Finnish study provides insight about gene regulation in obesity
The study suggests that reduced mitochondrial metabolism can contribute to body fat accumulation and diminished insulin sensitivity which can, in turn, trigger chemical DNA modifications that alter gene regulation.
May 25, 2025
In obesity and its comorbidities, mitochondrial activity is often impaired, yet it has remained unclear whether this impairment increases the risk of obesity or whether obesity itself damages mitochondria.
“Obesity is a major and growing public-health challenge in Finland. Our findings add key insight into how declining mitochondrial metabolism contributes to obesity and likely sets up a vicious cycle that sustains excess weight and hinders weight loss,” says Miina Ollikainen, researchers at the University of Helsinki and the Minerva Foundation Institute for Medical Research and leader of the study.
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Finnish twins
The study, published in Nature Communications, has untangled these complex cause-and-effect relationships by studying nearly 90 Finnish twin pairs.
When the team compared mitochondrial quantity with changes in DNA methylation, a chemical modification that regulate gene activity, one gene involved in cell growth and nutrient sensing stood out. The more overweight a person was – and the fewer mitochondria detected in their adipose tissue – the more active the gene SH3BP4 was.
“Our data suggest that when mitochondrial metabolism falters, for example because of calorie surplus, a feedback loop promoting obesity is set in motion, which in turn may activate SH3BP4,” says first author and doctoral researcher Aino Heikkinen of the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM).
“I am glad to have contributed direct answers to human biology”
Kirsty Spalding started her career as a neuroscientist and given a succession of casual events, she ended up studying adipose biology.
Personalized obesity therapies
The scientists showed that especially reduced insulin sensitivity and an elevated body fat percentage – rather than weight gain alone – link both to mitochondrial quantity and to gene regulation.
Developing personalized obesity therapies requires an in-depth understanding of many intertwined mechanisms; this work marks a step toward that goal, the scientists state.
Updated: June 12, 2025, 06:35 am
Published: May 25, 2025
