News and thoughts
Burning fat with cysteine depletion
Brittney Adams1, Stanislaw Walkowiak1 and Mohammed K Hankir1
Adams and colleagues comment on two complementary articles by Varghese et al and Lee et al showing that cysteine depletion through combined dietary and genetic means in mice evokes a unique stress response in the liver to amplify these metabolic outcomes and offer a potentially new treatment option for obesity.
Pathogenic hyperactivation of mTORC1 by cytoplasmic EP300 in Hutchinson-Gilford progeria syndrome
Lucille Ferret1,2,3, Guido Kroemer1,2,4 and Mojgan Djavaheri-Mergny1,2
Mechanistic target of rapamycin complex 1 (mTORC1) is a multiprotein complex that serves as a pivotal regulator of cell growth, protein synthesis, metabolism and autophagy [1][2]. This complex compromises mTOR
Gut microbiota turn up the heat after bariatric surgery
Mohammed K. Hankir1
Bariatric surgeries like vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) cause well-established shifts in the gut microbiota, but how this contributes to their unique metabolic benefits is poorly understood. Jin et al and Yadav et al now provide two complementary lines of evidence suggesting that gut microbiota-derived metabolites after VSG and RYGB activate thermogenesis in fat through distinct mechanisms, to in turn promote weight loss and/or improvements in glycemic control.
Novel insights at the crossroads of antibiotic use and cancer risk
Nermina Malanovic1,2,3 and Djenana Vejzovic4
The continuous use of antibiotics is associated with the spread of antimicrobial resistances and the not yet clear link to cancer development. Many conventional antibiotics have already shown different effects on a variety of cancer types raising questions for their rational use in cancer. However, discrepancy in the observed trend for some antibiotics reducing cancer development and being associated with higher risk of cancer underscores the lack of understanding the complex link between antibiotics and cancer. Here, we briefly summarize the possible antibiotic-mediated effects on cancer and conclude that those effects can be direct via i) specific targeting of tumor/cancer, ii) antimicrobial activity and iii) immunomodulatory activity whereby iv) indirectly caused effects primarily affect immune equilibrium between bacteria, cancer and immune cells. Furthermore, we also conclude that there is a great need for bulk profiling, comprehensive screening programs in all countries and in-depth studies to understand the risks and benefits of antibiotic use.
Cardiac PI3K p110α attenuation delays aging and extends lifespan
Mahmoud Abdellatif1,2,3,4, Tobias Eisenberg4,5,6, Alexander Martin Heberle7, Kathrin Thedieck7,8,9, Guido Kroemer2,3,10 and Simon Sedej1,4,11
Phosphoinositide 3-kinase (PI3K) is a key component of the insulin signaling pathway that controls cellular me-tabolism and growth. Loss-of-function mutations in PI3K signaling and other downstream effectors of the insulin signaling pathway extend the lifespan of various model organisms. However, the pro-longevity effect appears to be sex-specific and young mice with reduced PI3K signaling have increased risk of cardiac disease. Hence, it remains elusive as to whether PI3K inhibition is a valid strategy to delay aging and extend healthspan in humans. We recently demonstrated that reduced PI3K activity in cardiomyocytes delays cardiac growth, causing subnormal contractility and cardiopulmonary functional capacity, as well as increased risk of mortality at young age. In stark contrast, in aged mice, experimental attenuation of PI3K signaling reduced the age-dependent decline in cardiac function and extended maximal lifespan, suggesting (...)
A purinergic call to arms from dying brown adipocytes
Mohammed K. Hankir1
Brown adipocytes react to temperature and nutritional challenges by ramping up their metabolism and generating heat. This adaptation to changes in the environment is crucial for defending organismal homeostasis, but is impaired in obesity and during aging. Writing in Nature, Niemann et al. show that brown adipocytes become apoptotic under thermoneutral conditions and release ATP, which in turn is converted extracellularly into inosine. They further present evidence that pharmacological and genetic manipulations that enhance signalling of this purine metabolite stimulates thermo-genesis in brown adipocytes and promotes metabolic health.
Spermidine supplementation in rare translation-associated disorders
Andreas Zimmermann1,2, Didac Carmona-Gutierrez1, and Frank Madeo1,2,3
Spermidine is a naturally occurring polyamine that is strongly involved in manifold cellular processes, for example, DNA, RNA and protein stabilization, cell growth, proliferation, autophagy, and aging. Importantly, spermidine has