A constellation of metabolic disorders, including obesity, dysregulated lipids, and elevations in blood glucose levels, has been associated with cardiovascular disease and diabetes. Analysis of data from recently published genome-wide association studies (GWAS) demonstrated that reduced-function polymorphisms in the organic cation transporter, OCT1 (SLC22A1), are significantly associated with higher total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels and an increased risk for type 2 diabetes mellitus, yet the mechanism linking OCT1 to these metabolic traits remains puzzling. Here, we show that OCT1, widely characterized as a drug transporter, plays a key role in modulating hepatic glucose and lipid metabolism, potentially by mediating thiamine (vitamin B1) uptake and hence its levels in the liver. Deletion of Oct1 in mice resulted in reduced activity of thiamine-dependent enzymes, including pyruvate dehydrogenase (PDH), which disrupted the hepatic glucose–fatty acid cycle and shifted the source of energy production from glucose to fatty acids, leading to a reduction in glucose utilization, increased gluconeogenesis, and altered lipid metabolism. In turn, these effects resulted in increased total body adiposity and systemic levels of glucose and lipids. Importantly, wild-type mice on thiamine deficient diets (TDs) exhibited impaired glucose metabolism that phenocopied Oct1 deficient mice. Collectively, our study reveals a critical role of hepatic thiamine deficiency through OCT1 deficiency in promoting the metabolic inflexibility that leads to the pathogenesis of cardiometabolic disease.

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Drawing on current international industrial ecology thinking and experiences with Australian initiatives, this article critically overviews the current status of industrial ecology in Australia and examines the barriers and potential strategies to realise greater uptake and application of the concept. The analysis is conducted across three categories: heavy industrial areas (including Kwinana and Gladstone), mixed industrial parks (Wagga Wagga and Port Melbourne), and waste exchange networks, and identifies the past and future significance of seven different types of barriers-regulation, information, community, economic, technical, cooperation and trust, commitment to sustainable development-for each of the three categories. The outcomes from this analysis highlight that regulation, information, and economic barriers for heavy industrial area and mixed industrial parks, and economic and technical barriers for waste exchange networks are the current and future focus for industrial ecology applications in Australia. These findings appear to be consistent with recently published frameworks and learnings. The authors propose key questions that could enhance greater adoption of industrial ecology applications in Australia and acknowledge that international research and experiences,

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