Obesity Drug Tirzepatide: Weight and Fatty Liver Improve, but Adipose Tissue Inflammation Persists

Research Team Led by MiHye Seo at Soonchunhyang University Seoul Hospital

Tirzepatide, which is increasingly being used as an obesity treatment, has been shown in animal studies to improve body weight, fatty liver, and blood glucose levels, but does not sufficiently reduce inflammation and fibrosis in adipose tissue.

MiHye Seo, Professor of Endocrinology and Metabolism at Soonchunhyang University Seoul Hospital

Soonchunhyang University Seoul Hospital announced on August 5 that a research team led by MiHye Seo, Professor in the Division of Endocrinology and Metabolism (including Professors Hyung Kyu Park and KyoiI Seo) published these findings in the online edition of the journal 'Endocrinology & Metabolism,' the official journal of the Korean Endocrine Society (title: 'Persistent Adipose Tissue Inflammation Despite Recovery of Metabolic Indicators: Tissue-Specific Immunoregulation of Tirzepatide').

Professor Seo's team, in collaboration with Professor Gyewon Jo's team at the Soonchunhyang Institute of Medi-bio Science (SIMS), administered tirzepatide to mice with obesity induced by a high-fat diet for 25 days. The researchers then precisely compared changes in inflammation and fibrosis in adipose tissue against those in hepatic tissue using tissue staining, gene expression analysis, and flow cytometry.

The results showed that the obese mice treated with tirzepatide experienced significant reductions in body weight and body fat mass, alongside increased energy expenditure. Hyperglycemia and impaired glucose tolerance also improved to normal levels, confirming anti-obesity and anti-diabetes effects. However, in adipose tissue, even after weight loss, features such as immune cell infiltration, collagen accumulation, and activation of fibrosis-related signaling pathways persisted.

These findings remained consistent even in follow-up experiments with severely obese mice, where body weight was reduced by more than 20 percent. In contrast, inflammation and fibrosis in hepatic tissue were clearly improved under the same conditions, indicating that different tissues can exhibit differential responses to the same medication.

The study found that hepatic macrophages responded to the drug with reduced inflammation, while macrophages residing in adipose tissue remained activated due to chronic metabolic stress and showed low drug responsiveness. The research team interpreted this difference as a factor contributing to the continued inflammation in adipose tissue.

Professor Seo stated, "Tirzepatide is effective in improving body weight and blood glucose, but this study confirmed that inflammation and fibrosis in adipose tissue cannot be fully resolved with weight loss alone." She added, "Additional research is needed to investigate what changes occur in tissue remodeling, including inflammation and fibrosis of adipose tissue, with long-term administration."

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