Role of adipocyte ATF3 in metabolic disorders

lab animal Research highlights Metabolic disorders https://doi.org/10.1038/s41684-024-01487-z Role of adipocyte ATF3 in metabolic disorders Check for updates Obesity-related metabolic disorders, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), affect millions of individuals worldwide. Adipose tissue has a central role in metabolic health and exists as white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates heat. Although BAT levels decline substantially after adolescence, promoting the browning of WAT and activating BAT have emerged as promising strategies for managing obesity and related metabolic disorders. Activating transcription factor 3 (ATF3) is known for its anti-inflammatory functions and its role in converting WAT into a BAT-like phenotype. Hepatic ATF3 helps prevent MASH and is involved in lipid metabolism. However, the metabolic function of ATF3 in adipocytes remains unclear. In a study in Communications Biology, researchers explored the role of adipocyte ATF3 in obese mice. The study showed that, when compared to lean controls, ATF3 levels were significantly elevated in the adipocytes of both obese humans and mice. To study the role of ATF3, the team deleted ATF3 in the adipocytes of mice by crossbreeding floxed Atf3 (Atf3fl/fl) mice with adipoq-Cre mice. In adipocyte ATF3-deficient mice fed a Western diet, MASLD developed, and obesity markers such as body fat content and adipocyte size also increased compared to Atf3fl/fl mice. When comparing the effects of standard versus high-fat diets, metabolic dysfunction appeared in ATF3-deficient mice regardless of dietary fat content. The lack of ATF3 worsened obesity and MASLD independently of the AMPK pathway—initially suspected to be involved due to its role in glucose and fatty acid metabolism. Instead, ATF3 deficiency triggered a series of metabolic effects, enhancing lipolysis in WAT and leading to increased lipogenesis and inflammation in liver cells. These findings suggest that adipocyte ATF3 serves as an important regulator of metabolic balance, similar to hepatic ATF3’s role in preventing MASH, though through different mechanisms. Adipocyte ATF3 emerges as a promising target for future therapies aiming to treat MASH and related obesity-driven metabolic disorders. Jorge Ferreira Original reference: Hu, S. et al. Commun. Biol. 7, 1300 (2024) Scientific Reports is an open access journal publishing original research from across all areas of the natural and clinical sciences. As a leading multi-disciplinary open access journal with over 1.5 million readers a month, Scientific Reports is the perfect place to publish your research. • Expert Editorial Board to manage your paper • Follows Nature Portfolio’s high peer review standards • Indexed in Web of Science, PubMed and other major repositories • Research accessed from over 180 countries worldwide nature.com/scientificreports A116065 Lab Animal | Volume 53 | December 2024 | 359 359  (...truncated)