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Plasma growth differentiation factor-15 (GDF-15) levels increase with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) but the underlying mechanism remains poorly defined. Using male mouse models of obesity and MASLD, and biopsies from carefully-characterized patients regarding obesity, type 2 diabetes (T2D) and MASLD status, we identify adipose tissue (AT) as the key source of GDF-15 at onset of obesity and T2D, followed by liver during the progression towards metabolic dysfunction-associated steatohepatitis (MASH). Obesity and T2D increase GDF15 expression in AT through the accumulation of macrophages, which are the main immune cells expressing GDF15. Inactivation of Gdf15 in macrophages reduces plasma GDF-15 concentrations and exacerbates obesity in mice. During MASH development, Gdf15 expression additionally increases in hepatocytes through stress-induced TFEB and DDIT3 signaling. Together, these results demonstrate a dual contribution of AT and liver to GDF-15 production in metabolic diseases and identify potential therapeutic targets to raise endogenous GDF-15 levels., (© 2024. The Author(s).)

Bile acids (BAs) improve metabolism and exert anti-obesity effects through the activation of the Takeda G protein-coupled receptor 5 (TGR5) in peripheral tissues. TGR5 is also found in the brain hypothalamus, but whether hypothalamic BA signaling is implicated in body weight control and obesity pathophysiology remains unknown. Here we show that hypothalamic BA content is reduced in diet-induced obese mice. Central administration of BAs or a specific TGR5 agonist in these animals decreases body weight and fat mass by activating the sympathetic nervous system, thereby promoting negative energy balance. Conversely, genetic downregulation of hypothalamic TGR5 expression in the mediobasal hypothalamus favors the development of obesity and worsens established obesity by blunting sympathetic activity. Lastly, hypothalamic TGR5 signaling is required for the anti-obesity action of dietary BA supplementation. Together, these findings identify hypothalamic TGR5 signaling as a key mediator of a top-down neural mechanism that counteracts diet-induced obesity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Many investigations have been carried out in order to develop models which allow the understanding of complex physical processes involved in urban flooding. The modelling of the interactions between overland flows on streets and flooding flows from rivers and sewer networks is one of the main objectives of recent and current research programs in hydraulics and urban hydrology. However, the modelling of the discharge distribution in the street network with crossroad needs further research due to the complexity of the flow through junctions. This paper outlines the ability of the improved one-dimensional CANOE software to simulate the street flows through the virtual network (developed under the Hy(2)Ville French National project framework) with several cross-roads. The improvements are done by adding in CANOE the energy losses coefficients deriving from the calibration phase based on the experimental study of the flow through small scale physical model of cross-road channels. Comparisons between 1D and 2D simulated distribution of discharges through the virtual network show a good agreement for the global distribution. However, large differences are observed focusing on the individual cross-road intersections in the virtual network.

Up to now, most investigations on the dependency of the fluid flow patterns and performance of waste stabilisation ponds (WSPs) on wind speed and direction and pond layout have been performed using 2D and 3D CFD steady state isothermal models. 3D non steady state models integrating thermal processes and boundary conditions taking into account the full influence of meteorological factors are likely to provide more realistic predictions of WSP performance. Such modelling was undertaken for 4 pond layouts, 2 without baffles and 2 with baffles. Wind speed and direction were kept constant throughout each simulation while other meteorological forcings were derived from field measurements. Twelve wind directions and 2, 4 and 6 m s(-1) wind speeds were considered for each WSP layout. Simulations allowed verifying that the pond performance is dependent on the wind direction and velocity, that baffles may improve WSP performance and that the addition of well-designed baffles has the advantage of reducing its sensitivity to the wind.

As treatment processes are kinetic-dependent, a consistent description of water residence times is essential to the prediction of waste stabilization ponds performance. A physically-based 3D transient CFD model simulating the water velocity, temperature and concentration fields as a function of all influent meteorological factors--wind speed and direction, solar radiation, air temperature and relative humidity--was used to identify the relationships between the meteorological conditions and the hydrodynamic patterns and water residence times distributions in a polishing pond. The required meteorological data were recorded on site and water temperatures recorded at 10 sampling sites for 141 days. Stratification events appear on very calm days for wind speeds lower than 3 m s(-1) and on sunny days for wind speeds lower than 5 m s(-1). De-stratification is related to two mixing processes: nightly convection cells and global mixing patterns. Numerical tracer experiments show that the results of the flow patterns can be evaluated using the dispersed flow regime approximation and, for wind speeds exceeding 6 m s(-1), the completely stirred tank reactor assumption.

Many investigations have been carried out in order to develop models which allow the linking of complex physical processes involved in urban flooding. The modelling of the interactions between overland flows on streets and flooding flows from rivers and sewer networks is one of the main objectives of recent and current research programs in hydraulics and urban hydrology. This paper outlines the original one-dimensional linking of heavy rainfall-runoff in urban areas and flooding flows from rivers and sewer networks under the RIVES project framework (Estimation of Scenario and Risks of Urban Floods). The first part of the paper highlights the capacity of Canoe software to simulate the street flows. In the second part, we show the original method of connection which enables the modelling of interactions between processes in urban flooding. Comparisons between simulated results and the results of Despotovic et al. or Gomez & Mur show a good agreement for the calibrated one-dimensional connection model. The connection operates likes a manhole with the orifice/weir coefficients used as calibration parameters. The influence of flooding flows from river was taken into account as a variable water depth boundary condition.