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We previously showed that the liver fatty acid-binding protein null mouse (LFABP\u2212\/\u2212) becomes obese upon high-fat diet (HFD) feeding but remains metabolically healthy. Here, we find that the obese LFABP\u2212\/\u2212 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\u2212\/\u2212 mice had almost double the fat mass of WT, SAT adipocyte size was &gt;4-fold smaller and adipocyte number was 5-fold higher in the LFABP\u2212\/\u2212. 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\u2212\/\u2212 mouse.<\/jats:p>","DOI":"10.3390\/cells14110760","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T08:49:57Z","timestamp":1747903797000},"page":"760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Hyperplastic Expansion of White Adipose Tissue Underlies the Metabolically Healthy Obese Phenotype of Male LFABP Null Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9146-1093","authenticated-orcid":false,"given":"Anastasia","family":"Diolintzi","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ 08901, USA"},{"name":"Rutgers Center for Lipid Research, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinxiu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Fomina","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Sun","sequence":"additional","affiliation":[{"name":"The Mount Sinai Center for RNA Biology and Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Husain","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"},{"name":"BioReference Laboratories Inc., Elmwood Park, NJ 07407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Labros S.","family":"Sidossis","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ 08901, USA"},{"name":"Rutgers Center for Lipid Research, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"Fried","sequence":"additional","affiliation":[{"name":"Diabetes, Obesity & Metabolism Institute (DOMI), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5482-1777","authenticated-orcid":false,"given":"Judith","family":"Storch","sequence":"additional","affiliation":[{"name":"Rutgers Center for Lipid Research, New Brunswick, NJ 08901, USA"},{"name":"Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.plefa.2014.10.001","article-title":"Enterocyte fatty acid-binding proteins (fabps): Different functions of liver and intestinal fabps in the intestine","volume":"93","author":"Gajda","year":"2015","journal-title":"Prostaglandins Leukot. 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