Obesity and type 2 diabetes are characterized by decreased insulin sensitivity, elevated concentrations of free fatty acids (FFAs), and increased macrophage infiltration in adipose tissue (AT). Here, we show that FFAs can cause activation of RAW264.7 cells primarily via the JNK signaling cascade and that TLR2 and TLR4 are upstream of JNK and help transduce FFA proinflammatory signals. We also demonstrate that F4/80+CD11b+CD11c+ bone marrow-derived dendritic cells (BMDCs) have heightened proinflammatory activity compared with F4/80+CD11b+CD11c- bone marrow-derived macrophages and that the proinflammatory activity and JNK phosphorylation of BMDCs, but not bone marrow-derived macrophages, was further increased by FFA treatment. F4/80+CD11b+CD11c+ cells were found in AT, and the proportion and number of these cells in AT is increased in ob/ob mice and by feeding wild type mice a high fat diet for 1 and 12 weeks. AT F4/80+CD11b+CD11c+ cells express increased inflammatory markers compared with F4/80+CD11b+CD11c- cells, and FFA treatment increased inflammatory responses in these cells. In addition, we found that CD11c expression is increased in skeletal muscle of high fat diet-fed mice and that conditioned medium from FFA-treated wild type BMDCs, but not TLR2/4 DKO BMDCs, can induce insulin resistance in L6 myotubes. Together our results show that FFAs can activate CD11c+ myeloid proinflammatory cells via TLR2/4 and JNK signaling pathways, thereby promoting inflammation and subsequent cellular insulin resistance.
1 July 2018 in Transportation Research Part D: Transport and Environment
California, a pioneer in EV adoption, has enacted ambitious electric vehicle (EV) policies that will generate a large burden on the state’s electric distribution system. We investigate the statewide impact of uncontrolled EV charging on the electric distribution networks at a large scale and high granularity, by employing an EV charging profile projection that combines travel demand model, EV adoption model, and real-world EV charging data. We find a substantial need for infrastructure upgrades in 50% of feeders by 2035, and 67% of feeders by 2045. The distribution system across California must upgrade its capacity by 25 GW by 2045, corresponding to a cost between $6 and $20 billion. While the additional infrastructure cost drives the electricity price up, it is offset by the downward pressure from the growth of total electricity consumption and leads to a reduction in electricity rate between $0.01 and $0.06/kWh by 2045. We also find that overloading conditions are highly diverse spatially, with feeders in residential areas requiring twice as much upgrade compared to commercial areas. Our study provides a framework for evaluating EVs’ impact on the distribution grid and indicates the potential to reduce infrastructure upgrade costs by shifting home-charging demand. The imminent challenges confronting California serve as a microcosm of the forthcoming obstacles anticipated worldwide due to the prevailing global trend of EV adoption.