Volume 3 Issue 8, August 2021

Diabetes therapeutic approaches continue to expand and to be refined. As the field moves toward more intensive insulin- and cell-based therapies, care must be taken to mimic healthy physiological insulin dynamics and avoid hyperinsulinemia, with its deleterious downstream complications.

Obesity is a growing public-health problem that has been linked to lifestyle changes affecting the diet, which in turn may lead to changes in the commensal microbiota. Hild et al. show that mice colonized with microbiota derived from wild-caught mice are protected against diet-induced obesity, specifically when this microbial colonization occurs early in life.

Considerable knowledge gaps remain regarding the mechanisms underlying how peripheral hormones affect the brain. Duquenne et al. previously found support for a possible route for leptin to enter the brain, but the results have been somewhat controversial. Now the authors provide further evidence and details in support of this route involving a tanycytic leptin shuttle.

Hild et al. find that a wild-derived microbiome protects against weight gain through early postnatal metabolic programming and brown adipose tissue activation.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

Duquenne et al. show that tanycyte leptin receptor expression is required for leptin to enter the brain and regulate peripheral lipogenesis and pancreatic β-cell function.

Cells with mitochondrial defects are shown to be eliminated by cell competition in the early mouse embryo, thus suggesting that cell competition acts as a purifying selection that optimizes mitochondrial performance during development.

Multi-omics characterization of ZIKA virus–infected mouse brains reveals metabolic reprogramming events, including dysregulation of NAD⁺ metabolism, the correction of which is shown to alleviate ZIKA virus–induced microcephaly.

Puurunen et al. demonstrate the safety and tolerability in patients with phenylketonuria of a genetically modified strain of E. coli encoding metabolic enzymes to metabolize phenylalanine to non-toxic metabolites.