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Obesity’s Epigenetic ‘Memory’ Fuels Weight Regain
Developing
In Short: Researchers have discovered that obesity leaves a lasting 'memory' in fat cells, potentially explaining why weight regain is common after weight loss.
Senior author Atul Chopra, MD, PhD, from the Harrington Discovery Institute at University Hospitals and Case Western Reserve University, explained that obesity alters fat cells, keeping levels of the hunger hormone asprosin elevated.
Chopra noted, “We found that obesity leaves a lasting ‘memory’ in fat cells that keeps the hunger hormone asprosin turned on, even after weight is lost.”
The study, detailed in preclinical research, also found evidence that maternal obesity may produce changes in offspring before birth, increasing their susceptibility to obesity later in life.
Chopra said, “The biggest message is that weight regain is not a willpower problem but a biological one.”
The research identified an unexpected link between an obesity-associated cytokine and persistent chromatin remodeling at the Fbn1 locus, suggesting a potential shared mechanism underlying weight regain and transmission of obesity susceptibility to offspring.
Chopra added, “It’s like flipping a light switch that stays on after you remove your finger.”
The study sought to understand why people frequently regain weight after weight loss and why children of mothers with obesity have an increased susceptibility to obesity.
Among adipose-derived endocrine factors, asprosin has emerged as a potent hormonal signal elevated in obesity.
Four days of exposure to transforming growth factor-beta-1 (TGF-beta-1), a cytokine elevated in obesity, increased Fbn1 expression and asprosin production in cultured fat cells.
Chopra emphasized, “Even after the original trigger is gone, fat cells keep producing extra asprosin, which drives hunger and pushes the body to regain lost weight.”
For clinicians, Chopra said the findings supported treating obesity as an ongoing condition rather than considering treatment complete once a patient loses weight.
If the findings are replicated in humans, they could “open the door to a treatment that could be paired with weight-loss drugs to help people keep weight off after they stop taking them, or potentially to protect children of mothers with obesity before they’re even born,” Chopra said.
What this adds
The study highlights the biological mechanisms behind weight regain and obesity susceptibility in offspring, providing insights into potential future treatments.
What's still developing
- Relapse and inheritance could indicate that obesity leaves behind a molecular imprint that promotes its recurrence, the authors wrote.
- “We suspected that these two puzzles might have the same underlying answer,” Chopra said.
- “This is animal research, and the next step is confirming that the same ‘switch’ exists in human fat tissue and that it behaves the same way during human pregnancy,” Chopra said.
Sources
- Medscapelink