Reviews & Analysis

The loss of T cell immune function as a result of human immunodeficiency virus (HIV) infection leads to opportunistic infections and certain HIV-associated cancers. Two recent studies shed light on the complex immunometabolic changes during HIV infection and open the door to metabolic treatment options that could ultimately cure HIV.

A multi-faceted translational study provides the first evidence that gut microbial conversion of lactate to propionate may enhance athletic performance during high-intensity endurance exercise.

The entry of remnants of cholesterol-rich lipoproteins, such as low-density lipoprotein (LDL), from the blood stream into the intima of large arteries initiates and then perpetuates atherosclerosis. A study published in Nature sheds new light on this important process by identifying scavenger receptor BI (SR-BI) as a major receptor that mediates LDL delivery across the endothelium into arteries.

Living organisms face the dual challenge of acquiring enough iron to perform biological functions while preventing toxic iron accretion. A study now shows that sensing of iron-catalysed free radicals by a druggable gene-regulatory pathway helps the body avoid iron poisoning.

Interorgan communication is emerging as a critical contributor to nutrient and energy homeostasis. A new study has identified a secreted liver factor that stimulates lipid synthesis in white adipose tissue and exacerbates obesity and insulin resistance.

A common missense variant (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) was strongly linked to human fatty liver disease in 2008, but the underlying mechanisms have since remained unclear. Compelling data from Yang et al., published in Nature Metabolism, suggest that PNPLA3 binds ABHD5, sequestering it and preventing it from activating ATGL, the major intracellular triglyceride lipase.

Increasing pancreatic β-cell proliferation in autoimmune type 1 diabetes (T1D) might restore β-cell mass but would be predicted to exacerbate islet inflammation. A study in Nature Metabolism, however, reports that boosting β-cell proliferation in mouse models of T1D is beneficial, preserving the immunological self-tolerance of islets through the induction of regulatory T cells.

Obesity is a manifestation of a positive energy balance in which energy intake exceeds energy expenditure, thus often leading to insulin resistance and type 2 diabetes. A new study provides evidence that pharmacological inhibition of hyaluronan, an extracellular-matrix glycosaminoglycan, increases energy expenditure and insulin sensitivity by activating thermogenesis in brown adipose tissue.

Understanding the mechanisms by which tumour cells adapt or succumb to targeted therapies is crucial to improving cancer treatment. A study in this issue of Nature Metabolism demonstrates how microRNAs, metabolic pathways and pseudohypoxia play a major role in the drug tolerance to epidermal growth factor receptor (EGFR) inhibitors in lung adenocarcinoma.

A recent large genetic study by Sanna et al., published in Nature Genetics, has shown that short-chain fatty acids, which are produced by gut microbes, have a significant causal effect on insulin secretion, postprandial glycaemic responses and risk of type 2 diabetes.

As one of the most highly consumed amino acids in cultured cancer cells, glutamine is an attractive target for anti-cancer therapy, and glutaminase inhibitors are currently in clinical trials. In this issue, Ni et al. show that blocking this pathway by targeting the glutamine importer ASCT2 (SLC1A5) decreases tumorigenesis in mouse leukaemia models while largely sparing normal haematopoiesis.

Patients with severe diabetes rely on insulin injections to control their blood glucose. A study now provides evidence that human cells that normally do not release insulin can be converted into insulin-producing cells that are able to normalize glycaemia in diabetic mice.

The senescence-associated secretory phenotype (SASP) is responsible for the deleterious effects of senescent cells in ageing and cancer. A new study shows that NAD⁺ metabolism can regulate the pro-inflammatory SASP, thereby promoting tumorigenesis.

A new study in C. elegans identifies a microRNA-dependent mechanism that enables olfactory neurons to rapidly regulate protein degradation in the intestine and therefore organismal ageing.

Hypothalamic neuronal diversity is at the core of whole-body energy-homeostasis control, but the molecular mechanisms governing neuronal neuropeptide specification remain incompletely understood. A new study in Nature Metabolism adds a relevant piece to the puzzle of how key hypothalamic neuronal populations maintain their peptidergic identity throughout the lifespan.

The circulatory system in long bones is incompletely understood. A new study published in Nature Metabolism unveils the presence of dense vascular networks in long bones that facilitate the egress of bone marrow cells and potentially the exchange of nutrients between the bone marrow and the systemic circulation.

Strategies to restore levels of the enzyme cofactor nicotinamide adenine dinclueotide (NAD) late in life to maintain health by treatment with NAD precursors, such as nicotinamide mononucleotide (NMN), represent an exciting area of research in aging and age-related diseases. A study in Nature Metabolism provides an answer to the hotly debated yet fundamental question: how NMN actually gets into cells.

Fibrosis is characterized by excessive extracellular matrix (ECM) production relative to catabolism. A new study shows that the fuel choice of fibroblasts impacts this balance, with glycolysis promoting ECM synthesis and fatty acid oxidation stimulating ECM degradation.

The growth of new blood vessels (angiogenesis) is a bio-energetically demanding process. Surprisingly, the specific role of mitochondria in angiogenesis remains unclear. A study in this issue of Nature Metabolism now demonstrates that mitochondrial respiration is essential for angiogenic growth by controlling endothelial proliferation.

Cholesterol accumulation in cells and blood vessels promotes the development of vascular diseases. The long non-coding RNA CHROME can help clear excess cholesterol and provide protection from atherosclerosis.