Liver Fatty Acid-Binding Protein (LFABP) Ablation Drives Hyperplastic Expansion of Subcutaneous Adipose Tissue in Male Mice Fed High-Fat Diet.

Liver fatty acid-binding protein (LFABP) functions both in intracellular lipid trafficking in liver and small intestine, and in systemic energy homeostasis regulation. We found that despite the marked obesity of high fat-fed LFABP null (LFABP ) mice compared to their wild-type (WT) counterparts, they display a 'metabolically healthy obese' (MHO) phenotype characterized by normoglycemia and normoinsulinemia, increased spontaneous physical activity, and a resistance to high-fat diet (HFD)-induced decline in exercise capacity. They also display increased muscle fatty acid oxidation suggesting that adipose tissue lipolysis is enhanced. To gain insight into the effects of Lfabp ablation on the quality of adipose tissue, we determined the mass and cellularity of the inguinal (iWAT) and epididymal (eWAT) white adipose tissues. LFABP mice fed HFD for 12 weeks weighed 23.7% more (BW, g: 41.7 LFABP vs 33.7 WT, p=0.006, n=5) and their fat pads tended to be heavier (iWAT, g: 1.1 LFABP vs 0.8 WT, p=0.060, n=5; eWAT, g: 1.4 LFABP vs 1.8 WT, p=0.065, n=5). Intriguingly, as shown in Figure 1, adipocyte size of iWAT adipocytes is smaller than that of the WT mice (44.6pL LFABP vs 188.1pL WT per cell, p=0.009, n=5). Adipocyte number was substantially increased in the iWAT of LFABP (23.6 LFABP vs 4.6 WT x 10 , p=0.001, n=5). In contrast, the eWAT adipocyte size in the LFABP is comparable to WT (210pL LFABP vs 268 pL WT per cell, p=0.293, n=5), and eWAT fat cell number was highly variable and trended higher in the LFABP mice (9.8 LFABP vs 4.7 WT x 10 , p=0.059, n=5). Because LFABP is not expressed in adipose tissue, our data suggest that its ablation promotes interorgan signaling that may limit hypertrophy and drive hyperplasia in expansion of potentially metabolically beneficial subcutaneous iWAT. More studies are warranted to elucidate the marked differences in cell size and the apparent depot-dependent effects of LFABP deficiency, as well as the mechanisms by which it modulates adipocyte growth and function.