Comparative Effects of Pyrroloquinoline Quinone (PQQ) and Resveratrol (RSV) on Mitochondriogenesis in Mice

Abstract

Objectives and Hypothesis Many phytochemicals and biofactors influence mitochondrial function, lipid deposition, and oxidative metabolism. Examples include phytoalexins, flavonoids, and quinones, such as PQQ. Herein, PQQ is compared to RSV (a phytoalexin). Animal tissues retain nM concentrations of PQQ, which promote NAD+ production and sirtuin-related mitochondriogenesis. For example, PQQ promotes mitochondriogenesis in animal models when fed at 0.5 mg PQQ or more/Kg of diet. Such effects elicited by RSV often require 100X or more those amounts. Accordingly, we hypothesize that many of the responses ascribed to RSV may be due to compounds like PQQ or PQQ-derivatives. (cf. Chowanadisai et al., J of Biol Chem 285, 2010:142-52). Methods Two experiments were performed. (Exp. 1) Swiss-derived CD-1 mice express excessive weight gain and fat deposition when exposed to high-fat diets. A goal was to determine if PQQ can attenuate such increases in weight or fat deposition. The mice were maintained in keeping with the FASEB Principles for the Use of Animals in Research and Education. Groups of mice were fed either a low-fat (LFD, 5%) or high-fat (HFD, 20%) casein-based diet with or without PQQ addition at 10 mg/Kg diet for 4 weeks. (Exp.2) Adult C-57BL mice (4-6 months old) were used with or without PQQ addition at 10 mg/Kg diet or RSV at 400 mg/Kg diet. Liver, brown fat, and muscle were examined. The relative numbers of mitochondria were estimated using real-time PCR methods to assess mtDNA/nuclearDNA expression to compare PQQ vs. RSV responses. PQQ in plasma was measured using chemical and mass spectrometric methods. Results (Exp 1) PQQ attenuated the increase in body weight and fat in mice fed the high-fat diet (p<0.05). Mice fed the high-fat diet (-PQQ) weighed 40+/-3 g. Those receiving the high-fat diet (+PQQ) or those containing 5% fat weighed 27 to 32 g. PQQ exposure reduced body fat by 50 % or more**. The relative mtDNA/DNA concentrations in skeletal muscle for CD-1 mice were: 10.8 ± 3.3 (HFD-PQQ) vs. 15.1±1.2 (HFD+PQQ)*, and 18.5 ± 3.0 (LFD-PQQ) vs. 20. 8 ± 3.9 (LFD+PQQ). (Exp.2) PQQ at 1/40th the dietary dose as RSV promoted mtDNA stimulation in liver, brown fat, and skeletal muscle. As a percentage of control values, the mtDNA/DNA ratios, although variable, were increased by 113% and 111% following RSV and PQQ exposures, respectively. For brown fat, the values were 115% and 129% for RSV (NS) and PQQ**, respectively. For skeletal muscle, the values were 104% and 113% for RSV (NS) and PQQ**, respectively. The addition of PQQ to diets markedly enhanced plasma PQQ levels (3±2 pmol PQQ/mL, control; 17±4 pmol PQQ/mL, PQQ suppl.). Of interest, exposure to RSV also increased plasma PQQ (6.5±2 pmol PQQ/mL). [NS=not significant, *=p<0.05, **=0.01] Conclusions and Comments PQQ promotes mitochondriogenesis at lower dietary intakes compared to RSV. For the current observations, 10 mg of PQQ/Kg of diet promoted mtDNA changes equivalent to doses of 400 mg of RSV/ Kg of diet. The data also indicate that PQQ at low levels of exposure normalizes body weight and fat in suspectable mice exposed to a high-fat diet.