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Guo et al. show that Cdo1, a taurine-synthesis enzyme, interacts with PPARγ to promote its transactivation of genes encoding the lipases ATGL and HSL, thereby promoting adipose tissue lipolysis and ameliorating diet-induced obesity.
Qiao et al. reveal that a Ganoderma meroterpene derivative can prevent atherosclerosis by increasing the abundance of Parabacteroidesmerdae in the gut, which in turn will enhance branched-chain amino acid catabolism and lead to cardiometabolic benefits.
Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness.
A small-molecule aldolase inhibitor, aldolazin is reported and shown to selectively activate the lysosomal pool of AMPK, which has glucose-lowering effects in rodents.
Accumulation of β-amyloid plaques contributes to neuronal cell death in Alzheimer’s disease. In this study, Leng et al. describe a role for hexokinase 2 in metabolic reconfiguration in microglia that promotes phagocytosis and supports amyloid plaque clearance.
Hexokinase 1 is found to be secreted from hepatic stellate cells in large extracellular vesicles in response to TGF-β, and is subsequently taken up by hepatocellular carcinoma cells, where it promotes tumor progression and metastasis.
Kang et al. reveal that GAB, classically known as a neurotransmitter, can control pro-inflammatory TH17 cell and anti-inflammatory iTreg cell differentiation in a cell-autonomous manner, thus modulating T cell-mediated inflammation.
The tyrosine kinase receptor EphB4 is shown to interact with the insulin receptor to facilitate its endocytosis and degradation, thereby decreasing insulin signaling and promoting insulin resistance.
Achreja et al. develop a framework to identify collateral lethalities in cancer, uncovering MTHFD2 as a collateral lethal gene in UQCR11-deficient ovarian tumours.
Chen et al. show that the endoplasmic reticulum stress sensor IRE1α acts in white and beige adipocytes to restrain beige adipocyte activation, through regulation of lipolysis and Pgc1α messenger RNA levels, respectively.
Synergistic toxicity of alcohol and cannabinoid exposure in mice leads to impairments on motor coordination by affecting the activity of presynaptic cannabinoid type 1 receptors and extrasynaptic glycine receptors in cerebellar Purkinje cells.
Yang et al. show that neuronatin (NNAT) can explain part of the phenotypic variation of complex traits, independently of genetics or the environment. Such NNAT-dependent variations can stratify human cohorts into four metabolic sub-types, including two distinct types of obesity.
Alterations in hepatic lipid metabolism may contribute to the onset of non-alcoholic fatty liver disease as well as other metabolic disorders. In this work, Zhou et al. identify orosomucoid 2 (ORM2) as a regulator of lipid homeostasis in the liver.
RNA modifications have emerged as important regulators of RNA function. In this study, Peng, Chen, Wei and Guo et al. show that the 18S rRNA N6-methyladenosine methyltransferase complex METTL5–TRMT112 regulates hepatic lipid metabolism and contributes to hepatocellular carcinoma.
Baboota et al. investigate senescence as a driver of human NAFLD/NASH and show the roles of BMP4 and its antagonist Gremlin 1 as anti-senescent and pro-senescent molecules, respectively.
Alterations in cholesterol homeostasis may contribute to hepatic cancer aggressiveness. Liu, Tian, and Zhang et al. identify the long non-coding RNA SNHG6 as an important player in this process by linking cholesterol sensing with cancer cell growth through mTORC1 signaling.
A conjugate drug consisting of GLP-1 receptor agonist and the PPARɑ/ɣ dual-agonist tesaglitazar is shown to have superior anti-diabetic effects than monotherapy.
Zhang et al. use single-cell transcriptomics to map the cellular landscape of perinatal murine epididymal adipose tissue, and demonstrate that altering the adipogenic capacity of perinatal adipose progenitors has long-term effects on progenitor plasticity, tissue expandability and metabolic health in adulthood.
Amino acid-sensing is vital for adaptation to the nutritional environment. In this study, Kosakamoto et al. show that the non-essential amino acid tyrosine regulates the adaptive response to protein restriction via modulating ATF4 activity in Drosophila.
Extended exposure to breastfeeding in rodent pups protects them from diet-induced obesity in adulthood by increasing thermogenesis and energy expenditure. This is mediated by liver-derived FGF21 signalling to the lateral hypothalamic area.