Volume 3 Issue 3, March 2021

It is self-evident that consuming alcohol affects brain function and behaviour. What is not clear, however, is how alcohol does so. A new study shows that impairments in balance and motor coordination evoked by low-dose alcohol are mediated not by ethanol itself but by one of its metabolites, which is produced locally by astrocytes in the brain rather than in the liver.

Obesity is associated with mitochondrial dysfunction and chronic metabolic derailment. Cho et al. report that elevated adipose expression of the Hippo kinases STK3 and STK4 (STK3/4) in obesity and type 2 diabetes decreases the mass and oxidative capacity of adipocyte mitochondria. Genetic or pharmacological inhibition of STK3/4 restores mitochondrial mass and function in adipocytes and improves glucose homeostasis in mice with diet-induced obesity. These findings support STK3/4 as new targets for obesity-related diseases.

Nutrient availability dictates cell differentiation and transition through the Dictyostelium discoideum life cycle. Kelly et al. reveal that the increase in reactive oxygen species associated with nutrient limitation coincides with a sequestration of available cysteine in glutathione, thus limiting sulfur-dependent mitochondrial respiration and promoting aggregation into the differentiated spore form.

Quarta et al. discuss POMC neuronal heterogeneity and how specific subpopulations of POMC neurons can have diverse effects on appetite, whole-body metabolic physiology and the development of obesity.

Flippo and Potthoff provide a concise overview of the major physiological and pharmacological effects of FGF21 in nutrient and energy homeostasis.

In a screen of peripheral blood cells from fasted or fed individuals, Han et al. identify FOXO4 and its target FKBP5 as fasting-induced modulators of CD4⁺ T helper cell responsiveness.

Glycogen accumulation is a hallmark of clear cell renal cell carcinoma. Xie et al. uncover that under metabolic stress or hypoxia, these glycogen deposits are dispensable for tumour cell proliferation and survival, both in vivo and in vitro.

Jin et al. show that astrocytic ALDH2 metabolizes ethanol in the brain, thereby attributing behavioural effects of alcohol to metabolites produced in the brain rather than the liver.

Zhao et al. use genetic lineage tracing to demonstrate that pancreatic endocrine and exocrine progenitor cells do not generate new beta cells, thus arguing against beta-cell neogenesis in the adult mouse pancreas.

Rare variants in the gene encoding PHGDH, the rate-limiting enzyme in de novo serine biosynthesis, are identified as responsible for serine deficiency associated with the macular degenerative disease MacTel.

Insulin stimulates TUG cleavage to translocate GLUT4 and enhance glucose uptake. Here Bogan and colleagues show that the TUG cleavage product regulates thermogenic gene transcription, thereby coupling glucose uptake to organismal energy expenditure.

Elevated hepatic alanine catabolism is shown to promote hyperglycaemia and reduce skeletal muscle protein synthesis, thereby linking sarcopenia with hyperglycaemia in the context of type 2 diabetes.

Kim et al. reveal that TFEB expression is protective in the setting of diet-induced obesity by activating the expression of GDF15 in adipose tissue macrophages in mice and humans.

Cho et al. show regulation of mitophagy, and thereby energy expenditure, in adipocytes by the Hippo pathway kinases STK3 and STK4, independently of classical Hippo signalling. Genetic inactivation of Stk3 and Stk4 is shown to protect mice from the adverse metabolic effects of diet-induced obesity.