Project description:Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets led to hyperphagia, obesity and reduced lifespan. These effects were not due to elevated BCAA per se or hepatic mTOR activation, but rather the shift in balance between dietary BCAAs and other AAs, notably tryptophan and threonine. Increasing the ratio of BCAAs to these AAs resulted in hyperphagia and was linked to central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averted the health costs of a high BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes were not due to intrinsic toxicity; rather, to hyperphagia driven by AA imbalance.
Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery.
There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.
Project description:N-acyl amino acid methyl esters (NAMEs), which are structurally similar to the signalling compounds N-acyl homoserine lactones (AHLs), have been identified in culture extracts of Roseovarius tolerans EL-164. However, previous studies have shown that NAMEs do not participate in AHL-mediated signalling and thus their ecological role remains unclear. To enable dose-dependent bioactivity-testing of NAMEs, we have established a quantification method for NAMEs. The concentrations determined for the major NAMEs produced by EL 164, C16:1- and C17:1-NAME, ranged between 0.7-5.7 mg L-1 and 5.3-86.4 µg L-1, respectively. We observed opposing production patterns for NAMEs and AHLs, with a continuously increasing NAME production during exponential growth and an accumulation in the stationary phase. We further conducted a spike-in experiment, using the previously determined metabolite concentrations. By comparing the transcriptomes of pre- and post-NAME or AHL spikes, we identified distinct impacts on gene expression patterns. Different genetic neighbourhoods were significantly up- or downregulated in NAME and AHL-spiked cultures. Yet no synergetic effect was observed. These findings exemplify the broad application range of dose-dependent testing and highlight the different biological activities of NAMEs and AHLs.