Regulation of lactate metabolism in vivo

Buchalter, Scott E.; Crain, Michael R.; Kreisberg, Robert A.

doi:10.1002/dmr.5610050405

Cited by 67 publications

(34 citation statements)

References 76 publications

(5 reference statements)

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“…Another major substrate of the basolateral MCT1, as described by Garcia et al (9), may be lactate. Since the intestinal epithelium converts large amounts of glucose to lactate after a carbohydrate-rich meal, it must expel the lactate to avoid intracellular acidosis (1). These data totally support the idea that MCT1 functions mainly in the transport of monocarboxylates within enterocytes towards the blood circulation or an internal milieu.…”

Section: Coexpression or Differential Expression Of Mct1 And Slc5a8?supporting

confidence: 55%

Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8

Iwanaga

Takebe

Kato³

et al. 2006

Biomed. Res.

136

114

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Short-chain fatty acids (SCFA) are monocarboxylates produced by bacterial fermentation that play a crucial role in maintaining homeostasis in the large intestine. Two major transporters for SCFA, monocarboxylate transporter (MCT) and slc5a8 (or SMCT), exist in the digestive tract. The present histochemical study using in situ hybridization and immunohistochemistry revealed the distribution and subcellular localization of the MCT family in the digestive tract of mice, rats, and humans, comparing these with that of slc5a8. The expression of mucosal MCT1 in the mouse and rat was most intense in the cecum, followed by the colon, but low in the stomach and small intestine. Among other MCT subtypes, only MCT2 was detected in the parietal cell region of the gastric mucosa. Slc5a8 had predominant expression sites in the distal half of the large bowel and in the most terminal ileum. The mucosal MCT1 was localized in the basolateral membrane of enterocytes, while slc5a8 was restricted to the apical cell membrane, suggesting the involvement of slc5a8 in the uptake of luminal SCFA, and of MCT1 in the effl ux of SCFA and monocarboxylate metabolites towards blood circulation. The large intestine expressed both types of the transporter, but their distribution patterns differed along the longitudinal axis of the intestine and along the perpendicular axis of the mucosa.Plant-derived dietary fi ber and undigested carbohydrates are fermented by bacterial microfl ora in the large intestine and produce acetate, propionate, and butyrate, collectively called short-chain fatty acids (SCFA). These are monocarboxylates which contain less than fi ve carbon atoms: acetate has two carbons, propionate has three, and butyrate has four. The SCFA in the bowel lumen have some effects on the intestinal wall, including the stimulation of colonic blood fl ow and of fl uid and electrolyte uptake (30). Butyrate also functions as an energy source of epithelial cells in the large intestine and promotes differentiation of the cells (2, 21) while suppressing the proliferation of tumor cells by the induction of apoptosis (6). Thus, direct and indirect intraluminal supplementation of butyrate maintains and strengthens the epithelial integrity to suppress mucosal damage such as ulcerative colitis (15,16,19,27). At least 60% of the SCFA uptake in the large intestine occurs by simple diffusion of the unionized form across the cell membrane; the remainder occurs by the active cellular uptake of ionized SCFA involving co-transport of inorganic protons, such as Na + , K + , and H + (7). As a transporter of SCFA, monocarboxylate transporter (MCT)-1 was fi rst identifi ed and localized in intestinal epithelial cells as well as the heart, kidney, and epididymis (9). MCT1 can transport lactate, pyruvate, and SCFA in a H + -dependent manner. The

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Section: Coexpression or Differential Expression Of Mct1 And Slc5a8?supporting

confidence: 55%

Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8

Iwanaga

Takebe

Kato³

et al. 2006

Biomed. Res.

136

114

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“…We used lactic acid as an alternative carbon source to glucose because of its physiological relevance. Lactic acid is found in ingested foods, generated by lactic acid bacteria in the GI and urogenital tracts (29), and is essential for the proliferation of Candida glabrata in the intestinal tract (30). Lactic acid is also a component of isotonic solutions used in surgery or burn injury (e.g., lactated Ringer's solutions, Hartmann's solution), factors that increase the risk of systemic candidiasis (1).…”

mentioning

confidence: 99%

Growth of Candida albicans Cells on the Physiologically Relevant Carbon Source Lactate Affects Their Recognition and Phagocytosis by Immune Cells

et al. 2013

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bCandida albicans is a normal resident of the human gastrointestinal and urogenital tracts and also a prevalent fungal pathogen. During both commensalism and infection, it must match the immunological defenses of its host while adapting to environmental cues and the local nutrient status. C. albicans regularly colonizes glucose-poor niches, thereby depending upon alternative carbon sources for growth. However, most studies of host immune responses to C. albicans have been performed on fungal cells grown on glucose, and the extent to which alternative physiologically relevant carbon sources impact innate immune responses has not been studied. The fungal cell wall is decorated with multifarious pathogen-associated molecular patterns and is the main target for recognition by host innate immune cells. Cell wall architecture is both robust and dynamic, and it is dramatically influenced by growth conditions. We found that growth of C. albicans cells on lactate, a nonfermentative carbon source available in numerous anatomical niches, modulates their interactions with immune cells and the resultant cytokine profile. Notably, lactate-grown C. albicans stimulated interleukin-10 (IL-10) production while decreasing IL-17 levels, rendering these cells less visible to the immune system than were glucose-grown cells. This trend was observed in clinical C. albicans isolates from different host niches and from different epidemiological clades. In addition, lactate-grown C. albicans cells were taken up by macrophages less efficiently, but they were more efficient at killing and escaping these phagocytic cells. Our data indicate that carbon source has a major impact upon the C. albicans interaction with the innate immune system.

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“…1 The liver is the principal organ responsible for the removal of plasma lactates, accounting for 40% to 50% of whole-body lactate clearance under basal conditions. 4 In this case, excessive production of lactate in the circulation was presumably caused by blood transfusion and the visceral ischemia that occurs with portal vein clamping, as reported during orthotopic liver transplantation. 5 The excess lactate could not be metabolized by the liver during surgery because of the TVO.…”

Section: Discussionmentioning

confidence: 64%

Prolonged lactic acidosis after extended hepatectomy under in situ hypothermic perfusion

Davidson¹,

Rai²

1999

Liver Transpl

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A 46-year-old woman underwent right extended hepatectomy under total vascular occlusion with in situ hypothermic perfusion for colorectal metastasis. Immediately after surgery, she developed severe lactic acidosis, which required correction with sodium bicarbonate solution and ventilatory support for 36 hours. After 2 days, her lactate normalized, and the acidosis was corrected. She made an uneventful recovery. Persistent lactic acidosis after major hepatic resection under in situ hypothermic perfusion is a rare but reversible problem.Copyright 1999 by the American Association for the Study of Liver Diseases T otal vascular occlusion (TVO) with in situ hypothermic perfusion has been described for major hepatic resections for malignant primary and secondary liver tumors, as well as for benign liver disease. 1,2 Lactic acidosis occurs during vascular inflow occlusion and reverses with revascularization. 3 Persistent but reversible lactic acidosis after hepatectomy under TVO with in situ hypothermic perfusion has not been reported. Case ReportFour months after a low anterior resection for Dukes C stage carcinoma of the rectum, a 46-year-old woman was found to have a hepatic metastasis replacing segment 5 through 8 of the liver with a separate lesion in segment 4. The Tumor involved the right and middle hepatic veins and was adjacent to the left hepatic vein. There was no extrahepatic disease. Extended right hepatectomy with possible local resection of the left hepatic vein was planned under TVO. Venovenous bypass was used. The left liver was perfused with 3 L of University of Wisconsin solution at a temperature of 4°C. TVO continued for 75 minutes, during which an extended right hepatic resection was completed and the tumor was removed without resection of the left hepatic vein. There were no hypotensive episodes during the surgery, and circulating volume was maintained by using crystalloid and transfusing 7 U of blood. Body core temperature was 35.5°C immediately after surgery. Intraoperative and postoperative monitoring by pulse oximetry and arterial blood gas analysis showed that oxygen saturation was maintained within the normal range. After surgery, the patient was found to have metabolic acidosis, with a pH of 7.19, a base deficit of 13, and serum lactate level of 13.9 mmol/L. The acidosis was corrected with 50 mmol/L of sodium bicarbonate in a single dose intravenously, and artificial ventilation was maintained. Although the patient remained acidotic for 36 hours, with a lactate level of 11.7 to 14.8 mmol/L and a pH of 7.2 to 7.27, she did not require further sodium bicarbonate because her pH remained greater than 7.2. Liver function test results and lactate levels are listed in Table 1. DiscussionVascular isolation and hypothermic perfusion allows extensive hepatic resection to be performed with reduced blood loss and ischemic injury. 1 The liver is the principal organ responsible for the removal of plasma lactates, accounting for 40% to 50% of whole-body lactate clearance under basal conditions. 4 In this ...

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Regulation of lactate metabolism in vivo

Cited by 67 publications

References 76 publications

Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8

Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8

Growth of Candida albicans Cells on the Physiologically Relevant Carbon Source Lactate Affects Their Recognition and Phagocytosis by Immune Cells

Prolonged lactic acidosis after extended hepatectomy under in situ hypothermic perfusion

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