The gut microbiota is implicated in immune system functions. Regulation of the metabolic processes occurring in immune cells is crucial for the maintenance of homeostasis and immunopathogenesis. Emerging data demonstrate that the gut microbiota is an actor in immunometabolism, notably through the effect of metabolites such as short-chain fatty acids, bile acids, and tryptophan metabolites. In this

SARS-CoV-2 pneumonitis can quickly strike to incapacitate the lung, leading to severe disease and sometimes death. In this perspective, we suggest that vitamin D deficiency and the failure to activate the vitamin D receptor (VDR) can aggravate this respiratory syndrome by igniting a wounding response in stellate cells of the lung. The FDA-approved injectable vitamin D analog, paricalcitol, suppresses

Metabolic dialogue between tumors and their microenvironment emerges as a key regulator of chemoresistance, the major barrier for the treatment of several cancers. In this issue of Cell Metabolism, van Gastel et al. decipher the pivotal role of stromal glutamine-derived aspartate to sustain pyrimidine biosynthesis in chemoresistant acute myeloid leukemia (AML) and thus state it as a target for anti-cancer

In this issue of Cell Metabolism, Asadi Shahmirzadi et al. (2020) demonstrate that late-onset dietary supplementation with calcium alpha-ketoglutarate results in increased survival, compressed morbidity, and reduced frailty in mice. The study provides further evidence for critical links between metabolism, inflammation, and aging.

In this issue of Cell Metabolism, Balmer et al. show that the timing and concentration of acetate exposure is critical to how it is metabolized by and affects the function of CD8 T cells. When abundantly present at the time of reactivation, acetate rewires CD8 T cell metabolism to suppress their reactivation and limit inflammation.

Macrophages are central to the pathogenesis of non-alcoholic steatohepatitis (NASH). However, the identities and functional relationships between tissue-resident and tissue-recruited macrophages in NASH remain poorly understood. A recent study from Seidman et al. (2020) elucidates, at single-cell resolution, the fates, niches, and regulatory landscapes of liver tissue-resident and tissue-recruited

Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL

In this essay, we highlight how litter size in rodents is a strong determinant of neonatal growth and long-term metabolic health. Based on these effects, we strongly advise that scientific articles that utilize rodent models for obesity and metabolic research should include information on the litter sizes in the study to increase the data transparency of such reports.

Recent evidence in humans and mice supports the notion that mitochondrial metabolism is active and necessary for tumor growth. Mitochondrial metabolism supports tumor anabolism by providing key metabolites for macromolecule synthesis and generating oncometabolites to maintain the cancer phenotype. Moreover, there are multiple clinical trials testing the efficacy of inhibiting mitochondrial metabolism

HIF is a transcription factor that plays an essential role in the cellular response to low oxygen, orchestrating a metabolic switch that allows cells to survive in this environment. In immunity, infected and inflamed tissues are often hypoxic, and HIF helps immune cells adapt. HIF-α stabilization can also occur under normoxia during immunity and inflammation, where it regulates metabolism but in addition

The COVID-19 pandemic has driven unprecedented efforts to identify existing treatments that can be quickly and effectively repurposed to reduce morbidity and mortality. In this issue of Cell Metabolism, Zhang et al. (2020) report an association between statin use and improved outcomes in a large observational study of hospitalized COVID-19 patients. Given the widespread availability, low cost, and

iNKT cells are important regulatory cells in metabolic health and disease. In this issue of Cell Metabolism, LaMarche et al. (2020) clarify the origin and heterogeneity of these unconventional T cells and identify the specific signals in adipose tissues that direct their function.

The precise mechanisms of free fatty acid (FFA) uptake in the vascular endothelium are unclear. In this issue of Cell Metabolism, Ibrahim et al. (2020) discover that FFA uptake is partially mediated by a vectorial, ER-mitochondria link, in which mitochondrial ATP production is locally used for the acyl-CoA synthetase activity of the ER-located fatty acid transport protein 4.

Psychological stress has long been known to reduce adaptability to inflammatory challenges, although the precise mechanism has remained elusive. In a recent issue of Cell, Qing et al. (2020) demonstrate that psychological stress induces secretion of IL-6 from brown adipose tissue, which promotes hepatic gluconeogenesis, and reduces host fitness to inflammatory insults.

Amino acids are fundamental building blocks supporting life. Their role in protein synthesis is well defined, but they contribute to a host of other intracellular metabolic pathways, including ATP generation, nucleotide synthesis, and redox balance, to support cellular and organismal function. Immune cells critically depend on such pathways to acquire energy and biomass and to reprogram their metabolism

Bharath et al., 2020 report that CD4+ T lymphocytes from aged individuals exhibit defective mitochondrial autophagy, resulting in altered redox metabolism and upregulation of TH17 cytokines, which in turn may contribute to aging-associated chronic inflammation or “inflammaging.” Of note, the antiaging drug metformin reverses this autophagy defect and rejuvenates CD4+ T cell function.

The abundance of dietary sweeteners and overconsumption of fructose are widely thought to promote metabolic disease. In this issue of Cell Metabolism, Andres-Hernando et al. (2020) identify the liver as the major site of fructose metabolism-mediated metabolic dysfunction and identify a surprising role for intestinal fructose metabolism in driving fructose intake.

In a recent issue of Cell, Orthofer et al. (2020) present a body of data from mice, flies, and humans that suggest (1) a physiological role for Alk in the normal control of energy balance across several species and (2) a possible contribution of genetic variants in or near ALK to the variability of adiposity in humans, more specifically at its lower end.

Recent quantitative mass spectrometry and coexpression network analysis of postmortem human brain samples identified protein networks responsible for sugar metabolism and function of astrocytes and microglia are altered in Alzheimer’s disease and other types of neurodegenerative disorders. Boosting neuroglial function may represent a new strategy for containing neurodegeneration.

Recent studies have shown impressive cardiovascular health benefits in individuals treated with SGLT2 inhibitors (SGLT2i) regardless of diabetic status. The underlying mechanisms driving these benefits are not well understood. Recently in Circulation, Griffin et al. (2020) reported the first human study investigating the diuretic effect of empagliflozin.

The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of