Conclusions
This study identifies Crabp1's physiological role against the development of obesity. The protective function of CRABP1 is likely attributed to its classically proposed (canonical) activity as a trap for RA, which will reduce RA availability, thereby dampening RA-stimulated ERK1/2 activation and adipocyte hypertrophy. The results suggest Crabp1 as a potentially new therapeutic target in managing obesity and metabolic diseases.
Methods
In animal studies, 6 weeks old male wild type and CKO mice were fed with ND or high-fat diet (HFD) for 10 weeks. Body weight and food intake were regularly monitored. Glucose tolerance test and biological parameters of plasma (glucose and insulin levels) were measured after 10 weeks of ND vs. HFD feedings. Visceral adipose tissues were collected for histological and molecular analyses to determine affected signaling pathways. In cell culture studies, the 3T3L1 adipocyte differentiation model was used to examine and validate relevant signaling pathways.
Results
CKO mice, compared to WT mice, gained more body weight, exhibited more elevated fasting plasma glucose levels, and developed more severe impaired glucose tolerance under both ND and HFD. Histological examination revealed readily increased adipocyte hypertrophy and adipose tissue inflammation under HFD feedings. In 3T3L1 adipocytes, Crabp1 silencing enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, accompanied by elevated markers and signaling pathways of lipid accumulation and adipocyte hypertrophy. Conclusions: This study identifies Crabp1's physiological role against the development of obesity. The protective function of CRABP1 is likely attributed to its classically proposed (canonical) activity as a trap for RA, which will reduce RA availability, thereby dampening RA-stimulated ERK1/2 activation and adipocyte hypertrophy. The results suggest Crabp1 as a potentially new therapeutic target in managing obesity and metabolic diseases.