The role of adipose tissue and subsequent liver tissue hypoxia in obesity and early stage metabolic dysfunction associated steatotic liver disease.

Autor: Van Eyck A; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium. annelies.vaneyck@uantwerpen.be.; Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium. annelies.vaneyck@uantwerpen.be., Kwanten WJ; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.; Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium., Peleman C; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.; Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium., Makhout S; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium., Van Laere S; Center of Oncological Research (CORE), MIPRO, IPPON, University of Antwerp, Antwerp, Belgium., Van De Maele K; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.; Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium., Van Hoorenbeeck K; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.; Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium., De Man J; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium., De Winter BY; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.; Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium., Francque S; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.; Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium., Verhulst SL; Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.; Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium.
Jazyk: angličtina
Zdroj: International journal of obesity (2005) [Int J Obes (Lond)] 2024 Apr; Vol. 48 (4), pp. 512-522. Date of Electronic Publication: 2023 Dec 23.
DOI: 10.1038/s41366-023-01443-w
Abstrakt: Background: Obesity is linked to several health complication, including Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD). Adipose tissue hypoxia has been suggested as an important player in the pathophysiological mechanism leading to chronic inflammation in obesity, and in the progression of MASLD. The study aims to investigate the effect of progressive obesity on adipose and liver tissue hypoxia.
Methods: Male 8-week-old C57BL/6J mice were fed a high-fat high-fructose diet (HFHFD) or control diet (CD) for 4, 8, 12, 16 and 20 weeks. Serum ALT, AST and lipid levels were determined, and glucose and insulin tolerance testing was performed. Liver, gonadal and subcutaneous adipose tissue was assessed histologically. In vivo tissue pO 2 measurements were performed in gonadal adipose tissue and liver under anesthesia. A PCR array for hypoxia responsive genes was performed in liver and adipose tissue. The main findings in the liver were validated in another diet-induced MASLD mice model, the choline-deficient L-amino acid defined high-fat diet (CDAHFD).
Results: HFHFD feeding induced a progressive obesity, dyslipidaemia, insulin resistance and MASLD. In vivo pO 2 was decreased in gonadal adipose tissue after 8 weeks of HFHFD compared to CD, and decreased further until 20 weeks. Liver pO 2 was only significantly decreased after 16 and 20 weeks of HFHFD. Gene expression and histology confirmed the presence of hypoxia in liver and adipose tissue. Hypoxia could not be confirmed in mice fed a CDAHFD.
Conclusion: Diet-induced obesity in mice is associated with hypoxia in liver and adipose tissue. Adipose tissue hypoxia develops early in obesity, while liver hypoxia occurs later in the obesity development but still within the early stages of MASLD. Liver hypoxia could not be directly confirmed in a non-obese liver-only MASLD mice model, indicating that obesity-related processes such as adipose tissue hypoxia are important in the pathophysiology of obesity and MASLD.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: