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Background and objectives Obesity is one of the major drivers of heart failure with preserved ejection fraction (HFpEF). Endothelial cells (EC) have an important barrier function including the control of lipid transport from the coronary circulation to the myocardium. This EC lipid transport involves, in addition to fast transcellular transport, processes of EC-lipogenesis and -lipolysis, and is likely involved in the development of cardiac lipid accumulation in obese phenotypes of HFpEF. In order to determine the role of EC lipid metabolism/transport in HFpEF, we generated mice with an EC-specific deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme of lipolysis, and subjected these mice to a hypertensive-obese two-hit HFpEF model. Methods and results Inducible endothelial-specific ATGL knockout (ecATGL-KO) mice were generated by crossbreeding Atgl fl/fl mice with Cdh5(PAC)-CreERT2 mice. For the induction of HFpEF, mice received a high fat diet (HFD, 60% kcal from fat) and L-NAME for 15 weeks, while control animals (Ctrl) received low fat diet (LFD, 10% kcal from fat) and water, as previously described. To analyse cardiac function, standard and speckle-tracking echocardiography were performed. After 15 weeks, Cre− littermates (wild type, wt) with HFpEF developed obesity and hypertension (body weight: wt-Ctrl: 33.8±2.5g vs. wt-HFpEF: 45.1±4.4g, p Conclusion This study demonstrates that the lack of ATGL in ECs attenuates the development of HFpEF. Enhanced lipid droplet accumulation in coronary ECs in the absence of ATGL may protect the myocardium from lipid overload, as seen in obese phenotypes of HFpEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Einstein Foundation Berlin;DZHK (German Centre for Cardiovascular Research), partner site Berlin;DFG (Deutsche Forschungsgemeinschaft)

Future changes in river runoff will impact many sectors such as agriculture, energy production, or ecosystems. Here, we study changes in the seasonality, frequency, and magnitude of moderate low and high flows and their time of emergence. The time of emergence indicates the timing of significant changes in the flow magnitudes. Daily runoff is simulated for 93 Swiss catchments for the period 1981–2099 under Representative Concentration Pathway 8.5 with 20 climate model chains from the most recent transient Swiss Climate Change Scenarios. In the present climate, annual low flows typically occur in the summer half-year in lower-lying catchments ( m a.s.l.) and in the winter half-year in Alpine catchments (>1500 m a.s.l.). By the end of the 21st century, annual low flows are projected to occur in late summer and early autumn in most catchments. This indicates that decreasing precipitation and increasing evapotranspiration in summer and autumn exceed the water contributions from other processes such as snowmelt and glacier melt. In lower-lying catchments, the frequency of annual low flows increases, but their magnitude decreases and becomes more severe. In Alpine catchments, annual low flows occur less often and their magnitude increases. The magnitude of seasonal low flows is projected to decrease in the summer half-year in most catchments and to increase in the winter half-year in Alpine catchments. Early time of emergence is found for annual low flows in Alpine catchments in the 21st century due to early changes in low flows in the winter half-year. In lower-lying catchments, significant changes in low flows emerge later in the century. Annual high flows occur today in lower-lying catchments in the winter half-year and in Alpine catchments in the summer half-year. Climate change will change this seasonality mainly in Alpine catchments with a shift towards earlier seasonality in summer due to the reduced contribution of snowmelt and glacier melt in summer. Annual high flows tend to occur more frequent, and their magnitude increases in most catchments except some Alpine catchments. The magnitude of seasonal high flows in most catchments is projected to increase in the winter half-year and to decrease in the summer half-year. However, the climate model agreement on the sign of change in moderate high flows is weak.

Assessments of climate change impacts on runoff regimes are essential to climate change adaptation and mitigation planning. Changing runoff regimes and thus changing seasonal patterns of water availability strongly influence various economic sectors such as agriculture, energy production, and fishery and also affect river ecology. In this study, we use new transient hydrological scenarios driven by the most up-to-date local climate projections for Switzerland, the Swiss Climate Change Scenarios. These provide detailed information on changes in runoff regimes and their time of emergence for 93 rivers in Switzerland under three Representative Concentration Pathways (RCPs): RCP2.6, RCP4.5, and RCP8.5. These transient scenarios also allow changes to be framed as a function of global mean temperature. The new projections for seasonal runoff changes largely confirm the sign of changes in runoff from previous hydrological scenarios with increasing winter runoff and decreasing summer and autumn runoff. Spring runoff is projected to increase in high-elevation catchments and to decrease in lower-lying catchments. Despite the increases in winter and some increases in spring, the annual mean runoff is projected to decrease in most catchments. Compared to lower-lying catchments, runoff changes in high-elevation catchments (above 1500 m a.s.l.) are larger in winter, spring, and summer due to the large influence of reduced snow accumulation and earlier snowmelt and glacier melt. The changes in runoff and the agreement between climate models on the sign of change both increase with increasing global mean temperatures and higher-emission scenarios. This amplification highlights the importance of climate change mitigation. The time of emergence is the time when the climate signal emerges significantly from natural variability. Under RCP8.5, times of emergence were found early, before the period 2036–2065, in winter and summer for catchments with mean altitudes above 1500 m a.s.l. Significant changes in catchments below 1500 m a.s.l. emerge later in the century. Not all catchments show significant changes in the distribution of seasonal means; thus, no time of emergence could be determined in these catchments. Furthermore, the significant changes of seasonal mean runoff are not persistent over time in some catchments due to nonlinear changes in runoff.