Work

Oct-B: A derivative of L-BAIBA significantly alleviating high-fat diet-induced obesity in mice

Year: 2024

Type: article

Abstract: The rising prevalence of obesity is a global health concern. Supplementation with ( S )-β-aminoisobutyric acid ( L -BAIBA) has shown potential in preventing obesity and related metabolic disorders induced by high-fat diets. However, developing effective and low-toxicity BAIBA derivatives remains a challenging yet promising field. In this study, we introduce Oct-B , a novel BAIBA ester compound, which exhibits 80-fold greater efficacy than L -BAIBA in alleviating obesity in high-fat diet-fed mice. Our results demonstrate that Oct-B significantly reduces serum TG, TC, LDL-C, and the activities of ALT and AST, and also reduces TG and TC in liver, surpassing the effects of L -BAIBA. Histological analysis shows that Oct-B significantly decreases lipid accumulation in liver tissues, normalizes mast cells in white adipose tissue, and upregulates the expression of UCP1 protein in white adipose tissue. The qRT-PCR results indicated Oct-B alleviates obesity by downregulating lipogenic genes (PPARγ, ACC1, FAS), upregulating lipolysis related genes (PPARα, HSL) and thermogenic gene UCP1. Additionally, quantitative mass spectrometry reveals a marked increase in L -BAIBA levels in white fat, brown fat, serum, and muscle following Oct-B administration. These findings suggest that Oct-B is an efficient L -BAIBA substitute, offering a promising therapeutic approach for preventing and treating high-fat diet-induced obesity. • Oct-B, a BAIBA ester, increase L -BAIBA levels in tissues of obese mice. • Oct-B shows 80x greater efficacy than L -BAIBA in reducing obesity. • Oct-B reduces lipid accumulation, upregulates UCP1 in adipose tissue. • Oct-B modulates lipogenic, lipolysis, & thermogenic genes.

Source: Biochemical and Biophysical Research Communications

DOI: 10.1016/j.bbrc.2024.150739