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Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats.

Bauerly K, Harris C, Chowanadisai W, Graham J, Havel PJ, Tchaparian E, Satre M, Karliner JS, Rucker RB - PLoS ONE (2011)

Bottom Line: Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ- vs.Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes.Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function.

View Article: PubMed Central - PubMed

Affiliation: Nutrition, University of California Davis, Davis, California, United States of America.

ABSTRACT
We have reported that pyrroloquinoline quinone (PQQ) improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ-) or 2 mg PQQ/Kg diet (PQQ+). Measurements included: 1) serum glucose and insulin, 2) total energy expenditure per metabolic body size (Wt(3/4)), 3) respiratory quotients (in the fed and fasted states), 4) changes in plasma lipids, 5) the relative mitochondrial amount in liver and heart, and 6) indices related to cardiac ischemia. For the latter, rats (PQQ- or PQQ+) were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ- vs. PQQ+ rats and energy expenditure (fed state) was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ- rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ- rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function.

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Relationship between relative mitochondrial amount (liver) and energy expenditure.In panel A the relationship between mitochondrial amount (mtDNA/nuclearDNA ratio) and energy expenditure in the light fed (squares) and dark fed (circles) for weanling rats fed PQQ- (open, n = 6) or PQQ+ (closed, n = 5) diets are shown; R∼0.6. Little or no relationship was observed when rats were fasted (⋄,PQQ-;⧫, PQQ+). In panel B, the average energy expenditure in both fed states minus the fasted state are compared. (Light and dark fed states) - (fasted state) are expressed relative to the mtDNA/nuclearDNA ratio. R was increased to ∼0.9. In panel C are data for the relative mitochondrial amount (mtDNA/nuclearDNA ratio). The average difference mitochondrial amount (∼10 %) was not significant for rats that were randomly selected out of a pool of 10 for each group (see Figure 6). In panel D are values for the fed and fasted states. The average decrease in total energy expenditure (PQQ- vs PQQ+) approached significance (p<0.1), when values for the fasted state (taken as a rough approximation of basal energy) were subtracted from the values for the two fed states (light and dark).
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pone-0021779-g008: Relationship between relative mitochondrial amount (liver) and energy expenditure.In panel A the relationship between mitochondrial amount (mtDNA/nuclearDNA ratio) and energy expenditure in the light fed (squares) and dark fed (circles) for weanling rats fed PQQ- (open, n = 6) or PQQ+ (closed, n = 5) diets are shown; R∼0.6. Little or no relationship was observed when rats were fasted (⋄,PQQ-;⧫, PQQ+). In panel B, the average energy expenditure in both fed states minus the fasted state are compared. (Light and dark fed states) - (fasted state) are expressed relative to the mtDNA/nuclearDNA ratio. R was increased to ∼0.9. In panel C are data for the relative mitochondrial amount (mtDNA/nuclearDNA ratio). The average difference mitochondrial amount (∼10 %) was not significant for rats that were randomly selected out of a pool of 10 for each group (see Figure 6). In panel D are values for the fed and fasted states. The average decrease in total energy expenditure (PQQ- vs PQQ+) approached significance (p<0.1), when values for the fasted state (taken as a rough approximation of basal energy) were subtracted from the values for the two fed states (light and dark).

Mentions: Data related to the effects of changing PQQ status on RQ, VO2, VCO2, and estimated energy expenditure are given in Figures 7 and 8. Although there was little change in RQ levels with respect to treatments, there was a significant difference in actual energy expenditure, which could be positively correlated with mitochondrial amount during periods when the rats were most active (see Discussion).


Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats.

Bauerly K, Harris C, Chowanadisai W, Graham J, Havel PJ, Tchaparian E, Satre M, Karliner JS, Rucker RB - PLoS ONE (2011)

Relationship between relative mitochondrial amount (liver) and energy expenditure.In panel A the relationship between mitochondrial amount (mtDNA/nuclearDNA ratio) and energy expenditure in the light fed (squares) and dark fed (circles) for weanling rats fed PQQ- (open, n = 6) or PQQ+ (closed, n = 5) diets are shown; R∼0.6. Little or no relationship was observed when rats were fasted (⋄,PQQ-;⧫, PQQ+). In panel B, the average energy expenditure in both fed states minus the fasted state are compared. (Light and dark fed states) - (fasted state) are expressed relative to the mtDNA/nuclearDNA ratio. R was increased to ∼0.9. In panel C are data for the relative mitochondrial amount (mtDNA/nuclearDNA ratio). The average difference mitochondrial amount (∼10 %) was not significant for rats that were randomly selected out of a pool of 10 for each group (see Figure 6). In panel D are values for the fed and fasted states. The average decrease in total energy expenditure (PQQ- vs PQQ+) approached significance (p<0.1), when values for the fasted state (taken as a rough approximation of basal energy) were subtracted from the values for the two fed states (light and dark).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3140972&req=5

pone-0021779-g008: Relationship between relative mitochondrial amount (liver) and energy expenditure.In panel A the relationship between mitochondrial amount (mtDNA/nuclearDNA ratio) and energy expenditure in the light fed (squares) and dark fed (circles) for weanling rats fed PQQ- (open, n = 6) or PQQ+ (closed, n = 5) diets are shown; R∼0.6. Little or no relationship was observed when rats were fasted (⋄,PQQ-;⧫, PQQ+). In panel B, the average energy expenditure in both fed states minus the fasted state are compared. (Light and dark fed states) - (fasted state) are expressed relative to the mtDNA/nuclearDNA ratio. R was increased to ∼0.9. In panel C are data for the relative mitochondrial amount (mtDNA/nuclearDNA ratio). The average difference mitochondrial amount (∼10 %) was not significant for rats that were randomly selected out of a pool of 10 for each group (see Figure 6). In panel D are values for the fed and fasted states. The average decrease in total energy expenditure (PQQ- vs PQQ+) approached significance (p<0.1), when values for the fasted state (taken as a rough approximation of basal energy) were subtracted from the values for the two fed states (light and dark).
Mentions: Data related to the effects of changing PQQ status on RQ, VO2, VCO2, and estimated energy expenditure are given in Figures 7 and 8. Although there was little change in RQ levels with respect to treatments, there was a significant difference in actual energy expenditure, which could be positively correlated with mitochondrial amount during periods when the rats were most active (see Discussion).

Bottom Line: Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ- vs.Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes.Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function.

View Article: PubMed Central - PubMed

Affiliation: Nutrition, University of California Davis, Davis, California, United States of America.

ABSTRACT
We have reported that pyrroloquinoline quinone (PQQ) improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ-) or 2 mg PQQ/Kg diet (PQQ+). Measurements included: 1) serum glucose and insulin, 2) total energy expenditure per metabolic body size (Wt(3/4)), 3) respiratory quotients (in the fed and fasted states), 4) changes in plasma lipids, 5) the relative mitochondrial amount in liver and heart, and 6) indices related to cardiac ischemia. For the latter, rats (PQQ- or PQQ+) were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ- vs. PQQ+ rats and energy expenditure (fed state) was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ- rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ- rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function.

Show MeSH
Related in: MedlinePlus