Novel hyperplastic expansion of white adipose tissue underlies the metabolically healthy obese phenotype of male LFABP null mice

Obesity is an important risk factor for the development of metabolic syndrome disorders. We previously showed that the liver fatty acid-binding protein null mouse (LFABP ^−/− ) becomes obese upon high-fat diet (HFD) feeding but remains metabolically healthy. Here we find that the obese LFABP ^−/− mouse increases subcutaneous adipose tissue (SAT) mass by markedly increasing the number rather than the size of adipocytes, as is typical with HFD. Indeed, while HFD-fed LFABP ^−/− mice had almost double the fat mass of WT, SAT adipocyte size was >4-fold smaller and adipocyte number was 5-fold higher in the LFABP ^−/− . Transcriptomic analysis of SAT revealed that Lfabp deletion alters the expression of multiple pathways that modulate adipose expansion and function including cholesterol biosynthesis, adipogenesis, and extracellular matrix remodeling. LFABP is expressed in liver and small intestine but not in adipose tissues, thus its ablation may promote interorgan crosstalk that drives hyperplastic expansion of metabolically beneficial SAT, contributing to the healthy obese phenotype of the LFABP ^−/− mouse.