Astrocytes are brain cells that react to Alzheimer’s disease pathology in ways that can have either beneficial or detrimental effects. In this issue of Cell Metabolism, Ju et al. outline a novel strategy for coercing astrocytes to a neuroprotective state by maintaining liver-like detoxification in the brain without producing damaging byproducts.

Obesity is linked to inflammation and downstream metabolic dysregulation. In this issue of Cell Metabolism, Hägglöf et al. show that iNKT cells enable the accumulation of T-bet+ B cells in white adipose tissue, which in turn produce chemokine and antibody mediators that exacerbate the onset and severity of metabolic disease.

Disorders of carbohydrate metabolism, including hypoglycemia and lactic acidosis, are common features of malaria. In this issue of Cell Metabolism, Ramos et al. report that regulation of gluconeogenesis and glycemia by the host glucose-6-phosphatase catalytic subunit 1 (G6Pc1) is a key metabolic step that affects both Plasmodium replication and clinical outcome of disease.

Lactate released from skeletal muscle during high-intensity exercise gives rise to a surge in circulating lactate-derived pseudo-dipeptide metabolites including N-lactoyl-phenylalanine (Lac-Phe). In a recent Nature paper, Li et al. use genetic and pharmacological evidence to now propose Lac-Phe to be an “exercise hormone” that suppresses appetite and obesity.

Obesity is accompanied by inflammation in adipose tissue, impaired glucose tolerance, and changes in adipose leukocyte populations. These studies of adipose tissue from humans and mice revealed that increased frequencies of T-bet+ B cells in adipose tissue depend on invariant NKT cells and correlate with weight gain during obesity. Transfer of B cells enriched for T-bet+ cells exacerbates metabolic

Abstract not available

Abstract not available

The cephalic phase of insulin secretion (CPIS) plays a crucial role in glucose homeostasis. However, the neural basis of CPIS and its overall relevance to metabolic health are poorly understood. Here, we preview the findings of Wiedemann et al. (2022) that address the role of IL-1β in the integration of neuro-mediated insulin release following cephalic stimulation and CPIS dysregulation in obesity

Obesity-induced type 2 diabetes, or diabesity, is associated with ER stress, UPR activation, and insulin resistance through poorly understood mechanisms. Herrema et al. (2022) report that the XBP1 target FKBP11 is repressed in the obese mouse liver and that its re-expression activates a protective UPR pathway that restores insulin sensitivity.

Tumor-supporting roles of ammonia have gained greater appreciation in recent years and normally focus on ammonia’s role as a nitrogen source. Recently in Nature Metabolism, Cheng et al. (2022) demonstrate a novel, non-nitrogen, metabolism-related role of ammonia as a key activator for lipogenesis by facilitating SREBP-1 activation.

In this review, we focus on recent developments in our understanding of nutrient-induced insulin secretion that challenge a key aspect of the “canonical” model, in which an oxidative phosphorylation-driven rise in ATP production closes KATP channels. We discuss the importance of intrinsic β cell metabolic oscillations; the phasic alignment of relevant metabolic cycles, shuttles, and shunts; and how

In this issue of Cell Metabolism, Liu et al. demonstrate that Prmt7 can regulate the onset and progression of leukemogenesis by inhibiting self-renewal capacity of leukemic stem cells (LSCs) as modeled in a murine version of chronic myeloid leukemia (CML).

Mammalian lifespans are dramatically diverse. Identifying the molecular signatures and underlying mechanism of longevity is of keen interest. Using comparative transcriptomics, Lu et al. (2022) showed that genes associated with maximum lifespan are regulated by circadian and pluripotency networks, which shed light on natural strategies for controlling lifespan.

Genetics in model organisms has progressively broken down walls that previously separated different disciplines of biology. One example of this holistic evolution is the recognition of the complex relationship that exists between the control of bone mass (bone remodeling) and energy metabolism in mammals. Numerous hormones orchestrate this crosstalk. In particular, the study of the leptin-mediated

Abstract not available

Abstract not available

Adipose tissue has been linked to inflammation and various physiological processes. In this issue of Cell Metabolism, Caputa et al. describe that perinodal adipocytes adapt their metabolism to actively participate in an immune response against intracellular Listeria monocytogenes.

In a recent issue of Nature, Arnold et al. report that the partitioning of citrate away from the oxidative steps of the tricarboxylic acid cycle and into the citrate-malate shuttle is essential for mouse embryonic stem cell differentiation. Their findings highlight a crucial role for metabolic regulation in developmental biology.

We investigate the extent to which human genetic data are incorporated into studies that hypothesize novel links between genes and metabolic disease. To lower the barriers to using genetic data, we present an approach to enable researchers to evaluate human genetic support for experimentally determined hypotheses.

In this issue of Cell Metabolism, Hochrein et al. identify a metabolic checkpoint controlling the transcriptional programming of effector CD4+ T cells. The authors show that GLUT3-mediated glucose import and ACLY-dependent acetyl-CoA generation control histone acetylation and, hence, the epigenetic imprinting of effector gene expression in differentiated effector CD4+ T cells. These findings suggest

Immunotherapy has limited success in triple-negative breast cancer (TNBC). In this issue of Cell Metabolism, Wang et al. found that microbial metabolite TMAO boosts CD8+ T cell-mediated antitumor immunity by inducing pyroptosis in tumor cells, enhancing the efficacy of immunotherapy in TNBC (Wang et al., 2022).

Extracellular vesicles (EVs) and their cargo act as signaling moieties by transferring their cargo to recipient cells, thereby mediating intercellular communication in complex tissue environments such as the tumor microenvironment. In the accompanying paper, Kudo et al. describe the interaction between tumor EVs and soluble phospholipase released by macrophages, leading to the remodeling of EV membranes

The microbiome in arguably sterile tissues has received considerable attention in the last few years. A recent report by Leinwand and colleagues disentangles host-microbe interactions in the mammalian liver. The authors demonstrate that a distinct liver microbiome controls hepatic immune responses in mice, challenging the perception of a sterile liver.

In a recent paper in EMBO Molecular Medicine, Weis et al. reveal that cardiac endothelial cells can oxidize ketone bodies, which enhances cell proliferation, migration, and vessel sprouting. Furthermore, increasing ketone body levels with a ketogenic diet can increase endothelial cell proliferation and prevent blood vessel rarefication in hypertrophied mouse hearts. This suggests that increasing endothelial