Search

Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.

A study reveals a gut–brain sensory pathway through which the microbial component flagellin activates neuropod cells in the colon to signal the brain and reduce feeding in mice.

Microglia and border-associated macrophages play a role in regulating cerebral blood flow (CBF), but the underlying mechanisms are unclear. Here, the authors show a role for microglial CD39 in the regulation of basal CBF and neurovascular coupling.

The genetic determinants of sex-specific differences in obesity are still incompletely understood. Here, the authors demonstrate that adipocyte specific loss of Trim28 in committed adipocytes leads to sex specific differences in the development of obesity, and that this phenotype is associated with altered metabolic flexibility and lipid metabolism.

The roles of distinct dopaminergic neuron subpopulations and the circuit projections driving their activity during threat behaviors remain incompletely understood. Here, the authors demonstrate that substantia nigra pars lateralis dopamine neurons receive selective, robust excitation from auditory and temporal association cortices, which, combined with rapid action potential firing, contributes to auditory threat conditioning.

The ketogenic diet is a low-carbohydrate, high-fat diet that forces a metabolic switch towards fatty acid oxidation. Here, Goldberg et al. show that a ketogenic diet initially improves metabolic health and expands adipose tissue γδ T cells that are important for glycaemic control during obesity.

Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

Food intake is determined by learned appetitive responses and physiological “appetition” signals after eating begins. Here, authors show melanin-concentrating hormone (MCH)-producing neurons integrate these processes to promote caloric intake.

Gonzalez-Hurtado, Leveau and colleagues characterize adipose resident tissue macrophages across lifespan in mice, finding that nerve-associated macrophages, which mitigate inflammation and control lipolysis and catecholamine resistance, are lost during aging.

Feeding-relevant vagal signaling occurs between the gastrointestinal tract and the brain, but it is unclear if this pathway influences cognitive processes. This study shows that endogenous gastrointestinal derived vagal sensory signaling promotes hippocampal-dependent memory function via a multi-order brainstem–septal pathway.

Obesity represents a risk factor for cancer and compromises immune function, however the mechanisms linking the two together are not fully known. Here authors show in a mouse sarcoma model that obesity increases tumour incidence, impairs intra-tumoral T cell immunity but paradoxically increases sensitivity to immune therapy via impairing immunoediting.

The chimeric cytokine IC7Fc combines the beneficial effects of the cytokines IL-6 and CNTF on weight loss and metabolism in mice, with no obvious side effects in mice and non-human primates.

Glucagon plays a key role in regulating blood glucose levels. Here, Liu et al. show that

activation of α-cell Gs signaling promotes the release of glucagon from pancreatic islets and ensures the synthesis of sufficient amounts of glucagon.

Although the use of thiazolidinediones in the treatment of type 2 diabetes is controversial, they still comprise an important class of insulin-sensitizing drugs. In two reports, new evidence emerges that these drugs rely on the activation of their target, PPAR-A, in the brain to improve hepatic insulin sensitivity and increase food intake and reduce energy expenditure.

Sandhoff disease (SD) is a lysosomal storage disorder caused by deficiency in the β subunit of the β-hexosaminidase enzyme. Here, the authors show via bone marrow-based microglial replacement in a SD mouse model that myeloid-derived β-hexosaminidase is necessary for maintaining neuronal health.

Combining rabies-based connectomics with single-nucleus transcriptomics, the authors identify a neural circuit through which GLP-1 receptor agonists suppress appetite in mice.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

Brain region-specific oligodendrocyte population dynamics are unclear. Here the authors implement long-term in vivo three-photon imaging to determine those dynamics in the cortical and subcortical areas in the living intact and demyelinated adult mouse brain.

A modular anti-albumin nanobody conjugated to a STING agonist enhances antitumour immunity by improving pharmacokinetics, tumour accumulation and immune responses, inhibiting murine tumour growth and enhancing cancer immunotherapies.

Impulsive behaviour is common in various neuropsychiatric disorders. Here, the authors identify a pathway from the lateral hypothalamus to the ventral hippocampus and the role of melanin-concentrating hormone signaling in these neurons in specifically regulating impulsivity.

In this double-blind, randomised, crossover trial, a diet rich in fermentable foods was shown to improve the glucose-lowering efficacy of metformin due, at least in part, to changes in gut microbiota composition.

Xiao and Kennelly et al. show that Aster-mediated nonvesicular cholesterol transport in the liver regulates hepatic and systemic lipid homeostasis during fasting, as well as reverse cholesterol transport.

Amino acids availability is normally a limitation for protein synthesis and can determine cancer progression and therapy response. Here, the authors show that MYC-associated cancer has a dependency on tryptophan not because of translation regulation, but Indole 3-Pyruvate synthesis.

In mouse studies, metformin treatment results in increased secretion of growth/differentiation factor 15 (GDF15), which prevents weight gain in response to high-fat diet, and GDF15-independent lowering of circulating blood glucose.

Group 2 innate lymphoid cells (ILC2s) are immune cells present in adipose tissue that contribute to metabolic homeostasis. Here the authors show that Death Receptor 3 (DR3) engagement on ILC2s ameliorates glucose tolerance, protects against insulin-resistance onset and reverses established insulin-resistance.

Statins are lipid-lowering drugs that prevent cardiovascular disease but tolerability is limited by severe side effects in muscles. Here the authors elucidate a liver-specific activation mechanism for bempedoic acid, a novel cholesterol-lowering drug, and show how it effectively reduces LDL-C and atherosclerotic burden in mice, but does not cause myotoxicty.

Immune cells are important regulators of adipose tissue function, including adaptive thermogenesis. Here the authors show that mice with Krüppel-like factor 3 (KLF3) deficiency in bone marrow-derived cells have increased adipose tissue beiging which may at least in part be due to altered eosinophil paracrine signaling.

Bond et al. show that inducible PolG mutation in muscle causes mtDNA damage and muscle wasting. This is driven by the integrated stress response (ISR) and reduction in folate intermediates, linking impaired folate metabolism with ISR/disease induction.

The authors test the model that microglia are crucial for the developmental refinement of neural circuitry by depleting them with PLX5622. Microglia prove dispensable for the experience-dependent maturation of visual circuitry during development.

Type-2 innate lymphoid cells (ILC2s) are an immune population secreting Th2 cytokines playing a role in the regulation of adipose metabolic homeostasis. Here the authors show that engagement of GITR, a member of the TNF superfamily, in activated ILC2s is protective against insulin resistance in both a preventive and a therapeutic manner in the context of obesity.

The aspartate aminotransaminase GOT1 is important for maintaining redox balance. Here, the authors show that inhibition of GOT1 in pancreatic cancer cells leads to cell death via ferroptosis.

Germ-free mice were colonized with complex defined communities to show T cell recognition of commensals is focused on widely conserved, highly expressed cell-surface antigens, opening the door to new therapeutic strategies.

The anti-diabetic drug metformin is shown to elevate plasma levels of the hormone GDF15. This increase in GDF15 is required for reductions in appetite and body mass, which are known to contribute to the beneficial metabolic effects of the drug.

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using laboratory mice to study stem cell ageing.

Costa-Verdera et. al describe a mechanism by which AAV vector genomes activate P53-mediated signalling in CNS cells involving downstream STING activation and pro-inflammatory responses. Inhibition of either P53 or STING prevented target-cell apoptosis and inflammatory signalling.

Robbins and colleagues show that cigarette smoke-induced endothelial dysfunction enables atherosclerotic plaque macrophages to drive abdominal aortic aneurysm formation in a mouse model of atherosclerosis.

The multidomain scaffold protein SH3 and multiple ankyrin repeat domain 3 (SHANK3) can bind GTP-bound Ras and Rap small GTPases. Here the authors show that, by binding active KRAS, SHANK3 maintains oncogenic KRAS/MAPK/ERK signaling at an optimal level while its depletion in KRAS-mutant cancer cell lines results in ERK signalling overdose and impaired cell proliferation.

Ammonium is detected by chemosensory systems of humans and other animals to guide avoidance or attractive behavior. Here, the authors show that the proton channel OTOP1 is activated by ammonium, is required for ammonium taste responses in mice, and identify a conserved residue involved in ammonium sensitivity.

Fentanyl continues to drive the opioid crisis by contributing to >70,000 deaths per year in the US. Here, the authors investigate a candidate medication for fentanyl overdose prevention (monoclonal antibody CSX-1004) demonstrating its mitigation of fentanyl’s effects in preclinical animal models.

Transcriptomic and proteomic analyses show that high levels of the extracellular-matrix protein osteopontin are associated with the attenuated foreign-body response elicited by breast silicone implants wrapped with acellular dermal matrix.

InducTn-seq, a method for inducible mutagenesis followed by transposon insertion site sequencing, enables temporal control of transposition to bypass population bottlenecks and enable the quantification of gene fitness during in vivo Citrobacter rodentium infection.