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Hu et al. study the role of hexokinase 2 in microglial metabolism and function, and show its dual role under physiological and pathological conditions in a mouse model of stroke-induced neuroinflammation
Paterson and Yu et al. demonstrate that loss of the RNA alternative splicing factor RBFOX2 in the liver during a lipogenic diet leads to dysregulation of liver lipid and cholesterol homeostasis through a specific alternative splicing programme, which includes a splice switch of the high-density lipoprotein receptor gene Scarb1.
Liu et al. identify a non-metabolic mechanism through which lactate dehydrogenase A (LDHA) promotes cancer progression. This study shows that LDHA, independently of its enzymatic activity, directly interacts with and activates Rac1.
A mutation leading to ubiquitous ectopic expression of agouti signaling protein, which is not picked up in conventional genetic screenings, is reported in patients with severe childhood obesity.
Hosios et al. demonstrate that inhibition of mechanistic target of rapamycin complex 1 in cells and in tumors in mice leads to a lysosome-dependent but autophagy-independent shift in membrane lipid metabolism, resulting in increased intracellular triglyceride pools.
Zhong et al. show that increased lipid intestinal absorption can contribute to fat mass increase after dieting and this is mediated by Lactobacillus-secreted metabolites. Notably, Lactobacillus growth can be counteracted by refeeding a high-protein diet, thus preventing weight regain.
Hoang et al. show that mitochondrial RNA in young beige adipocytes triggers mitobiogenesis and thermogenesis, while an interferon response is avoided through vitamin D-mediated suppression of IRF7 expression.
Chronic pain is often accompanied by decreased appetite. The authors uncover the neuronal circuits that lead to reduced feeding in a mouse model of persistent pain, which involves cortical-to-hypothalamic glutamatergic signalling.
Ceasrine et al. show that a maternal high-fat diet leads to impaired serotonin bioavailability in the male fetal brain by disrupting the placenta–brain axis, which can cause long-lasting behavioural changes in the offspring.
In this study, Patrick et al. provide insight into the regulation of branched-chain amino acid metabolism and its impact on whole-body physiology by identifying and characterizing a metabolon formation.
Schneeberger et al. show that glutamatergic neurons within the dorsal raphe nucleus of the brainstem are enriched with the orexin 1 receptor Hcrtr1, which can be pharmacologically targeted to treat obesity in mice.
Bondareva and Rodríguez-Aguilera et al. use scRNA-seq to analyze transcriptomes of 375,000 endothelial cells from seven organs in male mice at various stages of obesity to identify organ-specific vulnerabilities.
Shi et al. show that neuregulin-4 derived from brown adipose tissue can reduce endothelial injury and inflammation and alleviate atherosclerosis in male mice, via Akt and nuclear factor-κB signaling
Diener and Dai et al. analyse blood metabolites from 1,569 individuals and identify metabolites associated with the microbiome, host genetics or under hybrid genetic–microbiome control.
Fenofibrate has been shown to inhibit SARS-CoV-2 replication in vitro. Results from a randomized clinical trial show that treating patients with COVID-19 with fenofibrate has no significant effect on clinically relevant outcomes.
Malita, Kubrak et al. show that the gut-derived hormone neuropeptide F suppresses sugar intake and increases the consumption of protein-rich food in Drosophila. This gives insight into the regulation of nutrient-specific appetite that ensures appropriate food choices to meet nutritional demands.
Using inducible transgenic mouse models, Joffin, Gliniak and colleagues demonstrate that altering mitochondrial iron levels in adipose tissue macrophages has profound effects on systemic metabolism in male mice.
In this study, Yu et al. engineer a decarboxylation cycle in the yeast cytoplasm that provides increased reductive power to enhance bioproduction of reduced chemicals.
Steuernagel and Lam et al. present HypoMap, an integrated reference atlas of the murine hypothalamus based on 384,925 hypothalamic cells from publicly available single-cell sequencing datasets.