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“Hepatic HKDC1 Deletion Alleviates Western Diet-Induced MASH in Mice” investigates the role of hexokinase domain containing 1 (HKDC1) in the development of metabolic dysfunction-associated steatohepatitis (MASH) induced by a Western diet in mice. The study demonstrates that deletion of HKDC1 in hepatic tissues leads to a significant reduction in liver inflammation, steatosis, and fibrosis associated with MASH i.e reduced pro-inflammatory and pro-fibrotic gene expression, while gut microbiome analysis indicated a shift toward MASH-protective bacteria. This research contributes to the field by elucidating a potential therapeutic target for treating metabolic liver diseases, particularly those exacerbated by dietary factors. By focusing on HKDC1, the authors provide insights into metabolic pathways that could be manipulated to mitigate liver damage and improve overall metabolic health.

Major issues

• Additional study may be required to validate these findings in larger animal models or clinical trials involving human subjects.

• There is lack of exploration into the underlying mechanisms by which HKDC1 deletion exerts its protective effects against MASH. A more detailed investigation into signaling pathways and metabolic changes resulting from HKDC1 loss will strengthen the conclusions drawn from this study.

Minor issues

• Some figures could benefit from clearer labeling and legends to enhance understanding for readers unfamiliar with specific methodologies used.

• Authors provide more context on how dietary components specifically influence HKDC1 expression will improve flow and coherence within the manuscript.

• The discussion section will be more enhanced by including more references to existing literature on similar pathways involved in liver metabolism and disease progression.

Competing interests

The author declares that they have no competing interests.