Loss of the p38 MAPK-activated protein kinase MK2 does not significantly alter the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) in mice on high-fat/high-sugar diet (HFSD)

Background MK2 is a direct target of the stress-activated MAPK p38 and regulates inflammatory processes. MK2-deficient mice are protected in inflammatory disease models, which confirmed the kinase as interesting therapeutic target. Since MASLD is associated with low grade chronic inflammation, we analyzed the progression of the disease in MK2-deficient mice.

Methods Wildtype and MK2-deficient mice were fed a HFSD for 16 or 24 weeks. Body, liver, epididymal fat weight and non-fasted blood glucose levels were documented. TD-NMR analysis determined lean/fat mass as well as free body fluid. Liver steatosis, inflammation, potential fibrosis, and alterations of the adipose tissue were analyzed by immunohistochemistry. Expression of metabolic and inflammatory markers were monitored by qPCR analyses of liver and fat tissue.

Results MK2-deficient mice were significantly lighter than wildtype mice after 16 and 24 weeks of HFSD, mainly due to less lean mass and free body fluid rather than fat mass. Accordingly, liver weight, epididymal fat mass and blood glucose levels were not significantly altered. No significant difference in adipocyte size, crown-like structures or the expression of inflammation markers was detectable in adipose tissue. Similarly, quantification of the Sudan IV-positive lipid rich area in the liver and qPCR analysis of metabolic and inflammatory markers in liver tissue did not display significant alterations between wildtype and MK2-deficient mice.

Conclusion Despite its known function in the regulation of inflammation, the loss of MK2 expression does not significantly alter the progression of MASLD in mice after 16 or 24 weeks of HFSD.

Publication History

Article published online:
23 January 2024