The role of short chain fatty acid substrates in aerobic and glycolytic metabolism in primary cultures of renal proximal tubule cells |
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Authors: | Richard D Griner Michael D Aleo Rick G Schnellmann |
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Institution: | (1) Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, 30602 Athens, Georgia;(2) Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, 30602 Athens, Georgia;(3) Present address: Pfizer, Central Research Division, Eastern Point Road, 06340 Groton, CT |
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Abstract: | Summary This study examined the role of odd and even short-chain fatty acid substrates on aerobic and glycolytic metabolism in well-aerated
primary cultures of rabbit renal proximal tubule cells (RPTC). Increasing oxygen delivery to primary cultures of RPTC by shaking
the dishes (SHAKE) reduced total lactate levels and lactate dehydrogenase (LDH) activity and reduced net glucose consumption
compared to RPTC cultured under standard conditions (STILL). The addition of butyrate, valerate, heptanoate, or octanoate
to SHAKE RPTC produced variable effects on glycolytic metabolism. Although butyrate and heptanoate further reduced total lactate
levels and net glucose consumption during short-term culture (<24 h), no fatty acid tested further reduced total lactate levels,
net glucose consumption, or LDH activity during long-term culture (7 days). During the first 12 h of culture, maintenance
of aerobic metabolism in SHAKE RPTC was dependent on medium supplementation with fatty acid substrates (2 mM). However, by 24 h, SHAKE RPTC did not require fatty acid substrates to maintain levels of aerobic metabolism equivalent
to freshly isolated proximal tubules and greater than STILL RPTC. This suggests that SHAKE RPTC undergo adaptive changes between
12 and 24 h of culture, which give RPTC the ability to utilize other substrates for mitochondrial oxidation, therefore allowing
greater expression of mitochondrial oxidative potential in SHAKE RPTC than in STILL RPTC. |
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Keywords: | aerobic metabolism glycolytic metabolism fatty acids renal proximal tubule cells glucose consumption lactate oxygen consumption |
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