Volume 6 Issue 10, October 2024

In this new instalment of our Career Pathways series, Marina García-Macia and Fei Yin highlight the impact and joys of building a team and share with us key milestones that have shaped their careers so far, including the importance of making the most of every situation, finding the right mentors, and pursuing the questions that they are passionate about.

A new approach to treating mitochondrial disorders is based on the transplantation of healthy mitochondria, and improves symptoms and survival in a mouse model of Leigh syndrome — a paediatric mitochondrial disease that is characterized by failure to thrive, lactic acidosis, and progressive degeneration.

A meta-analysis of genome-wide association study for eight traits related to pancreatic β-cell function, based on 26,000 individuals, identified 55 independent association signals mapping to 44 loci. This study highlighted new effectors of β-cell function.

In this issue of Nature Metabolism, nine people lacking growth differentiation factor 15 (GDF15) from conception are shown to be healthy, with normal development and fertility, providing some reassurance about the safety of blocking GDF15 in conditions like cachexia and pregnancy sickness, where GDF15 contributes to disease pathogenesis.

Carapeto et al. provide compelling evidence that exercise can have an inhibitory effect on cellular senescence in the pancreatic islets. Their results clearly demonstrate that serum collected postexercise can induce this effect in islets from either mice or humans.

In this issue of Nature Metabolism, Carrasco-Zanini et al. describe sets of modifiable and non-modifiable drivers of human plasma proteins. These findings may inform the design of precision prevention programs and highlight novel therapeutic targets.

This authoritative Perspective lays a foundation for the field of obesity research by comparing commonalities and differences between competing models of obesity pathogenesis and by defining terms that are at the core of this discussion.

Holst reflects on the development of GLP-1-based drugs for the therapy of obesity, from early observations to remarkable results in more recent clinical trials, discussing physiological, pharmacological and clinical considerations related to their use.

Administration of exogenous mitochondria from mice or humans, or stimulation of mitochondria transfer from haematopoietic cells through bone marrow transplant from wild-type mice, is shown to improve morbidity and mortality in a mouse model of the mitochondrial disease Leigh syndrome.

In a genome-wide association study for traits related to pancreatic beta-cell function in 26,000 individuals, 55 independent associations mapping to 44 genetic loci are identified.

This study reports and characterizes the impact of loss-of-function GDF15 variants in human individuals.

LXRα is highly expressed in hepatocytes, where it regulates cholesterol abundance and stimulates lipogenesis. The authors provide evidence in humans and mice that impaired LXRα signalling is hepatotoxic, despite its potent lipogenic actions.

Genetic and pharmacological inhibition of the overproduction of oxalate in the liver alleviates metabolic dysfunction-associated steatohepatitis in male mice.

Grankvist et al. combine global isotopic tracing and metabolic flux modelling to characterize metabolic networks in human intact liver tissue.

Exercise training decreases pancreatic islet senescence through glucagon and AMPK signalling in mouse and human islets, which could have implications for T2DM therapeutics.

Oral administration of the anti-diabetic drug acarbose is shown to enhance the efficacy of cancer anti-PD-1 immunotherapy in female mice by modulating the composition and metabolism of the gut microbiota.

The authors systematically study biological influences on the human plasma proteome in a large cohort, thereby revealing causal associations between plasma proteins and modifiable risk factors for protein–disease associations.