Volume 6 Issue 4, April 2024

Non-alcoholic liver disease (NAFLD) is now metabolic dysfunction-associated steatotic liver disease (MASLD), emphasizing the key metabolic factors of obesity, insulin resistance, vascular dysfunction and dyslipidaemia. Here, we discuss impacts on the existing body of clinical and preclinical liver disease research and on research moving forward.

The mechanism by which metformin affects food intake remains controversial. Now, two studies link metformin treatment with the induction of the appetite-suppressing metabolite N-lactoyl-phenylalanine, which is produced by the intestine.

The microbiome is implicated in a study that involves the metabolism of dietary fibre into short-chain fatty acids, which provides a biochemical link to the poorly understood histone butyrylation.

The mechanisms that drive cancer cachexia are unclear. Adipocyte activation of GPR81 by high levels of lactate is now shown to drive adipose tissue browning, thermogenesis and a loss of body weight in mouse models of cancer.

In this issue of Nature Metabolism, it is shown that the abundance of Caenorhabditis elegans branched-chain aminotransferase-1 (BCAT-1) — which catalyses the first step of branched-chain amino acid (BCAA) catabolism — declines sharply in aged wild-type nematodes but not in slowly ageing mutants, and that stimulating BCAA catabolism extends reproductive longevity.

In this study in humans, the authors describe distinct phases of adaptions in the plasma proteome to seven days without food, and identify limited associations of protein changes with weight loss.

A new sensor that detects optoacoustic signals generated by mid-infrared light enables measurement of glucose concentration from intracutaneous tissue rich in blood. This technology does not rely on glucose measurements in interstitial fluid or blood sampling and might yield the next generation of non-invasive glucose-sensing devices for improved diabetes management.

Yurdagul and colleagues offer an integrated picture of metabolic changes at the cellular and at the lesion level in atherosclerosis.

Sinha and Yen provide a comprehensive overview of thyroid hormones and their role in development and in regulation of whole-body metabolic homeostasis

Metformin treatment was found to be associated with acute increases in the appetite-suppressing metabolite Lac-Phe in several human observational and interventional studies.

Metformin is shown to trigger production and release of Lac-Phe from gut epithelial cells, which is required for its effects on food intake and loss of body weight.

This study addresses the hypothesis of dietary glucose handling in humans through a postprandial lactate shuttle.

A new methodology uses intravital time-gated mid-infrared optoacoustic signals for accurate non-invasive measurements of glucose concentrations in blood-rich volumes of the skin.

The authors report a genetic screening method that preserves mitochondrial physiology under cell permeabilization, which allows in-depth genetic dissection of mitochondrial bioenergetics.

Gates et al. show that histone butyrylation and propionylation in the intestinal epithelium are regulated by the gut microbiota and histone butyrylation is associated with gene regulatory programmes.

Tumour-derived lactate activates adipose GPR81, which in turn leads to cachexia. Targeting GPR81 and its downstream signalling pathway holds therapeutic potential for treating cancer cachexia.

Lesnik, Kaletsky et al. show that in C. elegans branched-chain amino acid catabolism is important for maintaining oocyte quality with age.

Sun et al. identify fatty acid binding protein 5 (FABP5) as a driver of obesity-induced hepatocellular carcinoma in mice. FABP5 inhibition is found to predispose transformed cells to death by ferroptosis and to induce a pro-inflammatory tumour microenvironment.

The authors describe distinct phases of adaptions in the human plasma proteome to 7 days without food, with profound changes occurring only after 2 days.