Metabolism articles within Nature Communications

Glucocorticoids are known to induce insulin resistance via transcriptional activation of genes related to liver gluconeogenesis and insulin resistance. Here the authors report that in male mice treated with glucocorticoids, the transcriptional co-regulator EHMT2 is involved in the induction of Irs2 (a gene promoting insulin action) to restrict the extent of insulin resistance in the liver.

Isotopologue spectral analysis was originally designed to assess metabolic fluxes from bulk samples. Here, the authors adapted this approach to infer fluxes from discrete regions in tissue by using mass spectrometry imaging, showing increased fatty acid synthesis flux in brain tumors of mice.

Although it is known that cellular crosstalk between endothelial cells and brown adipocytes is essential, it remains poorly understood. Here the authors show that SCF derived from the surrounding endothelial cells promotes lipid accumulation in BAT by enhancing lipogenic enzymes in through c-Kit activation.

Beige adipocytes quickly transition into white adipocytes upon the removal of stimuli, limiting their therapeutic potential for chronic metabolic diseases. In this study, the authors show that inhibiting Cdkn2a-Becn1 mediated autophagy can maintain beige adipocytes and provide long term metabolic health benefits in mice.

How human brain activity relates to peripheral metabolism is not known. Here, the authors find that intracranial activity is strongly coupled to peripheral glucose variations across multiple brain regions and is sufficient for decoding of glucose levels.

We know that nutrition and obesity can impact male fertility, but specific dietary guidelines for men trying to conceive don’t exist. Here the authors show that diet composition is likely more important than body fat in influencing reproductive traits and each macronutrient has different impacts.

There is an urgent need for biomarkers for type 2 diabetes progression that provide a deeper understanding of the disease process. Here, the authors identify biomarkers in three molecular classes, replicate them in other cohorts and explore top protein biomarkers in detail in functional studies.

Adipose tissue thermogenesis plays a role in appropriate response to cold exposure through incompletely understood mechanisms. Here the authors report that acute cold exposure increases the serum levels of bradykinin, which induces brown adipose tissue thermogenesis and white adipose tissue browning in male mice.

Mitochondria modulate both normal and premature aging, yet if primary oxidative phosphorylation deficiency can cause progeria has been unclear. Here, the authors show that mice with severe isolated respiratory complex III deficiency display cellular senescence and juvenile-onset segmental progeria.

Obesity and a high-fat diet can lead to insulin resistance in a process involving macrophage-mediated inflammation of adipose tissue. Here the authors show that glucocorticoid receptor-deficient macrophages have an elevated inflammatory response which aggravates insulin resistance implicating that glucocorticoids promote insulin-sensitizing actions via adipose tissue macrophages during obesity.

The loss of nicotinamide adenine dinucleotide is reported to be associated with muscle mitochondrial dysfunction in murine cancer models. Here the authors show that niacin supplementation improves mitochondrial metabolism and reduces muscle wasting in mouse models of cachexia.

The timing of NAD + supply determines its efficacy to treat metabolic disease. Here, the authors show that increasing NAD + at the early active phase maximizes weight loss and glucose regulation in mice. NAD + can displace the phase of the liver clock which can cause circadian misalignment.

Many transcriptomic pathways in the liver show circadian rhythms, which have been reported to be disrupted in aged mice. Here the authors report that the expression of transcription factor Egr-1 decreases and its rhythm is shifted with age in the liver of male mice, and that deletion of Egr-1 results in increased liver fat accumulation.

Activation of white adipose tissue (WAT) thermogenesis alleviates obesity-associated metabolic disorders in rodents. Here the authors report that the m6 A RNA modification reader YTHDF1 promotes WAT thermogenesis in a study with male mice, and may be a potential target for the treatment of obesity.

Inhibition of AMPK leads to metabolic perturbations yet how AMPK is inactivated is not fully understood. Here the authors show protein phosphatase 6 subunit SAPS3 is a negative regulator of AMPK and loss of SAPS3 activates AMPK and protects male mice against overnutrition.

The function of de novo lipogenesis (DNL) in adipocytes has been a mystery as it contributes little to fat storage in these cells. Here, the authors show that DNL is a critical source of fatty acids for membrane-expanding processes like autophagy.

Commensal microbes contribute considerably to mammalian metabolism. Here the authors report the relative contributions of microbiome, age and sex to metabolism throughout the body and uncover age- and sex- specificity in how microbes affect metabolite levels in mice.

Here, the authors identify a novel regulator of autophagy, skeletal muscle mass and integrity named MYTHO. Silencing MYTHO protects against muscle atrophy in a wide range of acute catabolic conditions, while prolonged silencing causes a severe myopathy.

Activation of breathing during hypoxia is abolished in mice lacking mitochondrial complex I in carotid body chemoreceptors, however the specific contribution of mitochondrial complex I to this process is unclear. Here, the authors show that recovery of NADH dehydrogenase activity, but not proton pumping, by transgenic expression of a yeast enzyme rescues cellular and systemic sensitivity to changes in O2 tension.

Gonadotropes in the pituitary secrete follicle-stimulating hormone and luteinizing hormone to control gonadal function and fertility, but whether they exert actions on extra-gonadal organs is not fully understood. Here the authors report that gonadotropes regulate liver steatosis independent of the ovaries in mice.

Time-restricted feeding (TRF) can prevent muscle function decline from obesogenic challenges. Here, the authors reveal that TRF improves muscle function through modulations of common and distinct pathways in diet- and genetic-induced obesity models.

Extracellular vesicles (EVs) convey inter-organ communication in health and disease. Here, the authors report that adipocyte-derived EVs isolated from insulin-resistant obese but not lean male mice stimulate insulin secretion via the targeted transfer of insulinotropic proteins from adipose tissue to β-cells.

β-cell dedifferentiation is a key feature of type 2 diabetes. Here, the authors show evidence of re-differentiation of de-differentiated β-cells and identify ALDH1A3 as a key player in this process, proposing inhibition of ALDH1A3 as a treatment method for β-cell dysfunction in diabetes.

Flavin containing monooxygenase 2 (FMO-2) is known to increase lifespan under dietary restriction through incompletely understood mechanisms. Here the authors report that FMO-2 modifies tryptophan and methionine metabolic pathways to enhance stress resistance and slow aging in C. elegans.

Despite hyperglycemia has been associated to breast cancer, the underlying mechanisms are not completely understood. Here, the authors show that epigenetic regulation of Nrg1 gene during hyperglycemia promotes breast cancer development.

Mitochondrial supercomplex assembly may efficiently supply energy, yet its role remains controversial. Here, the authors show that SYK inhibitors increase supercomplex assembly and mitochondrial respiration in cells and can enhance exercise performance in mice.

Visualizing endogenous GPCRs is challenging. Here the authors generate mice with an enzyme self-label genome-edited into the endogenous glucagon-like peptide-1 receptor locus, design fluorescent dyes for specific labelling in complex tissue, and reveal tissue-level organisation and dynamics of an endogenous class B GPCR.

Although diet modulates aging, little is known about whether and how nutrient regulates longevity. Here, the authors show that glucose-restricted diets prolong longevity through series of conserved factors, such as neuronal AMPK, neuropeptide, AdipoR, PPARα, and Δ9 desaturases by promoting membrane fluidity.

Insufficient glucagon signalling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Here the authors report that the amino acid sensitive calcium sensing receptor (CaSR) is necessary for α cell proliferation via Gq signalling during hyperaminoacidemia.

TPC2 is an important organellar Na⁺/Ca²⁺ release channel which regulates function of lysosomes and lysosome-related organelles. Here, Wang et al. demonstrate that a gain-of-function mutation (R210C) in TPC2 leads to hypopigmentaion, enlarged endolysosomes, enhanced lysosomal Ca²⁺ release and hyper-acidification.

Some forms of mitochondrial dysfunction can cause sterile inflammation, but the way in which it might affect muscle fitness is not well understood. Here, the authors show that altered mitochondrial dynamics can cause the production of mitochondrial DNA-driven inflammatory signals mediated by endosome-mitochondria contacts, leading to muscle inflammation, atrophy, reduced physical performance and enhanced exercise-induced inflammatory responses.

Macrophages have been reported to regulate thermogenic, sympathetic neuron-mediated norepinephrine signaling in adipose tissues. Here the authors report that male mice lacking the allograft inflammatory factor-1 protein are resistant to diet-induced obesity, in association with higher adipose norepinephrine levels and lower expression of the norepinephrine catabolic enzyme monoamine oxidase A.

Based on preclinical studies, gamma aminobutyric acid (GABA) and immunization for the enzyme that produces GABA glutamate decarboxylase (GAD) could be a potential therapy for type 1 diabetes. Here the authors report that in a placebo-controlled, double blind trial in children with new onset type 1 diabetes oral GABA plus GAD did not preserve beta-cell function measured as fasting/meal-stimulated c-peptide levels.

SUMOylation is a mechanism of posttranslational modification involved in eukaryotic cell homeostasis. Here the authors report that mice unable to control SUMOylation in the adrenal cortex develop a selective defect in glucocorticoid production due to disrupted differentiation of cells involved in steroid hormone synthesis.

Food regulates taste perception, but the underlying molecular mechanisms are not clear. Here, the authors reveal that sugar intake in Drosophila induces the gut to secrete Hedgehog into the circulation that suppresses sweet taste, sugar perception and preference.

Dysregulation of the post-translational modification neddylation has been implicated in liver diseases such as fibrosis and hepatocellular carcinoma. Here the authors report that hepatic neddylation deficiency via genetic deletion of NEDD8 Activating Enzyme E1 Subunit 1 (NAE1) causes acute liver failure due to mitochondrial dysfunction and aberrant activation of NF-κB-inducing kinase in mice.

Sirtuins have been reported to positively regulate brown adipose tissue thermogenesis. Here the authors report that brown adipocytic SIRT7 suppresses whole-body energy expenditure and thermogenesis in mice, potentially by attenuating batokine gene expressions and Ucp1 mRNA translation.

The signaling mechanisms regulating adipose thermogenesis have not been fully elucidated. Here, the authors show that a brown fat-enriched adipokine ADISSP promotes adipose thermogenesis and improves metabolic health independently of b-adrenergic receptor.

The role of non-neuronal glial cells in the regulation of adipose tissue function are incompletely understood. Here the authors report that stimulation of mediobasal hypothalamic astrocytes promotes inguinal white adipose tissue lipolysis in mice, dependent on the activation of the pro-opiomelanocortin neurons.

Circadian rhythms are known to impact a range of biological processes including in the immune system. Here the authors show how circadian rhythms modulate the T cell response to vaccination via regulation of dendritic cell metabolism.

Rare variants in the G-protein coupled receptor 151 (GPR151) gene in humans are associated with lower odds ratio for type 2 diabetes, but the mechanism behind this association has remained elusive. Here, the authors show that GPR151 regulates the process of hepatic gluconeogenesis and affects whole-body glucose metabolism.

Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a secreted protein of incompletely understood physiological function. Here the authors show that scEMC10 is upregulated in people with obesity, and that that genetic EMC10 deletion or antibody-based neutralization of EMC10 prevents diet-induced obesity in mice.

Adipose tissue is an important secretory organ, but less is known about the secretory activity of perivascular fat. Here the authors use proteomics analysis on secretomes from perivascular fat to identify neuronal growth regulator 1 as an adipocyte-derived neurotrophic factor, whose decreased secretion in obesity results in a loss of sympathetic innervation of adipose depots in mice.

Here, the authors identify interleukin-11 as a mediator of bone-adipose crosstalk during mechanical loading of the bone. Interleukin-11 secreted by the bone acts as a hormone to regulate fat metabolism, in addition to having an autocrine-paracrine effect on bone itself.

Cells and organisms requires proper membrane composition, which the cell must modulate as membrane lipids are primary acquired from the diet. Here, Ruiz et al. identify a conserved pathway connecting the fluidity regulators AdipoR1/2 with fatty acid desaturase SCD to mediate membrane homeostasis.

Chronic hyperglycemia impairs insulin secretion from pancreatic beta cells in diabetes. Here, the authors reveal that a glucose metabolite is responsible and show lowering glucose metabolism during hyperglycemia prevents loss of beta-cell function.

Environmental temperature changes can alter cell membrane lipid composition but the mechanisms underlying this conserved mechanism are unclear. Here, the authors identify the megaprotein LPD-3 in C. elegans as critical for normal phospholipid distribution and cold resilience.

Parkin plays a role in mitophagy and has been shown to control adipose tissue browning and thermogenesis. Here the authors report that Parkin coordinates mitophagy with Pgc1α-mediated mitochondrial biogenesis in white adipocytes to regulate adiposity.

Mitochondrial networks are carefully positioned to facilitate energy distribution within muscle cells. Here they show that energetic demands and conserved transcription factors regulate mitochondrial network organization and contractile phenotypes independently in Drosophila.