Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity1,2. However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes3,4. Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss. Furthermore, we find persistent obesity-induced alterations in the epigenome of mouse adipocytes that negatively affect their function and response to metabolic stimuli. Mice carrying this obesogenic memory show accelerated rebound weight gain, and the epigenetic memory can explain future transcriptional deregulation in adipocytes in response to further high-fat diet feeding. In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic 'yo-yo' effect often seen with dieting. Targeting these changes in the future could improve long-term weight management and health outcomes.
Achieving net zero global emissions of carbon dioxide (CO2), with declining emissions of other greenhouse gases, is widely expected to halt global warming. CO2 emissions will continue to drive warming until fully balanced by active anthropogenic CO2 removals. For practical reasons, however, many greenhouse gas accounting systems allow some "passive" CO2 uptake, such as enhanced vegetation growth due to CO2 fertilisation, to be included as removals in the definition of net anthropogenic emissions. By including passive CO2 uptake, nominal net zero emissions would not halt global warming, undermining the Paris Agreement. Here we discuss measures addressing this problem, to ensure residual fossil fuel use does not cause further global warming: land management categories should be disaggregated in emissions reporting and targets to better separate the role of passive CO2 uptake; where possible, claimed removals should be additional to passive uptake; and targets should acknowledge the need for Geological Net Zero, meaning one tonne of CO2 permanently restored to the solid Earth for every tonne still generated from fossil sources. We also argue that scientific understanding of net zero provides a basis for allocating responsibility for the protection of passive carbon sinks during and after the transition to Geological Net Zero.
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