Activation of GPR81 by lactate drives tumour-induced cachexia.

Cachexia affects 50-80% of patients with cancer and accounts for 20% of cancer-related death, but the underlying mechanism driving cachexia remains elusive. Here we show that circulating lactate levels positively correlate with the degree of body weight loss in male and female patients suffering from cancer cachexia, as well as in clinically relevant mouse models. Lactate infusion per se is sufficient to trigger a cachectic phenotype in tumour-free mice in a dose-dependent manner. Furthermore, we demonstrate that adipose-specific G-protein-coupled receptor (GPR)81 ablation, similarly to global GPR81 deficiency, ameliorates lactate-induced or tumour-induced adipose and muscle wasting in male mice, revealing adipose GPR81 as the major mediator of the catabolic effects of lactate. Mechanistically, lactate/GPR81-induced cachexia occurs independently of the well-established protein kinase A catabolic pathway, but it is mediated by a signalling cascade sequentially activating Gi-Gßγ-RhoA/ROCK1-p38. These findings highlight the therapeutic potential of targeting GPR81 for the treatment of this life-threatening complication of cancer.

Microplastic pollution in deep-sea sediments and organisms of the Western Pacific Ocean.

Microplastics are ubiquitous in marine environments. Sediments and marine organisms are recognized as the carriers and final destinations of microplastics. However, research on the concentration and abundance of microplastics in deep-sea sediments and organisms is limited. In this study, samples of sediments and organisms were collected from deep-sea locations of the western Pacific Ocean, with the depth ranging from 4601 m to 5732 m. Microplastics were extracted from the samples and analyzed by micro-Fourier-transform infrared spectroscopy. The average abundance of microplastics in the sediments was 240 items per kg dry weight of sediment. The microplastics were predominantly fibrous in shape (52.5%), blue in color (45.0%), and less than 1 mm in size (90.0%). The most commonly detected polymers were poly(propylene-ethylene) copolymer (40.0%) and polyethylene terephthalate (27.5%). The concentrations of polychlorinated biphenyls (PCBs), which are representatives of persistent organic pollutants, in the pore water of sediment samples were also investigated. A significant correlation between the distribution of microplastics and the PCB concentrations in sediments was found (P = 0.016). Microplastics were also detected in deep-sea organisms (i.e., Crinoidea, Pheronematidae, Ophiuroidea, and Gammaridea) in the sampling region, with an abundance of 0-3 items per individual biological sample. This assessment of microplastics in deep-sea sediments and benthic organisms of the western Pacific Ocean confirms that microplastic pollution exists in the deep-sea ecosystems of this region.