Fat Cells May Keep an “Obesity Memory” That Promotes Weight Regain
Researchers identified a biological pathway that may explain why the body remains prone to regaining weight after obesity. In mice, obesity caused lasting changes in fat cells that kept asprosin, an appetite-stimulating hormone, elevated even after weight loss, with TGF-β1 appearing to trigger epigenetic alterations. Human dataset evidence supported the mechanism, though direct confirmation in people is still needed, and the same signal may pass from mother to child and increase obesity susceptibility.
Researchers at Harrington Discovery Institute and Case Western Reserve found in mice that obesity changes fat cells so asprosin, a hormone that boosts appetite, remains high after weight loss. TGF-β1 appears to trigger an epigenetic shift that lasts for weeks, even when TGF-β1 returns to normal.
Public human datasets supported this mechanism, but direct human confirmation is still needed. The same signal may cross the placenta, potentially giving newborns a predisposition toward obesity. The work appears in Cell Reports.
If confirmed in people, this mechanism could reshape how patients, clinicians, and families understand weight regain after obesity treatment. People stopping GLP-1 drugs may face renewed hunger driven by lingering cellular changes, not simply lapses in behavior. Mothers with obesity may pass heightened risk to children, potentially influencing prevention efforts. It may also reduce stigma by framing relapse as biological, while underscoring the need for long-term strategies.