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Metformin treatment was found to be associated with acute increases in the appetite-suppressing metabolite Lac-Phe in several human observational and interventional studies.
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.
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.
Zhang, Fang, et al. develop a method to perform an in-depth lysine succinylation analysis in the mouse liver. This approach allows them to identify a previously unappreciated mechanism of regulation of the urea cycle and ammonia detoxification.
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.
In male mice with diet-induced obesity, deletion of insulin inhibitory receptor (inceptor) in the whole body, in the brain and in pancreatic β cells improves glucose homeostasis, underlining a role of inceptor in regulating glucose homeostasis in the brain and pancreas.
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.
The authors show that abnormal elevation of osteocyte-derived sclerostin deregulates Wnt–β-catenin signalling in the brain and aggravates cognitive impairment under pathological conditions.
In a randomized placebo-controlled trial in 37 individuals with excess body weight, dietary supplementation with resistant starch lowers body weight and induces changes in gut microbiota composition. Mechanistic analysis in male mice shows that resistant starch at least partially facilitates weight loss through the action of Bifidobacteriumadolescentis.
In the context of succinate uptake to promote adipose tissue browning, Reddy, Winther et al. show how the directionality of succinate transport across membranes is coupled with metabolic flux-derived changes in pH gradients.
De Solis and Del Río-Martín et al. investigate the reciprocal interplay between AgRP and POMC neurocircuits that governs the precise regulation of food intake and systemic metabolic homeostasis.
Zhang et al. use human studies and mechanistic work in mouse models to describe how leucine serves as the key amino acid derived from dietary protein to drive deleterious macrophage mTORC1 signalling and promote cardiovascular disease.
Tighanimine et al. perform integrative time-resolved transcriptome and metabolome analysis in senescent cells and find that glycerol-3-phosphate and phosphoethanolamine accumulate and rewire lipid metabolism to promote senescence.
Lee, Park et al. show that selenium has the ability to directly regulate the redox state of ubiquinone by donating electrons from hydrogen selenide via sulfide quinone oxidoreductase, thus preventing lipid peroxidation.
Ramachandran et al. identify a previously unappreciated function for transcriptional repressor B cell lymphoma 6 (BCL6) in muscle proteostasis and strength, and provide mechanistic insight into the molecular underpinnings of this function.