Intracellular FABPs

It has been known for some time that the expression of LFABP was increased by a seemingly heterogeneous group of compounds that caused the proliferation of peroxisomes,124,135-138 and that induction of hepatic peroxisomal P-oxidation capacity correlates strongly with the increase in LFABP levels.139 Indeed, when ethanol, which impairs mitochondrial P-oxidation and stimulates peroxisomal P-oxidation, was added to a high fat diet, LFABP was found to be expressed at levels up to 20% of soluble protein.140 Dicarboxylic acids, FA metabolites that are found under conditions of impaired mitochondrial P-oxidation or with high levels of FA flux, have also been shown to increase LFABP mRNA levels in cultured hepato-cytes.135,141 It is now known that these compounds, which include long-chain FA, bind to and activate PPARs. In mice null for PPARa, fasting induced a fatty liver accompanied by severe impairment of fatty acid oxidation, and LFABP expression was dramatically decreased in the the PPARa-/- fasted rats.142 The relationship between LFABP expression and peroxisome proliferation is not absolute, however, as normal LFABP levels are present in infants with Zellweger's syndrome, who have a complete absence of peroxisomal biogenesis.73 Thus, LFABP expression appears to be coordinated with, but not dependent on, peroxisomal oxidative capacity.

Studies in cultured cell lin es are consistent with PPRE-mediated regulation of LFABP expression. Besnard and colleagues demonstrated that long-chain FA increases the transcription rate of the LFABP gene in rat hepatoma cells, and that 9-cis-retionoic acid enhances this induction.143-145 Increased LFABP synthesis following incubation with linoleic acid was also reported,146 although others have found that oleate was effective only under conditions where P-oxidation was inhibited.135,141

It is likely that the effects of long-chain fatty acids on AFABP expression are also mediated via interactions with PPAR transcription factors. PPARy was shown to bind the arachidonate metabolite 15-deoxy A12,14 prostaglandin J2,147,136 forming a heterodimer with RXRa and thereby activating

AFABP transcription.148 Indeed, both LFABP and AFABP contain functional PPRE homolog sequences in the promoter region of their genes (Table 6.2) and are upregulated by PPARa and PPARy, respectively.137141148 Antidia-betic agents such as the thiazolidinediones increase AFABP mRNA levels presumably by increasing insulin sensitivity, and appear to be operating via the same mechanism of activation of nuclear hormone receptors as do long-chain fatty acids.119

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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