Lactate utilization in Lace1 knockout mice promotes browning of inguinal white adipose tissue

Abstract

Recent studies have focused on identifying novel genes involved in the browning process of inguinal white adipose tissue (iWAT). In this context, we propose that the mitochondrial ATPase gene lactation elevated 1 (Lace1) utilizes lactate to regulate the browning capacity of iWAT, specifically in response to challenge with CL-316,243 (CL), a beta3-adrenergic receptor (β3-AR) agonist. The mice were injected with CL over a span of 3 days and exposed to cold temperatures (4–6 °C) for 1 week. The results revealed a significant increase in Lace1 expression levels during beige adipogenesis. Additionally, a strong positive correlation was observed between Lace1 and Ucp1 mRNA expression in iWAT under browning stimulation. To further explore this phenomenon, we subjected engineered Lace1 KO mice to CL and cold challenges to validate their browning potential. Surprisingly, Lace1 KO mice presented increased oxygen consumption and heat generation upon CL challenge and cold exposure, along with increased expression of genes related to brown adipogenesis. Notably, deletion of Lace1 led to increased lactate uptake and browning in iWAT under CL challenge compared with those of the controls. These unique phenomena stem from increased lactate release due to the inactivation of pyruvate dehydrogenase (PDH) in the hearts of Lace1 KO mice. In recent years, researchers have found that certain conditions can change white fat cells into beige fat cells, a process called “browning.” In this study, scientists focused on finding new genes that help in the browning of white fat cells. They did this by treating mice with a compound that starts the browning process and studying changes in gene activity. They found that the Lace1 gene is very active in brown fat tissue and its activity increases during the browning of white fat. The main discovery of this research is that not having the Lace1 gene leads to browning of white fat tissue in mice, suggesting that Lace1 may slow down this process. The researchers conclude targeting the Lace1 gene could be a new way to promote the browning of white fat and fight obesity. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.