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Brown adipose tissue has a crucial role in regulating body temperature in mammals. Recent research delves into the notion of thermogenic memory and identifies a subset of adipocytes that enhance the response to repeated stimulation events via de novo lipogenesis.
Lundgren et al. show that in response to transient cold exposure, a distinct subpopulation of brown adipocytes carries out a lipogenic response involving production of acylcarnitines, which enables an improved thermogenic response to secondary cold exposure.
This study presents a comprehensive pipeline to profile transmembrane receptors involved in macrophage-driven inflammation in pancreatic islets during the onset of diabetes. The authors identify GPR132 as a mediator of macrophage-driven inflammation and find compounds that reduce inflammation and improve glycaemic control.
The authors develop synthetic biotics, engineered from bacteria, that could treat phenylketonuria, an inherited defect of phenylalanine (Phe) metabolism.
Here we reflect on touching points between basic science and clinical research, while highlighting key points to consider when submitting clinical work to our journal.
As most studies on the action of insulin in the brain have focused on men, metabolic changes during the menstrual cycle in women remain poorly understood. Using intranasal insulin administration during hyperinsulinaemic–euglycaemic clamps and functional MRI, Hummel et al. show reduced insulin sensitivity during the luteal phase.
Yao and Gong et al. identify WD40 repeat-containing protein 6 (WDR6) to be upregulated in the liver of insulin-resistant mice. WDR6 contributes to promoting hepatic de novo lipogenesis during insulin resistance by upregulation of fatty acid synthase, and the authors identify a small molecule to inhibit this effect of WDR6 and reduce hepatic steatosis.
In young women, brain insulin action enhances peripheral insulin sensitivity, but only during the follicular phase of the menstrual cycle. This effect is absent in the luteal phase, possibly due to hypothalamic insulin resistance.
The molecular underpinnings of the extensive cellular, morphological and functional plasticity of skeletal muscle in exercise training are poorly understood. We have now begun to unravel the complex epigenetic, transcriptional and proteomic networks that determine the muscle response to exercise in a manner depending on the training state.
Glucagon-like peptide 1 (GLP-1) controls insulin secretion and body weight through activation of its receptor, GLP1R. Large-scale functional analysis of 60 GLP1R genetic variants revealed that loss-of-function (LoF) phenotypes, in particular of cell surface expression, are associated with impaired glucose control and increased adiposity.
Gao et al. perform functional profiling of 60 genetic variants of glucagon-like peptide 1 receptor (GLP1R) in vitro, and link variants with impaired GLP1R cell surface expression or cAMP activation to defective insulin secretion in vitro and to impaired glucose homeostasis and adiposity in the UK Biobank.
Mishra and Townsend present an overview of the regulation, function and plasticity of adipose tissue sensory nerves that are relevant for metabolic processes in health and disease.
A mouse pancreatic islet atlas comprising over 300,000 single-cell transcriptomes was integrated from nine biologically diverse datasets to unify existing knowledge in the islet biology community. This interactively accessible resource reveals new insights into the molecular identity and plasticity of islet and β-cells across sex, life span and diabetes progression.
The authors explore the molecular signature of skeletal muscle adaptations to an acute bout of exercise in mice, providing a valuable resource that includes transcriptomic, epigenetic, proteomic and phosphoproteomic changes in muscle plasticity.
Longitudinal deep lipidome profiling reveals >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation.
This study reports the mouse islet atlas, a curated resource integrating scRNA-seq data of over 300,000 cells from nine datasets, covering pancreas development, homeostasis and disease states.
Subcellular quantitative analysis has been a long-standing goal of mass spectrometry imaging, but was originally thought to be unattainable. However, recent advances have made organelle-level absolute quantification through mass spectrometry imaging a reality, thanks to the development of nano secondary ion mass spectrometry.