Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

Abstract

The energy metabolism of the retina might comply with daily changes in energy demand and is impaired in diabetic retinopathy—one of the most common causes of blindness in Europe and the USA. The aim of this study was to investigate putative adaptation of energy metabolism in healthy and diabetic retina. Hence expression analysis of metabolic pathway genes was performed using quantitative polymerase chain reaction, semi-quantitative western blot and immunohistochemistry. Transcriptional profiling of key enzymes of energy metabolism identified transcripts of mitochondrial fatty acid β-oxidation enzymes, i.e. carnitine palmitoyltransferase-1α (Cpt-1α) and medium chain acyl-CoA dehydrogenase (Acadm) to display daily rhythms with peak values during daytime in preparations of the whole retina and microdissected photoreceptors. The cycling of both enzymes persisted in constant darkness, was dampened in mice deficient for dopamine D4 (D4) receptors and was altered in db/db mice—a model of diabetic retinopathy. The data of the present study are consistent with circadian clock-dependent and dopaminergic regulation of fatty acid oxidation in retina and its putative disturbance in diabetic retina.

Shared and distinct lipid-lipid interactions in plasma and affected tissues in a diabetic mouse model

“…Therefore, it is likely that oxidized FFAs in the diabetic nerve are ultimately used for lipid synthesis via citrate. As a neural tissue, the retina is thought to be obligated to glucose metabolism, but the expression of proteins involved in lipid transport and -oxidation have been identified in human and rodent retinas (42)(43)(44)(45) and the retina has recently been shown to be capable of oxidizing palmitate (21,46). Thus, lowering of retinal lipids in diabetes could be due to either decreased transport or increased oxidation.…”

Qishen granules exerts cardioprotective effects on rats with heart failure via regulating fatty acid and glucose metabolism

“…Furthermore, CPT1, which facilitates the transportation of long chain FA into the mitochondrial matrix [34], was also increased by treatment of QSG. ACADL, ACADM, ACAA2 and SCP2, the critical enzymes for β-oxidation of FA within the mitochondria [26][27][28]35], were all upregulated by QSG treatment, indicating that QSG could promote fatty acid β-oxidation.…”

“…FAT/ CD36 medicates the entry of long-chain FA into cardiac cells [25], and CPT1 is the rate-limiting enzyme for transportation of FA from cytoplasm to mitochondria [9]. ACADL, ACADM, ACAA2 and SCP2 facilitate the metabolism of FA through β-oxidation in mitochondria [26][27][28]. The protein levels of cardiac FAT/CD36, CPT1A, ACADL, ACADM, ACAA2 and SCP2 were all impressively reduced in the model group compared to the sham group (P < 0.05 or P < 0.01, Fig.…”

Tributyrin Inhibits Ethanol-Induced Epigenetic Repression of CPT-1A and Attenuates Hepatic Steatosis and Injury

“…Up-regulation in hepatic CPT-1A expression occurs in response to hormones and nutrients whereas down-regulation in hepatic CPT-1A expression is observed under alcohol or high-fat feeding conditions as well as altered circadian rhythms affecting cellular metabolism. 12,[40][41][42] However, the molecular mechanisms, specifically epigenetic chromatin modifications that contribute to ethanol-induced changes in CPT-1A transcription, have not been completely elucidated. In the present study, we identified CPT-1A promoter-associated epigenetic mechanisms that underlie both physiologic and ethanol-mediated pathologic deregulation of CPT-1A gene expression.…”