Physiology articles from across Nature Portfolio

Metabolomic analysis of plasma from metformin-treated humans, together with mechanistic studies in mouse models, reveals that metformin selectively inhibits mitochondrial complex I in the intestinal epithelium. This mechanism unifies multiple clinical effects of metformin, including enhanced intestinal glucose use, improved postprandial glycaemic control and increased production of GDF15 and N-lactoyl-phenylalanine.

Not all metabolic and bariatric surgical operations are equally effective. Novel triple-blinded randomized clinical trial data suggest that procedures differentially reshape the gut microbiome, which may drive clinical differences in weight loss and metabolic improvement.

Cell metabolism is a dynamic network of highly interconnected biochemical reactions. In this issue of Nature Metabolism, time-lapse analysis of the amino acid aspartate revealed an unexpected regulation of de novo pyrimidine biosynthesis by the tricarboxylic acid cycle metabolite succinate, with implications for the cell cycle and DNA damage response.

RASSF4 associates with PKD2 to enhance its channel function and suppress RAS/MAPK signaling, mitigating polycystic kidney disease phenotypes and highlighting a potential therapeutic target for ADPKD.

Apolipoprotein E (APOE) is the strongest genetic influence in Alzheimer’s disease (AD). Compared to the most frequent allele, ε3, the ε4 allele increases AD risk, and the ε2 allele is protective. Here, in a multicohort proteomic study, the authors show that APOE ε2 and ε4 are linked to distinct early protein signatures before amyloid pathology, helping explain why they have opposite effects on AD risk.

There are a multitude of red-light emitting consumer goods, but do they really do anything for your health? We look at the science behind the hype — plus, the increasing levels of obesity in lower-income countries.

Findings reveal that stem-like CD8⁺ T cells migrate from renal lymph nodes and cause tissue damage in lupus nephritis.