Characterization of metabolic phenotypes and distinctive genes in mice with low‐weight gain

Being overweight exacerbates various metabolic diseases, necessitating the identification of target molecules for obesity control. In the current study, we investigated common physiological features related to metabolism in mice with low weight gain: (1) G protein‐coupled receptor, family C, group 5, member B‐knockout; (2) gastric inhibitory polypeptide receptor‐knockout; and (3) Iroquois‐related homeobox 3‐knockout. Moreover, we explored genes involved in metabolism by analyzing differentially expressed genes (DEGs) between low‐weight gain mice and the respective wild‐type control mice. The common characteristics of the low‐weight gain mice were low inguinal white adipose tissue (iWAT) and liver weight despite similar food intake along with lower blood leptin levels and high energy expenditure. The DEGs of iWAT, epididymal (gonadal) WAT, brown adipose tissue, muscle, liver, hypothalamus, and hippocampus common to these low‐weight gain mice were designated as candidate genes associated with metabolism. One such gene tetraspanin 7 (Tspan7) from the iWAT was validated using knockout and overexpressing mouse models. Mice with low Tspan7 expression gained more weight, while those with high Tspan7 expression gained less weight, confirming the involvement of the Tspan7 gene in weight regulation. Collectively, these findings suggest that the candidate gene list generated in this study contains potential target molecules for obesity regulation. Further validation and additional data from low‐weight gain mice will aid in understanding the molecular mechanisms associated with obesity. To identify genes associated with obesity, differentially expressed genes were screened from the adipose tissue, muscle, liver, and brain of mice that are less prone to obesity (Gprc5b, Gipr, and Irx3‐knockouts). A candidate gene, Tspan7, found to be differentially expressed in the subcutaneous fat tissue, was validated using knockout and overexpressing mouse models, confirming its involvement in weight regulation. The candidate gene list generated in this study may contain potential target molecules for obesity regulation.