Obesity, Not Liver Fat, Drives Link Between Depression and Fatty Liver Disease: UK Biobank Study

Using data from the UK Biobank, the study included over 36,500 participants with a mean age of 64.5 years, of whom more than half were female. Liver fat was assessed using magnetic resonance imaging (MRI)-derived proton density fat fraction, and SLD was defined as liver fat content equal to or above 5%. Depression was determined based on self-reported diagnoses and hospital records.

The study revealed the following findings:

• In the cross-sectional analysis, individuals with steatotic liver disease (SLD) had a higher prevalence of depression compared to those without SLD (9.1% vs 7.3%).
• After adjusting for age, sex, and socioeconomic status, SLD was associated with a 40% higher odds of depression.
• This association reduced significantly to a 12% increase in odds after accounting for body mass index (BMI), suggesting obesity may be a key confounding factor.
• In the prospective analysis involving over 33,700 individuals followed for a median of 4.5 years, 414 new cases of depression were identified.
• Initially, SLD was linked to a 27% increased risk of developing depression.
• After adjusting for BMI, this association was no longer statistically significant.
• Incremental increases in liver fat (per 5%) were not linked to future risk of depression.
• The study found no significant differences in these associations between men and women.

“These findings carry significant implications for clinical care and public health,” the authors noted. The data suggests that targeting obesity through lifestyle changes or weight reduction strategies may be a more effective approach to reducing depression risk in individuals with fatty liver disease, rather than focusing on liver fat alone.

The researchers emphasized that while liver fat and depression appear connected, the relationship may be driven by reverse causation and shared risk factors such as obesity. They called for future investigations into how weight management and other lifestyle interventions could impact both metabolic and mental health outcomes.

The authors concluded, "While SLD is associated with an increased likelihood of depression, the link seems to be largely explained by excess weight. The study highlights obesity as a critical modifiable factor in the interplay between liver health and mental well-being, highlighting the importance of holistic care strategies that address both physical and psychological health."

Reference:

Feng Q, Izzi-Engbeaya CN, Manousou P, Woodward M. Obesity drives the link between liver fat and depression: Cross-sectional and prospective investigations. Diabetes Obes Metab. 2025 Jun 24. doi: 10.1111/dom.16562. Epub ahead of print. PMID: 40555708.