Volume 1 Issue 3, March 2019

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.

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.

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.

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.

Activation of tissue-resident myeloid cells in the brain, known as microglia, is thought to drive obesity-associated hypothalamic dysfunction. The authors of this Perspective present a more nuanced view of microglia, echoing lessons learned from the field of adipose macrophage biology: instead of simply responding to diet-induced damage, microglia are proposed to act as nutrient and environmental sensors that regulate hypothalamic physiology, a role that, if hijacked by chronic overnutrition, can produce disease.

The protein kinase complex mechanistic target of rapamycin complex 1 (mTORC1) is a key cellular nutrient and energy sensor that integrates several inputs to regulate cell growth. Here, the authors discuss the molecular logic of the mTORC1 signalling network and its importance in coupling growth signals to the control of cellular metabolism.

Secreted from adipocytes, adiponectin exerts primarily anti-apoptotic, antiinflammatory, anti-fibrotic and insulin-sensitizing activities on multiple tissues. Here, Straub and Scherer provide a concise overview of the history of adiponectin, its physiological role and molecular mechanism of action.

AMPK is a master regulator of cellular metabolism. Here the authors show that a constitutively active AMPK mutation protects mice fed a high-fat diet from obesity by increasing energy expenditure in subcutaneous white adipocytes, possibly as a result of the emergence of a hitherto-unknown type of adipocyte.

Olfactory food perception is known to extend lifespan in C. elegans. Here the authors demonstrate food-odour-dependent brain-to-gut communication that extends lifespan in worms. Food odour downregulates tir-1 mRNA in AWC neurons, in a manner dependent on the miRNA miR-71, which triggers downstream effects in the gut, due to neuropeptide secretion, that promote proteostasis and longevity.

Creatine can be used for thermogenesis in adipocytes. Here Kazak et al. show that creatine uptake is required to sustain this thermogenic pathway. Knockdown of the creatine transporter, CrT, in adipocytes decreases thermogenesis and energy expenditure, whereas creatine supplementation increases energy expenditure in mice fed a high-fat diet.

Obesity is associated with an increased risk of colitis-associated cancer (CAC). Here Ostermann et al. show that a high-fat diet induces insulin resistance in intestinal epithelial cells (IECs) and that genetic inactivation of insulin and IGF1 signalling in IECs impairs intestinal regeneration and enhances tumour formation in a CAC mouse model.

Amino acids are required for cell survival and growth. However, the different requirements of amino acid metabolic pathways in normal haematopoiesis and leukaemogenesis have not been explored. Here the authors focus on the transporter of neutral amino acids and show that malignant blood cells rely more on ASCT2-mediated amino acid metabolism than normal cells.

The oxidative pentose-phosphate pathway (oxPPP) is a major NADPH producer. Here the authors show that malic enzyme or isocitrate dehydrogenase can support the growth of cells lacking the oxPPP, but the oxPPP is necessary to maintain a normal NADPH/NADP ratio, DHFR activity and folate metabolism.