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Lack of Galectin-3 Disturbs Gut–Adipose–Liver Axis in High-Fat-Diet Mice Model

Year: 2026
Type: article
Abstract: Background/Objectives: A high-fat diet (HFD) promotes hepatic steatosis, inflammation, and systemic metabolic imbalance. Notably, HFDs can affect the gut–liver axis and adipose tissue homeostasis. Galectin-3 (Gal-3) binds to β-galactosides and plays regulatory roles in the gut–liver axis, connecting metabolic stress with inflammation and tissue remodelling. The objective of this study was to investigate whether Gal-3 affects the gut–liver axis and adipose tissue biology after HFD supplementation. Methods: Six-week-old C57BL/6 mice were randomly divided into either wild-type (Lgals3+/+) or knockout (Lgals3−/−) groups. Both groups received an HFD orally for 12 weeks, along with their respective control groups. Physiological measurements and microscopic examination of the gut, liver, and fat tissue were conducted using optical microscopy. Results: The HFD induced obesity in Lgals3+/+ mice, but not in Lgals3−/− mice, which exhibited lower weight gain, food intake, daily energy intake, and energy efficiency than Lgals3+/+ mice. Moreover, Lgals3−/− HFD mice had hyperglycaemia and hyperinsulinemia. Histological analysis revealed hypertrophied adipose tissue in Lgals3+/+ HFD mice with abundant Gal-3+ crown-like structures, rarely observed in Lgals3−/− HFD mice. In the jejunum, Lgals3+/+ HFD mice showed a significant reduction in Gal-3 expression in intestinal epithelial cells, whereas inflammatory signals were increased in Lgals3−/− HFD mice. In the liver, Lgals3+/+ HFD mice showed significant steatosis and macrophages expressing Gal-3. In contrast, Lgals3−/− HFD mice showed pronounced hepatocyte ballooning, suggesting a more progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD). Conclusions: Together, these data suggest that Gal-3 protects the gut–liver axis and adipose tissue against cytotoxic effects caused by HFD.
Source: Biomedicines
Language: English
Subfield: Epidemiology
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W7163641061
FWCI: 4.307
Cites: 54
Cited by: 1
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