Search

Olfactory perception of food-derived odors influences feeding behavior, but the underlying neural pathways remain unclear. Here, the authors show that prolonged exposure to food odor suppresses food intake and body weight gain by activating an olfactory bulb–hypothalamus circuit.

Imidazole propionate produced by gut microbiota is associated with atherosclerosis in mouse models and in humans, and causes the development of atherosclerosis through activation of the imidazoline-1 receptor in myeloid cells.

The authors identify a neural population in the basal forebrain of mice that is key for maintaining energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.

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.

Neuropeptide Y signalling in the periphery contributes to the regulation of metabolic and energy homeostasis. Here the authors show that blocking Y1R signalling in peripheral tissues using the selective antagonist BIBO3304 ameliorates diet-induced obesity and improves whole-body glucose metabolism.

The mechanistic involvement of sonic hedgehog signaling in nonalcoholic steatohepatitis is not clear. Here, the authors show that sonic hedgehog protein regulates the stability of HSP90β, enabling hepatocytes to secrete exosomes containing miR-28-5-p to promote NASH development.

This study reveals neuronal targets of Lac-Phe in the hypothalamus that mediate its suppression of food intake.

Here, the authors demonstrate increased global lactylation levels and in the joints of rheumatoid arthritis patients. NFATc2 is identified as a key target gene regulated by histone H3 lysine 9 lactylation that exacerbates disease progression by enhancing the cartilage invasive function of fibroblast-like synoviocytes.

White adipose tissue (WAT) dysfunction leads to ageing-related metabolic disorders. Here, the authors show that the FMO3-TMAO axis in adipocytes induces senescence and inflammation in WAT microenvironment via NLRP3 inflammasome, leading to systemic glucose, lipid, and energy dysregulation in ageing

In mice, prolonged consumption of a high-fat diet decreases interest in calorie-rich foods as a result of reduced neurotensin expression and signalling, which uncouples hedonic feeding behaviour linked to neurons projecting from lateral nucleus accumbens to ventral tegmental area.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Increasing mitochondrial oxidative capacity and energy expenditure holds therapeutic potential for obesity and metabolic disorders. Here, the authors identify MTCH2 as a mitochondrial regulator of fatty acid oxidation via interaction with CPT1.

Studies in mice show that acute stress activates hyperglycaemia via activation of a medial amygdala–ventral hypothalamic circuit that controls glucose metabolic responses in the liver, independently of adrenal and pancreatic hormones.

Obesity-associated AT fibro-inflammation and metabolic disturbances are linked to PEPD activity and PEPD extracellular levels.

Excess caloric intake leads to increased thermogenesis in brown adipose tissue, to limit weight gain. Here, the authors show that neuropeptide FF receptor-2 signalling promotes thermogenesis via control of NPY expression in the arcuate nucleus, and that it absence in mice leads to a failure of activation of diet-induced thermogenesis and the development of exacerbated obesity.

The authors previously developed a mouse model of parenteral nutrition-associated cholestasis (PNAC) that is dependent on parenteral phytosterols and intestinal injury with DSS. Here they refine the model and show that PNAC pathology is dependent on recruitment of hepatic macrophages and IL-1 signaling.

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

Engineered kill-switch-encoding Mycobacterium tuberculosis infects, elicits immune responses and is cleared from immunocompetent and immunocompromised mice, providing a model of controlled tuberculosis infection.

Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

Two polypeptides synthesized by common bacterial strains in human gut microbiota lower body fat and blood glucose and increase bone density, improving the metabolism of rodents.

AgRP neurons of the arcuate nucleus of the hypothalamus promote homeostatic feeding yet are rapidly suppressed by food-related sensory cues. The authors identify a population of inhibitory DMH-LepR neurons that relays real-time information about the nature and availability of food to dynamically modulate ARC-AgRP neuron activity and feeding behavior.

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.

Using a zebrafish-based screen, Civiletto and colleagues identify the herb-derived metabolites thymol and carvacrol as activators of autophagy and mitophagy, demonstrating their therapeutic potential in C. elegans and mouse models.

Schneeberger et al. show that glutamatergic neurons within the dorsal raphe nucleus of the brainstem are enriched with the orexin 1 receptor Hcrtr1, which can be pharmacologically targeted to treat obesity in mice.

Mitochondrial dysfunction contributes to septic cardiomyopathy and poor outcomes. Here, the authors identify a cardiomyocyte-enriched non-coding RNA that preserves mitochondrial function and reduces mortality in septic mice by preventing citrate synthase acetylation.

In addition to promoting overconsumption, palatable diets dampen daily intake patterns, which further augments metabolic dysfunction. Here, the authors find that in mice, circadian clocks in dopaminergic neurons in the ventral tegmental area drive hedonic appetite rhythms.

Using metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma mouse models, an ATP citrate lyase inhibitor reduces tumour burden and enhances efficacy of current standards of care.

Whether amino acids act on cellular insulin signaling remains unclear. Here, the authors find that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake and positively correlated with T2D onset.

Melanocortin action is known to regulate body weight. Here the authors report that while inhibition of the hypothalamic melanocortin action leads to obesity in mice, chronic activation of melanocortin action is not sufficient to cause weight loss.

IPF arises from the maladaptive differentiation of lung stem cells into bronchial epithelial cells rather than AT1 cells. Here, Warren, R et al. report that stem cells with the highest Myc levels become supercompetitors that drive remodeling.

The ability to encode and recall information about food is critical for survival. We reveal that ventral hippocampus projections to the lateral hypothalamus encode meal-related memories, and that disruption of this circuit promotes excessive eating.

Endocannabinoid signalling processes are implicated in body weight regulation. Here, authors used viral-genetic tools to identify the enzyme ABHD6 in postsynaptic mesoaccumbal neurons is a key determinant of body weight and reward-relevant behaviour.

The failure of metabolic tissues to respond to insulin is an early marker of type 2 diabetes. Here, the authors show, using global phosphoproteomics, that insulin resistance is caused by a marked rewiring of both canonical and non-canonical insulin signalling, and includes dysregulated GSK3 activity.

A combination of animal studies, data from a clinical trial and insights from an observational cohort suggest that, in individuals with metabolic dysfunction-associated steatohepatitis, semaglutide improves liver histology by reverting patient proteomes to better mimic the proteome of individuals without the disease.

Ventral striatal dopamine D3 and D1 receptors regulate motivation and reinforcement, respectively, through dissociable physiological actions.

Insulin and insulin-like growth factor 1 signalling pathways have overlapping effects on adipose tissue and glucose homeostasis. Boucheret al.created fat-specific double knockouts of these pathways and demonstrated their crucial role for adipocyte development, metabolism and thermogenesis in mice.

TFE3-fusions are known to drive both epithelial and mesenchymal renal tumors. Here, the authors generate a transgenic mouse model of renal tumorigenesis expressing the human SFPQ-TFE3 fusion, showing that the fusion regulates mTORC1 activity and induces lineage plasticity.

Boccella, Yu and colleagues reveal that the transmembrane protein ANTXR1 regulates post-infarction fibrotic remodeling, and its inhibition blocks collagen turnover and improves heart function.

Grb10, an adaptor protein known to regulate insulin signalling, can interact with the leptin receptor for enhancement of leptin signalling in hypothalamic AgRP and POMC neurons in mice.

This study presents FolTAC-dual, a folate receptor-mediated platform for dual degradation of EGFR/HER2 and PD-L1/VISTA, offering a strategy to overcome drug resistance and enhance antitumor immunity for cancer treatment.

The mechanisms underlying the regulation of the skin thermal barrier are poorly understood. Here the authors show that the thermal properties of the skin are reactive to diet and that skin is a target for dietary fat delivery.

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.

Glycolysis-derived lactate was identified as substrate for histone lactylation which has been reported to play a significant role in transcriptional regulation. However, it’s role in the hypothalamus is still unknown. Here, the authors show the importance of Fam172a and lactate in the development of obesity and related metabolic disorders

Enrichment for efferocytic macrophages in the islets of Langerhans promotes the accumulation of anergic-like CD4⁺ T cells and dampens autoimmune diabetes.

Dietary cysteine enhances intestinal stem cell-mediated intestinal repair following injury by promoting CD8 T cell-regenerative immune responses.