FABP4 reversed the regulation of leptin on mitochondrial fatty acid oxidation in mice adipocytes.

Abstract

Fatty acid binding protein 4 (FABP4), plays key role in fatty acid transportation and oxidation, and increases with leptin synergistically during adipose inflammation process. However, the regulation mechanism between FABP4 and leptin on mitochondrial fatty acid oxidation remains unclear. In this study, we found that FABP4 reduced the expression of leptin, CPT-1 and AOX1 in mice adipocytes. Conversely, FABP4 was down-regulated in a time-dependent manner by leptin treatment. Additionally, forced expression of FABP4 attenuated the expression of PGC1-α, UCP2, CPT-1, AOX1 and COX2 compared with leptin incubation. Moreover, mitochondrial membrane potential, fatty acid oxidation enzyme medium-chain acyl-CoA dehydrogenase (MCAD), long-chain acyl-CoA dehydrogenase (LCAD) and Cyt C levels were reduced in response to the overexpression of FABP4. These reductions correspond well with the reduced release of free fatty acid and the inactivation of mitochondrial complexes I and III by FABP4 overexpression. Furthermore, addition of the Akt/mTOR pathway-specific inhibitor (MK2206) blocked the mitochondrial fatty acid oxidation and respiration factors, whereas interference of FABP4 overcame these effects. Taken together, FABP4 could reverse the activation of the leptin-induced mitochondrial fatty acid oxidation, and the inhibition of Akt/mTOR signal pathway played a key role in this process.

• Authors: Lu Gan, Zhenjiang Liu, Weina Cao, Zhenzhen Zhang, Chao Sun
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 13588 (Aug 27 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26310911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fabp4 protein, mouse
• Fatty Acid-Binding Proteins
• Fatty Acids
• Leptin
• Oligomycins
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Adipocytes (drug effects, metabolism)
• Animals
• Cell Respiration (drug effects)
• Fatty Acid-Binding Proteins (metabolism)
• Fatty Acids (metabolism)
• Gene Expression Regulation (drug effects)
• Leptin (metabolism)
• Male
• Membrane Potentials (drug effects)
• Mice
• Mitochondria (metabolism)
• Models, Biological
• Oligomycins (pharmacology)
• Oxidation-Reduction (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)