Heart and skeletal muscle utilize long-chain fatty acids to provide a majority of their oxidative requirements. Studies of the regulation of HFABP expression have, therefore, focused on conditions under which mitochon-drial P-oxidation is modified.84 For instance, higher levels of HFABP are expressed in red gastrocnemius muscle than white, and expression increases following endurance training, both situations that parallel the relative mitochondrial P-oxidation levels.84 107 109 In a murine muscle cell line, HFABP content was increased in differentiated relative to undifferentiated cells, in parallel with the expression of creatine kinase activity and fatty acid P-oxidation.110
Little information is available about the regulation of HFABP expression by diet, and the available data are somewhat contradictory. Early studies by
Fournier and Rahim showed a 30% increase in heart HFABP levels following a high fat diet,111 whereas more recently others found no change in HFABP levels in rats fed diets ranging from 5 to 40% fat.84 It has also been reported that HFABP expression in mammary gland is increased upon feeding a high fat diet.112 In contrast to results for LFABP and IFABP, fasting was reported to result in an increase in the level of HFABP expression in heart, via an increase in gene transcription rate.113
The developmental expression of HFABP may also offer some insight into its potential for nutritional regulation. HFABP mRNA levels rise rapidly in rat heart 2 days prior to birth, and continue to rise during the high-fat diet suckling period. They reach a peak at the initiation of weaning, upon transition from the maternal high fat diet, and then decline slightly into adulthood. It was noted that these changes parallel those in cardiac mitochondrial P-oxi-dative capacity and mitochondrial abundance.114
A number of investigators have reported that heart HFABP levels increase during experimental diabetes mellitus.113,115,116 Although it would appear that the mechanism of this increase might be the same as that observed in starvation, the increase appears to be secondary to an increase in mRNA turnover time rather than to increased transcription rate.113 Unlike HFABP expression in the heart, HFABP expression in the aorta was found to be decreased in streptozotocin-diabetic rats, and this was reversed upon insulin treatment.117
The mechanism(s) of nutritional regulation of HFABP expression are unknown at present. Peroxisome proliferators have little or no effect on the levels of HFABP in heart and skeletal muscles, and little information is available about the promoter region of the HFABP gene.84,118 The existing literature supports the suggestion that the modulation of HFABP abundance is consistent with a role in fatty acid metabolism, particularly with the capacity of tissues to oxidize fatty acids for energy. The signals that affect this regulation remain to be revealed.
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