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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.
A single transfer of blood from old male mice is shown to induce cellular and tissue senescence in young animals, unless old mice are treated with senolytic drugs before blood exchange.
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.
The key regulator of lysosomal biogenesis, Tfeb, is shown to directly induce Irg1 transcription and mitochondrial itaconate production to restrain bacterial growth in macrophages.
Gao et al. devise a global metabolic rewiring approach to overcome methanol toxicity and use it as sole substrate for enhanced free fatty acid production in yeast, which may then be beneficial for global carbon neutrality.
Ultraviolet exposure on the skin promotes food intake and body weight gain in males, but not females, by increasing ghrelin expression in skin adipocytes.
Park et al. shed light on the dynamics of DNA demethylation during adipocyte differentiation, which is shown to be regulated by the transcription factor C/EBPδ and the DNA methylation eraser TET3.
Anti-PD-1 immunotherapy often leads to undesired side effects such as colitis. In this study, Wu, Hu, Han et al. report a metabolic reconfiguration in colonic lymphoid tissue inducer (LTi) cells regulated by PD-1 signaling that modulates inflammatory states in the gut.
Hypothalamic AgRP neurons are shown to control peripheral and central levels of lysophospholipids in association with food deprivation, which leads to cortical excitability, hyperphagia and body weight gain.
Targeting extracellular matrix (ECM) remodelling is a feasible avenue to prevent cancer aggressiveness and metastasis. In this study, Kay et al. show that metabolic flux in cancer-associated fibroblasts is coupled to enhanced proline synthesis by PYCR1 to support elevated production of collagen-rich ECM, thus contributing to cancer spreading.
Sugimoto et al. show that maresin 2, a specialized pro-resolving mediator that is secreted from brown adipose tissue upon cold exposure, contributes to amelioration of obesity-induced inflammation.
Li et al. show how mitochondrial content is regulated when oxygen is depleted, as well as how this process is impaired in cancer types related to the von Hippel–Lindau syndrome.
Hu and Zhao et al. identify a mechanism mediated by CCL18 and RFX5, through which tissue macrophages adapt their metabolic programme to nutrient stress in the context of autoimmune diseases.
Production of oxidized biomass is necessary to support cancer cell proliferation. In this work, Li et al. provide a quantitative analysis of the cellular needs and biochemical bottlenecks in lipid biosynthesis arising from the requirement to regenerate the cofactor NAD+.
In this work, using a combination of metabolomics and CRISPR-based genetic screens, Garcia-Bermudez, Badgley, Prasad et al. show that pancreatic cancer cells overcome aspartate limitation in hypoxia by upregulating macropinocytosis.
Itaconate is an immunomodulatory macrophage metabolite. Mesaconate, a structurally similar molecule, is shown to be synthesized from itaconate in inflammatory macrophages and shows similar immunomodulatory effects, despite not repressing tricarboxylic acid cycle activity nor inhibiting succinate dehydrogenase activity.