Tissue-Specific Ablation of Liver Fatty Acid-Binding Protein Induces a Metabolically Healthy Obese Phenotype in Female Mice.

Background/objectives: Obesity is associated with numerous metabolic complications including insulin resistance, dyslipidemia, and a reduced capacity for physical activity. Whole-body ablation of liver fatty acid-binding protein (LFABP) in mice was shown to alleviate several of these metabolic complications; high fat (HF) fed LFABP knockout (LFABP ) mice developed higher fat mass than their wild-type (WT) counterparts but displayed a metabolically healthy obese (MHO) phenotype with normoglycemia, normoinsulinemia, and reduced hepatic steatosis compared with WT. LFABP is expressed in both liver and intestine, thus in the present study, LFABP conditional knockout (cKO) mice were generated to determine the contributions of LFABP specifically within the liver or the intestine to the whole body phenotype of the global knockout.

Gut Microbiota and Phenotypic Changes Induced by Ablation of Liver- and Intestinal-Type Fatty Acid-Binding Proteins.

Intestinal fatty acid-binding protein (IFABP; FABP2) and liver fatty acid-binding protein (LFABP; FABP1) are small intracellular lipid-binding proteins. Deficiency of either of these proteins in mice leads to differential changes in intestinal lipid transport and metabolism, and to markedly divergent changes in whole-body energy homeostasis. The gut microbiota has been reported to play a pivotal role in metabolic process in the host and can be affected by host genetic factors.

Mechanisms underlying reduced weight gain in intestinal fatty acid-binding protein (IFABP) null mice.

Intestinal-fatty acid binding protein (IFABP; FABP2) is a 15-kDa intracellular protein abundantly present in the cytosol of the small intestinal (SI) enterocyte. High-fat (HF) feeding of IFABP mice resulted in reduced weight gain and fat mass relative to wild-type (WT) mice. Here, we examined intestinal properties that may underlie the observed lean phenotype of high fat-fed IFABP mice.