Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes

Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Duncan Building, Liverpool L69 3GA, UK.
Pflügers Archiv - European Journal of Physiology (Impact Factor: 3.07). 10/2009; 459(3):509-18. DOI: 10.1007/s00424-009-0750-3
Source: PubMed

ABSTRACT Hypoxia modulates white adipose tissue function, and this includes stimulating glucose uptake and the expression of facilitative glucose transporters (particularly GLUT1) in adipocytes. This study has examined the effect of hypoxia on lactate release from adipocytes and whether the monocarboxylate transporters that mediate lactate transport (MCTs1-4) are expressed in human adipocytes and are induced by low O(2) tension. Exposure of human Simpson-Golabi-Behmel syndrome adipocytes to 1% O(2) for 24 h resulted in increased lactate release (2.3-fold) compared with cells in normoxia (21% O(2)). Screening by reverse transcription polymerase chain reaction indicated that the genes encoding MCT1, MCT2, and MCT4 are expressed in human adipose tissue, and in adipocytes and preadipocytes in culture. Hypoxia (48 h) increased MCT1 (8.5-fold) and MCT4 (14.3-fold) messenger RNA (mRNA) levels in human adipocytes, but decreased MCT2 mRNA (fourfold). MCT1 protein level was also increased (2.7-fold at 48 h) by hypoxia, but there was no change in MCT4 protein. The changes in MCT gene expression induced by hypoxia were reversed on return to normoxia. Treatment with the hypoxia mimetic CoCl(2) resulted in up-regulation of MCT1 (up to twofold) and MCT4 (fivefold) mRNA level, but there was no significant effect on MCT2 expression. It is concluded that hypoxia increases lactate release from adipocytes and modulates MCT expression in a type-specific manner, with MCT1 and MCT4 expression being hypoxia-inducible transcription factor-1 (HIF-1) dependent. Increased lactate production and monocarboxylate transporter expression are likely to be key components of the adaptive response of adipocytes to low O(2) tension as adipose tissue mass expands in obesity.

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