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 (<i>LFABP</i><sup>−/−</sup>) becomes obese upon high-fat diet (HFD) feeding but remains metabolically healthy. He...

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Main Authors: Anastasia Diolintzi, Yinxiu Zhou, Angelina Fomina, Yifei Sun, Seema Husain, Labros S. Sidossis, Susan K. Fried, Judith Storch
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/11/760
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Summary: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 (<i>LFABP</i><sup>−/−</sup>) becomes obese upon high-fat diet (HFD) feeding but remains metabolically healthy. Here, we find that the obese <i>LFABP</i><sup>−/−</sup> 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 <i>LFABP</i><sup>−/−</sup> 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 <i>LFABP</i><sup>−/−</sup>. Transcriptomic analysis of SAT revealed that <i>Lfabp</i> 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 <i>LFABP</i><sup>−/−</sup> mouse.
ISSN:2073-4409