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Summary: Despite medical advances, there remains an unmet need for better treatment of obesity. Itaconate, a product of the decarboxylation of the tricarboxylic acid cycle intermediate cis-aconitate, plays a regulatory role in both metabolism and immunity. Here, we show that itaconate, as an endogenous compound, counteracts high-fat-diet (HFD)-induced obesity through leptin-independent mechanisms in three mouse models. Specifically, itaconate reduces weight gain, reverses hyperlipidemia, and improves glucose tolerance in HFD-fed mice. Additionally, itaconate enhances energy expenditure and the thermogenic capacity of brown adipose tissue (BAT). Unbiased proteomic analysis reveals that itaconate upregulates key proteins involved in fatty acid oxidation and represses the expression of lipogenic genes. Itaconate may provoke a major metabolic reprogramming by inducing fatty acid oxidation and suppression of fatty acid synthesis in BAT. These findings highlight itaconate as a potential activator of BAT-mediated thermogenesis and a promising candidate for anti-obesity therapy.

The diverse applications of various tissues of Polygonum Multiflorum (PM) encompass the use of its leaf and bud as tea and vegetables, as well as the utilization of its expanded root tubers and caulis as medicinal substances. However, previous studies in the field of metabolomics have primarily focused on the medicinal properties of PM. In order to investigate the potential for broader applications of other tissues within PM, a metabolomic analysis was conducted for the first time using UPLC-Q-TOF-MS/MS on 15 fresh PM tissues. A total of 231 compounds, including newly discovered compounds such as torosachrysone and dihydro-trihydroxystilbene acid derivatives, were identified within PM. Through clustering analysis, the PM tissues were categorized into edible and medicinal parts, with edible tissues exhibiting higher levels of phenolic acids, organic acids, and flavonoids, while the accumulation of quinones, dianthrones, stilbenes, and xanthones was observed in medicinal tissues. Comparative analysis demonstrated the potential application of discarded tissues, such as unexpanded root tuber (an industrial alternative to expanded root tuber) and young caulis (with edible potential). Moreover, the quantification of representative metabolites indicated that flowers and buds contained significant amounts of flavonoids or phenolic acids, suggesting their potential as functional food. Additionally, the edible portion of PM exhibited a high content of quercitrin, ranging from 0.59 to 10.37 mg/g. These findings serve as a valuable point of reference for the expanded utilization of PM tissues, thereby mitigating resource waste in this plant.