial Laser Scanner (TLS) and a Ground Penetrating Radar (GPR). The first was used to scan the above surface achieving a high point cloud density ( 48 2000 points m-2) which allowed us to identify and measure the wood volume. The second, was used to characterize the internal morphology of the volcanic deposits and to detect the presence and spatial distribution of buried wood up to a depth of 4 m. Preliminary results have demonstrated differences in the numerousness and volume of above wood between the two study areas. In the first one, there were 43 wood elements, 33 standing trees and 10 logs, with a total volume of 2.96 m3 (109.47 m3 km-1), whereas the second one was characterized by the presence of just 7 standing trees and 11 wood pieces, for a total amount of 0.77 m3 (7.73 m3 km-1). The dimensions of the wood elements vary greatly according to the typology, standing trees show the higher median values in diameter and length (0.15 m and 2.91 m, respectively), whereas the wood logs were smaller (0.06 m and 1.12 m, respectively). The low dimensions of deposited wood can be probably connected to their origin, suggesting that these elements were generated by toppling and breaking of surrounding dead trees. Results obtained with the GPR confirm the ability of this instrument to localize the presence and distribution of buried wood. From the 3- D analysis it was possible to assess the spatial distribution and to estimate, as first approach, the volume of the buried wood which represents approximately 0.04% of the entire volcanic deposit. Further analysis will focus on additional GPR calibration with different wood sizes for a more accurate estimation of the volume. The knowledge of the overall wood amount stored in a fluvial system that can be remobilized over time, represent an essential factor to ensure better forest and river management actions

Disability, Physical Inactivity, and Impaired Health-Related Quality of Life Are Not Different in Metabolically Healthy vs. Unhealthy Obese Subjects

BACKGROUND: Obesity represents a major health hazard, affecting morbidity, psychological status, physical functionality, quality of life, and mortality. The aim of the present study was to explore the differences between metabolically healthy (MHO) and metabolically unhealthy (MUO) obese subjects with regard to physical activity, disability, and health-related quality of life (HR-QoL). METHODS: All subjects underwent a multidimensional evaluation, encompassing the assessment of body composition, metabolic biomarkers and inflammation, physical activity level (IPAQ questionnaire), disability (TSD-OC test), and HR-QoL (SF-36 questionnaire). MHO and MUO were defined based on the absence or the presence of the metabolic syndrome, respectively. RESULTS: 253 subjects were included (54 men and 199 women; age: 51.7 ± 12.8 vs. 50.3 ± 11.7 years, p = 0.46; BMI: 38.1 ± 5.7 vs. 38.9 ± 6.7 kg/m², p = 0.37). No significant difference was observed in body composition. There was no difference between MHO and MUO considering inflammation (hs-CRP: 6517.1 ± 11,409.9 vs. 5294.1 ± 5612.2 g/L; p = 0.37), physical inactivity (IPAQ score below 3000 METs-min/week in 77.6% of MHO vs. 80% of MUO subjects; p = 0.36), obesity-related disability (TSD-OC score > 33%, indicating a high level of obesity-related disability, in 20.2% of MHO vs. 26.5% of MUO subjects; p = 0.28), and the HR-QoL (SF-36 total score: 60 ± 20.8 vs. 62.8 ± 18.2, p = 0.27). DISCUSSION AND CONCLUSION:The metabolic comorbidity and the impairment of functional ability and psycho-social functioning may have a different timing in the natural history of obesity. Alterations in the physical activity level and mobility disabilities may precede the onset of metabolic abnormalities. (Trial registration 2369 prot 166/12-registered 23 February 2012; Amendment 223/14-registered 13 February 2014)

Peripheral Arterial Tonometry to Measure the Effects of Vardenafil on Sympathetic Tone in Men with Lifelong Premature Ejaculation

To elucidate whether adrenergic overtone is involved in the pathophysiology of men with lifelong (LL) premature ejaculation (PE), we investigated differences in reactive hyperemia index (RHI) responses by using peripheral arterial tonometry (PAT). 20 men with LL-PE (18–40 years) were enrolled in an 8-week, double-blind, placebo-controlled, crossover study and compared with 10 age-matched controls without LL-PE. Primary endpoints were PAT modifications induced by vardenafil 10 mg on demand. Secondary endpoints were the improvement in intravaginal ejaculatory latency time (IELT) as measured by the stopwatch technique and variations in anxiety scores at Stai-X1 for state-anxiety and Stai-X2 for trait-anxiety. At baseline, men with LL-PE showed higher RHI variation (), Stai-X1 and Stai X2 scores (, resp.), and prolactin levels () compared with controls. Vardenafil treatment markedly reduced RHI variation in men with LL-PE () when compared with placebo. Mean changes in geometric IELT were higher after taking vardenafil (0.6 ± 0.3 versus 4.5 ± 1.1 min, ) when compared with placebo. STAI-X1 and STAI-X2 scores fell within the normal range after treatment with vardenafil (). Vardenafil was an effective treatment in men with LL-PE; improvements of IELT may be due to increased NO production which is able to reduce adrenergic overactivity and anxiety levels

The decline in muscle strength and muscle quality in relation to metabolic derangements in adult women with obesity

Background & aims: The metabolic and functional characteristics related to sarcopenic obesity have not been thoroughly explored in the earlier stages of the aging process. The aim of the present study was to examine the phenotype of sarcopenic obesity, in terms of lean body mass, muscle strength and quality, in adult women with and without the Metabolic Syndrome (MetS), and its relationship with the features of myosteatosis. Methods: Study participants were enrolled at the Sapienza University, Rome, Italy. Body composition was assessed by DXA. The Handgrip strength test (HGST) was performed. HGST was normalized to arm lean mass to indicate muscle quality; intermuscular adipose tissue (IMAT) and intramyocellular lipid content (IMCL) were measured by magnetic resonance imaging and spectroscopy, as indicators of myosteatosis. Different indices of sarcopenia were calculated, based on appendicular lean mass (ALM, kg) divided by height squared, or weight. The NCEP-ATPIII criteria were used to diagnose the MetS. HOMA-IR was calculated. The physical activity level (PAL) was assessed through the IPAQ questionnaire. Results: 54 women (age: 48 ± 14 years, BMI: 37.9 ± 5.4 kg/m 2 ) were included. 54% had the MetS (metabolically unhealthy, MUO). HGST/arm lean mass was lower in MUO women than women without the MetS (6.3 ± 1.8 vs. 7.8 ± 1.6, p = 0.03). No differences emerged in terms of absolute ALM (kg) or other indices of sarcopenia (ALM/h 2 or ALM/weight) between metabolically healthy (MHO) vs. MUO women (p > 0.05). Muscle quality was negatively associated with HOMA-IR (p = 0.02), after adjustment for age, body fat, hs-CRP levels, and PAL. IMAT, but not IMCL, was significantly higher in obese women with the MetS compared to women without the MetS (p > 0.05). No association emerged between HGST/arm lean mass and IMAT or IMCL when HOMA-IR was included in the models. Conclusion: Insulin resistance, and not sarcopenia or myosteatosis per se, was associated with muscle weakness, resulting in the phenotype of “dynapenic obesity” in middle-aged women with the metabolic syndrome

Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity

Background and aim: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. Methods and results: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (rho = -0.350, P = 0.005; rho = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (beta = -0.352, P = 0.016). Conclusions: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved

Lithium limits trimethyltin-induced cytotoxicity and proinflammatory response in microglia without affecting the concurrent autophagy impairment

Trimethyltin (TMT) is a highly toxic molecule present as an environmental contaminant causing neurodegeneration particularly of the limbic system both in humans and in rodents. We recently described the occurrence of impairment in the late stages of autophagy in TMT-intoxicated astrocytes. Here we show that similarly to astrocytes also in microglia, TMT induces the precocious block of autophagy indicated by the accumulation of the autophagosome marker, microtubule associated protein light chain 3. Consistent with autophagy impairment we observe in TMT-treated microglia the accumulation of p62/SQSTM1, a protein specifically degraded through this pathway. Lithium has been proved effective in limiting neurodegenerations and, in particular, in ameliorating symptoms of TMT intoxication in rodents. In our in vitro model, lithium displays a pro-survival and anti-inflammatory action reducing both cell death and the proinflammatory response of TMT-treated microglia. In particular, lithium exerts these activities without reducing TMT-induced accumulation of light chain 3 protein. In fact, the autophagic block imposed by TMT is unaffected by lithium administration. These results are of interest as defects in the execution of autophagy are frequently observed in neurodegenerative diseases and lithium is considered a promising therapeutic agent for these pathologies. Thus, it is relevant that this cation can still maintain its pro-survival and anti-inflammatory role in conditions of autophagy bloc

Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin

Autophagy is a lysosomal catabolic route for protein aggregates and damaged organelles which in different stress conditions, such as starvation, generally improves cell survival. An impairment of this degradation pathway has been reported to occur in many neurodegenerative processes. Trimethyltin (TMT) is a potent neurotoxin present as an environmental contaminant causing tremors, seizures and learning impairment in intoxicated subjects. The present data show that in rat primary astrocytes autophagic vesicles (AVs) appeared after few hours of TMT treatment. The analysis of the autophagic flux in TMT-treated astrocytes was consistent with a block of the late stages of autophagy and was accompanied by a progressive accumulation of the microtubule associated protein light chain 3 (LC3) and of p62/SQSTM1. Interestingly, an increased immunoreactivity for p62/SQSTM1 was also observed in hippocampal astrocytes detected in brain slices of TMT-intoxicated rats. The time-lapse recordings of AVs in EGFP-mCherry-LC3B transfected astrocytes demonstrated a reduced mobility of autophagosomes after TMT exposure respect to control cells. The observed block of the autophagic flux cannot be overcome by known autophagy inducers such as rapamycin or 0.5mM lithium. Although ineffective when used at 0.5mM, lithium at higher concentrations (2mM) was able to protect astrocyte cultures from TMT toxicity. This effect correlated well with its ability to determine the phosphorylation/inactivation of glycogen kinase synthase-3β (GSK-3β)