# The alteration of LBX1 expression is associated with changes in parameters related to energy metabolism in mice

## TL;DR

This study shows that changes in the LBX1 gene affect energy metabolism in mice, leading to lean body mass and resistance to obesity.

## Contribution

The study identifies LBX1 as a negative regulator of energy metabolism and links its dysfunction to lean body mass in a disease context.

## Key findings

- Mice lacking LBX1 in skeletal muscle are more resistant to high-fat diet-induced obesity.
- LBX1 loss improves glucose tolerance and increases maximal aerobic capacity in mice.
- Overexpression of LBX1 decreases glucose uptake in cultured cells.

## Abstract

The LBX1 gene is located near a single nucleotide polymorphism that is highly associated with susceptibility to adolescent idiopathic scoliosis and is considered one of the strongest candidate genes involved in the pathogenesis of this condition. We have previously found that loss of LBX1 from skeletal muscle results not only in spinal deformity but also in lean body mass, suggesting a potential role for LBX1 in energy metabolism. The purpose of the present study was to test this hypothesis by analyzing the phenotype of mice lacking LBX1 in skeletal muscle with a focus on energy metabolism. We found that loss of LBX1 rendered mice more resistant to high-fat diet-induced obesity, despite comparable food intake between mutant and control mice. Notably, the mutant mice exhibited improved glucose tolerance, increased maximal aerobic capacity, and higher core body temperature compared to control mice. In addition, we found that overexpression of LBX1 decreased glucose uptake in cultured cells. Taken together, our data show that LBX1 functions as a negative regulator of energy metabolism and that loss of LBX1 from skeletal muscle increases systemic energy expenditure resulting in lean body mass. The present study thus suggests a potential association between LBX1 dysfunction and lean body mass in patients with adolescent idiopathic scoliosis.