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Increased Endurance Exercise Capacity Secondary to Liver Fatty Acid‐Binding Protein Ablation
Author(s) -
Xu Heli,
Gajda Angela,
Zhou Yin Xiu,
Fatima Anam,
Agellon Luis B.,
Storch Judith
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1132.8
Subject(s) - fatty acid binding protein , mitochondrial biogenesis , endocrinology , medicine , biology , skeletal muscle , ampk , mitochondrion , biochemistry , enzyme , gene , protein kinase a
Two fatty acid‐binding proteins (FABPs) are abundantly expressed in proximal enterocytes, intestinal FABP (IFABP, FABP2) and liver FABP (LFABP, FABP2), both with high affinity for binding long chain fatty acids. We previously showed that LFABP and IFABP knockout mice have divergent phenotypes in response to high‐fat feeding, with LFABP −/− mice gaining more weight and body fat, and IFABP −/− mice remaining lean relative to wildtype (WT) mice. Interestingly, despite their obese phenotype, LFABP −/− mice showed signs of being metabolically healthy, with a similar glucose tolerance to WT mice regardless of their markedly greater fat mass and an increased endurance exercise performance. To explore this surprising exercise phenotype, here we focused on possible metabolic alterations in the skeletal muscle secondary to LFABP ablation. The results showed higher mitochondrial enzyme activities in LFABP −/− mouse muscle, along with an increased triglyceride level and decreased AMPK activity, indicating that the mice have abundant energy availability at rest, compared with WT mice. Upregulation of PGC1α and PPARα mRNA levels was also found, suggesting an induction of mitochondrial biogenesis and an adjustment in lipid utilization. These results suggest that although LFABP is not normally expressed in muscle, its ablation in liver and intestine appears to contribute to a higher mitochondrial content and efficiency in energy utilization in the skeletal muscle, leading to the higher endurance exercise capacity in the LFABP −/− mice. Support or Funding Information This work was supported by National Institutes of Health Grant DK‐38389 from NIDDK, and by funds from the New Jersey Agricultural Experiment Station (to J. S.).