Background: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a common metabolic liver condition primarily managed through lifestyle modification. Obeticholic acid (OCA), a farnesoid X receptor agonist, has shown therapeutic benefits in steatohepatitis, yet its short‐term metabolic effects remain unclear. This study compared OCA plus lifestyle modification versus lifestyle intervention alone in adults with MASLD. Methods: This quasi‐experimental study included 360 adults aged 18–60 years with ultrasound‐diagnosed MASLD and insulin resistance (HOMA − IR > 2.0). Patients with diabetes mellitus, viral hepatitis, cirrhosis, advanced fibrosis, ischemic heart disease or LDL − C > 160 mg/dL were excluded. Participants received either OCA (10 mg/day) plus standardised lifestyle modification or lifestyle intervention alone for 3 months. Anthropometric, biochemical and hepatic parameters were evaluated at baseline and follow‐up, with ANCOVA performed to adjust for baseline covariates. Results: Baseline demographic and metabolic characteristics were comparable between groups. After 3 months, the OCA plus lifestyle group demonstrated significantly greater improvements in ALT (36.65 ± 20.57 vs. 48.19 ± 21.35 U/L; p < 0.001), fatty liver index (55.99 ± 12.60 vs. 63.08 ± 11.89; p < 0.001) and HEPAMET score (0.33 ± 0.13 vs. 0.41 ± 0.13; p < 0.001), along with a greater reduction in body weight (77.28 ± 12.07 kg vs. 80.19 ± 12.37 kg; p = 0.024). Postintervention HOMA‐IR was significantly lower with OCA plus lifestyle than lifestyle alone (2.46 ± 0.92 vs. 2.96 ± 1.06; mean difference 0.50; p < 0.001). LDL‐C increased significantly in the OCA group (139.50 ± 15.74 mg/dL vs. 131.96 ± 16.36 mg/dL; p < 0.001). Conclusion: Over 3 months, OCA combined with lifestyle modification improved liver enzymes, steatosis and fibrosis‐related surrogate indices, and modestly reduced insulin resistance. Careful lipid monitoring is recommended, and longer term studies are required to clarify the overall metabolic and cardiovascular implications.

The global escalation in chronic obesity and its associated comorbidities has emerged as a substantial public health and economic challenge. This crisis is further compounded by the genomic impact of obesity on telomere length (TL), primarily driven by unchecked oxidative stress. As a result, telomeres shorten, leading to the onset of age-related disorders. In response, effective therapeutic interventions, notably bariatric surgery (BS), have demonstrated significant improvements in patient outcomes by reducing morbidity and mortality rates. Contemporary research has expanded on these benefits, investigating the impact of weight reduction on TL. While the majority of studies support the attenuation of telomeric attrition, ongoing debates surrounding methodological limitations and conflicting results underscore the need for further investigation. This narrative review outlines the current research on the mechanisms that influence telomeres, with a focus on the methodologies used to measure TL. Furthermore, we will examine the most recent findings on the effects of weight loss resulting from surgical intervention on telomere biology. This analysis aims to address specific controversies surrounding this topic and provide evidence-based recommendations valuable to the healthcare sector for mitigating obesity, as well as educating patients about the molecular-level effects of weight reduction resulting from surgical procedures, to enable informed consent.