Heterozygous GAA knockout is nonconsequential on metabolism and the spatial liver transcriptome in high-fat diet induced obese and prediabetic mice

The liver is composed of periportal and perivenous hepatocytes that have different metabolic profiles. This study used spatial transcritpomics to identify how high-fat diet induced obesity and heterozygous GAA knockout impacted the periportal and perivenous transcriptome. The spatial transcriptomics analysis revealed that heterozygous GAA knockout had no impact on liver transcriptomes. However, the high-fat diet, compared to the low-fat diet, reduced metabolic pathway gene abundance in both zones, while uniquely reducing ribosome gene abundance in perivenous hepatocytes. Four groups of mice were included in the analysis including 1) wildtype low-fat fed mice, 2) heterozygous GAA knockout low-fat diet fed mice, 3) wildtype high-fat diet fed mice, and 4) heterozygous GAA knockout high-fat diet fed mice. Formalin fixed paraffin embedded liver sections were used for the spatial transcriptomics analysis.