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Healthy white adipose tissue is dependent on the proliferation of endothelial cells to maintain homeostasis or undergo expansion. A new study shows that endothelial cells communicate with adipocytes via polyamines to promote vascularization of adipose tissue, thereby reversing the metabolic effects of obesity.
GDF15 is a hormone with the potential to regulate energy intake. GDF15 signals via the GFRAL/RET receptor complex, and besides the ligand activation of the receptor complex, our knowledge on control of receptor signalling is limited. Chow et al. show that MT1-MMP controls GDF15 actions by regulating levels of GFRAL.
Although glucose classically serves as the main neuronal fuel source in the brain, Silva et al. demonstrate that ketones produced by local glial cells are critical for memory formation in starving flies. Here we discuss the implications of these findings for aging, neurodegeneration and the genetics of ketone metabolism.
The creatine/phosphocreatine system is known to have diverse functions in various tissues. Maqdasy, Lecoutre and colleagues reveal a new role, namely, regulating the development of obesity-induced inflammation in white adipocytes.
Enzyme–enzyme interactions are largely assumed to act co-operatively to render biochemical pathways more efficient. However, under stress the glutamate synthase of B. subtilis does the exact opposite: it inhibits glutamate degradation by sterically hindering the activity of glutamate dehydrogenase.
Facchinello, Astone et al. demonstrate a role for the endothelial oxidative pentose phosphate pathway (oxPPP) in promoting vascular mural cell coverage and maturation during early development by regulating elastin expression. This mechanism establishes a critical role for oxPPP in the formation of the vascular system.
Circulating metabolite levels are our window into physiological homeostasis. Beyond glucose, our understanding of how homeostasis is maintained for other major metabolites is less developed. Li et al. demonstrate that for most major circulating metabolites, there is a linear relationship between breakdown in the TCA cycle and systemic levels, and thus mass-action-driven oxidation is a major regulator of systemic metabolite levels.
Obesity is commonly associated with leptin resistance. Inhibition of HDAC6 in adipose tissue of mice with diet-induced obesity produces a protein factor that augments leptin’s ability to reduce feeding and body weight, and improve glucose tolerance. HDAC6 inhibition acts as a novel treatment for obesity by ameliorating leptin resistance.
De novo adipocyte differentiation ensures healthy adipose tissue expansion and protects against deleterious ectopic lipid deposition in the setting of overnutrition. Dong and Sun et al. identify a molecular brake on adipogenesis that may contribute to the development of insulin resistance in obesity.
How pathogens induce life-threatening symptoms in some individuals but not others is one of the greatest puzzles in biology. Pruss et al. have discovered that the presence of the amino acid ornithine fuels the persistence of the bacterial pathogen Clostridioides difficile in the absence of disease.
Severe COVID-19 is often associated with detrimental elevations in blood glucose, but the mechanisms are poorly understood. In this issue of Nature Metabolism, Wan et al. identify GP73 as a SARS-CoV-2-induced secreted factor that enhances hepatic glucose production and is necessary for SARS-CoV-2-associated glucose abnormalities.
