Novel Hyperplastic Expansion of White Adipose Tissue Underlies the Metabolically Healthy Obese Phenotype of Male LFABP Null Mice

TL;DR

Mice lacking LFABP become obese but stay metabolically healthy by expanding subcutaneous fat through increased adipocyte numbers rather than size.

Contribution

The study reveals a novel mechanism of healthy obesity through hyperplastic expansion of white adipose tissue in LFABP null mice.

Findings

LFABP−/− mice on HFD have double the fat mass but smaller adipocytes compared to wild-type mice.

Deletion of Lfabp alters pathways related to adipose expansion, including cholesterol biosynthesis and adipogenesis.

LFABP absence may enhance interorgan communication, promoting metabolically beneficial SAT expansion.

Abstract

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 the liver and small intestine but not in adipose tissues; thus, its ablation may promote interorgan crosstalk that drives the hyperplastic expansion of metabolically beneficial SAT, contributing to the healthy obese phenotype of the LFABP−/− mouse.

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