Volume 3 Issue 9, September 2021

How to adjust metabolic rate (MR) in mice that differ in body mass and composition continues to lead to controversies. Here, the challenges that reside in the analysis of mouse MR are highlighted to spur consensus on the unequivocal use of regression-based analysis to maximize reliability and relevance of conclusions.

Exosomes mediate endocrine crosstalk between distant organs and contribute to disease development. Here, Ji, Luo et al. report that hepatocyte-derived exosomes exert temporally divergent roles in glucose regulation. Exosomal roles strongly differ between early and chronic obesity and this shift in function likely reflects altered exosomal miRNA cargos.

When the ability of lymphatic vessels to transport fluid and macromolecules is perturbed, local adipose tissue often expands. Cao et al. identify destabilized, leaky mesenteric lymphatic vessels in obesity and demonstrate that correcting this dysfunction with a lymphatic-targeting drug improves systemic glucose metabolism.

Over-nutrition is a major driver of obesity, but the mechanisms that promote and perpetuate it remain poorly understood. A recent study explores a role for umami taste in driving leptin resistance, hyperphagia and hypothalamic inflammation via overproduction of uric acid.

When is a calorie not just a calorie? In the current issue of Nature Metabolism, Roy et al. use recombinant inbred strains of mice to investigate the role of genetic background in the response to dietary fat. Notably, both lifespan and weight gain have been found to be highly dependent on genotype, thus highlighting the need for a personalized approach to dietary interventions.

Clearance of dMiro from the outer mitochondrial membrane is a prerequisite for mitophagy of dysfunctional mitochondria. Li et al. find that oxidative stress stabilizes dMiro via its interaction with dMIC60. Dissociating this complex by genetic or pharmacologic interventions counteracts neurological aging in flies.

The maternal diet can impact offspring development, yet the mechanisms responsible for this remain largely unknown. New research shows that oocyte metabolites, specifically NAD⁺ and the methyl donor S-adenosylmethionine, can mediate the impact of maternal nutrient stress on the progeny through metabolic reprogramming in Drosophila.

Bidault et al. find that interleukin-4 activates SREBP1 to promote de novo lipogenesis that consumes NADPH to drive alternative activation of macrophages through the accumulation of reactive oxygen species.

Ji and Luo et al. show that miR-3075 in hepatocyte-derived exosomes from mice at early stages of obesity improves insulin sensitivity in chronically obese mice, while hepatocyte exosomes from chronically obese mice induce insulin resistance.

Cao et al. find that the mesenteric lymphatic system becomes dysfunctional during obesity in mice and humans, leading to visceral adipose tissue accumulation and insulin resistance.

Found in umami foods and known for their savoury taste, monosodium glutamate and inosine monophosphate are shown to induce metabolic syndrome in mice through induction of purine degradation in the liver and brain and through the formation of uric acid.

A combination of single-cell approaches, lineage tracing and metabolomics is used to characterize the changes to intestinal stem cell function in the small intestine that underlie intestinal maladaptation in mice fed an obesogenic diet.

Roy et al. quantify the impact of a high-fat diet across genetically diverse strains of mice, revealing a generally negative effect on lifespan but also a wide variability.

Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.

Redox signal transduction from the mitochondrial matrix to the cytosol is shown to be mediated through interaction between MIC60 and Miro, the disruption of which ameliorates oxidative stress in Drosophila.

Hocaoglu et al. find a conserved shift in redox metabolites in fly oocytes and mammalian cells in response to mitochondrial respiratory quiescence that leads to reprogramming of progeny metabolism.