Nature Metabolism

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Rare damaging GLP1R variants in 13,725 GLP-1RA–treated adults are linked to less weight loss with semaglutide, while tirzepatide weight loss remains near-normal in carriers.

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Redirecting intestinal cholesterol metabolism via gut microbiota generates 4-cholesten-3-one (4-C-3), which suppresses colorectal cancer growth and enables regression in preclinical models.

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Endotrophin (ETP), the C-terminal cleavage fragment of collagen VI α3, is linked to disease progression, with elevated levels tied to fibroinflammation and tissue remodeling across organ systems.

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GUSB-enriched sympathetic neurons in male mice secrete GUSB after cold exposure, driving extracellular matrix remodeling that is essential for thermogenic programming, including CS fragment generation.

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Lactate-dependent lactylation of PGK1 at K131 activates Aurora B via T232 phosphorylation, promoting mitotic progression in cancer cells.

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Whole-blood NAD levels in 1,068 adults do not decline with age in healthy individuals, but are reduced in cardiovascular disease and hypertension.

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Cells dynamically balance salvage and de novo nucleotide synthesis across physiological states, with pathway choice shaped by precursor supply, demand, and regulatory programs rather than fixed enzyme presence.

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Low pyruvate carboxylase expression creates asparagine dependency in respiration-compromised cells with high mtDNA heteroplasmy, with translational defects above 70% that asparagine or PC can reverse.

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A futile Na+/K+ transport cycle, driven by ATP1A2, is preferentially amplified in mouse and human beige adipocytes and boosts UCP1-independent energy expenditure.

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NNMT overexpression in mouse granulosa cells reduces H3K27me3 and increases RARB expression, amplifying ovarian androgen synthesis and sustaining hyperandrogenism in PMOS models.

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Dynamic, bidirectional crosstalk between metabolic organs and endocrine mediators is proposed as a central determinant of female reproductive function across the life course.

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Cyclic interferon signaling in tanycytes drives oestrous-cycle–linked Irf7 and Cxcl10 expression in female mice, producing temporally patterned leukocyte and cytokine responses.

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In primary human fibroblasts, mitochondrial respiratory chain inhibition creates NADH-reductive stress alongside profound NADPH depletion, and NADH/NAD+ normalization alone does not rescue proliferation arrest.

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L-arginine directly binds the Asp31 site of NLRP3 and inhibits inflammasome assembly, blocking ASC interaction and activation in macrophages and mouse disease models.

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Acute exercise in 25 healthy men regulates over 3,000 proteins across plasma, saliva, and urine with distinct, fluid-specific temporal dynamics.

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In 15 participants with metabolic dysfunction-associated steatotic liver disease, 6-week PF-06835919 ketohexokinase inhibition improves hepatic insulin sensitivity and lowers intrahepatic lipid and saturated fatty acid content.

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In 57 healthy-weight adults, nutritionally matched ultraprocessed food meals produce greater insulinaemic and energetic responses and lower peak carbohydrate oxidation than non-UPF meals.