Volume 1 Issue 11, November 2019

Lifespan is increased and ageing is delayed by lifelong dietary restriction. A study in Nature Metabolism shows that these benefits are reduced when dietary restriction is started in old age, owing to the development of an inflexible nutritional memory within white adipose tissue.

A new study by Menegaz et al. in this issue of Nature Metabolism addresses fundamental questions on the acute regulation and role of GABA secretion in pancreatic islets.

A study in Nature Metabolism reveals a hitherto-unknown enzymatic and physiological role of ABHD5, which acts as a protease that couples extracellular cues to the epigenome of cardiomyocytes by cleaving histone deacetylase 4 (HDAC4).

The mechanism of alcohol-induced changes in the brain is multi-faceted. Acetate, the product of hepatic alcohol metabolism, might contribute to addictive behaviour by regulating gene expression.

Generally, most metabolic diseases are not caused by a mutation or defect in a single gene but instead are multi-factorial, resulting from a combination of genetic and environmental factors; thus, studying them requires a holistic approach. Here, Seldin and colleagues review systems genetics approaches, including their resources and advantages, for studying metabolic diseases.

Ceramides are bioactive lipids that regulate cellular signalling processes and metabolic pathways, and are implicated in various metabolic diseases. Here, Summers, Chaurasia and Holland provide a concise overview of the history of ceramides and their physiological roles, mechanisms of action and therapeutic potential.

Dietary restriction (DR) late in life does not improve survival and has little benefit in metabolic health in mice. The absence of a DR gene-expression signature in fat tissue suggests that a ‘nutritional memory’ interferes with the benefits of DR.

In addition to having direct anti-cancer effects, the cardiac glycoside ouabain is shown to kill a broad range of senescent cells, thus suggesting that cardiac glycosides represent a novel class of senolytics.

Emerging findings identify important roles for brain lipoprotein receptors in the control of whole-body energy homoeostasis. Here Lee et al. reveal that IDOL-mediated regulation of VLDLR abundance in neurons, but not in peripheral metabolic tissues, regulates food intake and energy expenditure.

Al Nabhani et al. show how excessive caloric intake during the postnatal period increases the risk of developing intestinal bowel disease during adulthood, owing to increased intestinal permeability, cytokines and hydrogen sulfide production by the microbiota.

Pulsatile GABA secretion from human beta cells via the volume regulatory anion channel (VRAC) and subsequent uptake by the GABA-permissive taurine transporter (TauT) is shown to regulate total insulin secretion and pulsatility.

Lipid degradation by autophagy is shown to drive mTORC1 hyperactivation in neural stem cells from Tsc1-deficient mice.

Liu et al. describe a molecular network wherein SIRT7 couples light-driven systemic body temperature cues to hepatic oscillators via HSP70 to ensure circadian phase coherence and glucose homeostasis in the liver.

Known as a regulator of lipolysis, ABHD5 is found to also act as a serine protease that cleaves HDAC4 in response to catecholaminergic stimulation, thus resulting in the formation of a polypeptide that protects against metabolic-stress-induced heart failure.