Low-carbohydrate, high-protein diets favorably affect body mass and composition independent of energy intake, which in part supports the proposed metabolic advantage of these diets.

BACKGROUND & AIMS Zinc homeostasis in cells is maintained through tight regulation of zinc influx, efflux, and distribution to intracellular organelles by zinc transporters. The Zrt-Irt-like protein (ZIP) transporters facilitate zinc influx to the cytosol. Expression of the ZIP family member Zip14 can be induced by inflammatory cytokines, which also initiate liver regeneration. Hepatocyte proliferation is required for liver regeneration. Zinc regulates cell proliferation, tissue growth, and many mitogenic signaling pathways; we investigated its role in hepatocytes. METHODS Wild-type and Zip14−/− mice that underwent partial hepatectomy (70% of liver removed) were used as models of liver regeneration. We also analyzed AML12 hepatocytes that overexpressed Zip14. Proliferation was assessed with proliferating cell nuclear antigen, CD1, and Ki67 markers and along with assays of zinc content was related to protein tyrosine phosphatase 1B (PTP1B) and extracellular signal–regulated kinase 1/2 signaling. RESULTS Zip14 was up-regulated and hepatic zinc content increased during liver regeneration. Increased hepatic zinc inhibited activity of the phosphatase PTP1B and increased phosphorylation of c-Met, which promoted hepatocyte proliferation. AML12 cells that overexpressed Zip14 increased in zinc content and proliferation; PTP1B was inhibited and phosphorylation of c-Met increased. The increases in hepatic levels of zinc and hepatocyte proliferation that occurred following partial hepatectomy were not observed in Zip14−/− mice. CONCLUSIONS The transporter Zip14 mediates hepatic uptake of zinc during liver regeneration and for hepatocyte proliferation. These findings indicate that zinc transporter activity regulates liver tissue growth by sequestering zinc. Reagents that regulate ZIP14 activity might be developed as therapeutics to promote liver regeneration in patients with chronic liver disease.

Vitamin B-6 deficiency is associated with impaired tryptophan metabolism because of the coenzyme role of pyridoxal 5'-phosphate (PLP) for kynureninase and kynurenine aminotransferase. To investigate the underlying mechanism, we developed a mathematical model of tryptophan metabolism via the kynurenine pathway. The model includes mammalian data on enzyme kinetics and tryptophan transport from the intestinal lumen to liver, muscle, and brain. Regulatory mechanisms and inhibition of relevant enzymes were included. We simulated the effects of graded reduction in cellular PLP concentration, tryptophan loads and induction of tryptophan 2,3-dioxygenase (TDO) on metabolite profiles and urinary excretion. The model predictions matched experimental data and provided clarification of the response of metabolites in various extents of vitamin B-6 deficiency. We found that moderate deficiency yielded increased 3-hydroxykynurenine and a decrease in kynurenic acid and anthranilic acid. More severe deficiency also yielded an increase in kynurenine and xanthurenic acid and more pronounced effects on the other metabolites. Tryptophan load simulations with and without vitamin B-6 deficiency showed altered metabolite concentrations consistent with published data. Induction of TDO caused an increase in all metabolites, and TDO induction together with a simulated vitamin B-6 deficiency, as has been reported in oral contraceptive users, yielded increases in kynurenine, 3-hydroxykynurenine, and xanthurenic acid and decreases in kynurenic acid and anthranilic acid. These results show that the model successfully simulated tryptophan metabolism via the kynurenine pathway and can be used to complement experimental investigations.

A method for total parenteral nutrition in the mouse was developed using commercially available supplies and equipment. The mouse's inferior vena cava was catheterized and the catheter was exteriorized from the tail. Mice (average body weight 22.5 g) were not tethered but instead were partially restrained by immobilizing the tail to protect the infusion tubing. A solution was formulated to contain 40% dextrose and 4.3% amino acids plus vitamins, electrolytes, and trace elements. It was administered via pump in graded fashion for the first 3 days to allow the mice to adapt, and then at a rate of 8 ml/day thereafter. This volume provided approximately 12 kcal and 54 mg nitrogen per day and was calculated to meet the needs of the mouse fed per os according to guidelines of the National Research Council. During the adaptation period mice lost weight but they were in positive N balance thereafter. At the end of 12 days body weight was not different than at the start, indicating the adequacy of nutrient input. Further, there were no differences in nitrogen balance or body weight in total parenteral nutrition fed mice in comparison with tail-restrained mice given the same solution per os. All mice appeared to tolerate the partial restraint without incidence and showed no untoward side effects. The rationale and validity of this technique is discussed in detail.

The purpose of this study was to evaluate the early-phase muscular performance adaptations to 5 weeks of traditional (TRAD) and eccentric-enhanced (ECC+) progressive resistance training and to compare the acute postexercise total testosterone (TT), bioavailable testosterone (BT), growth hormone (GH), and lactate responses in TRAD- and ECC+-trained individuals. Twenty-two previously untrained men (22.1 +/- 0.8 years) completed 1 familiarization and 2 baseline bouts, 15 exercise bouts (i.e., 3 times per week for 5 weeks), and 2 postintervention testing bouts. Anthropometric and 1 repetition maximum (1RM) measurements (i.e., bench press and squat) were assessed during both baseline and postintervention testing. Following baseline testing, participants were randomized into TRAD (4 sets of 6 repetitions at 52.5% 1RM) or ECC+ (3 sets of 6 repetitions at 40% 1RM concentric and 100% 1RM eccentric) groups and completed the 5-week progressive resistance training protocols. During the final exercise bout, blood samples acquired at rest and following exercise were assessed for serum TT, BT, GH, and blood lactate. Both groups experienced similar increases in bench press (approximately 10%) and squat (approximately 22%) strength during the exercise intervention. At the conclusion of training, postexercise TT and BT concentrations increased (approximately 13% and 21%, respectively, p < 0.05) and GH concentrations increased (approximately 750-1200%, p < 0.05) acutely following exercise in both protocols. Postexercise lactate accumulation was similar between the TRAD (5.4 +/- 0.4) and ECC+ (5.6 +/- 0.4) groups; however, the ECC+ group's lactate concentrations were significantly lower than those of the TRAD group 30 to 60 minutes into recovery. In conclusion, TRAD training and ECC+ training appear to result in similar muscular strength adaptations and neuroendocrine responses, while postexercise lactate clearance is enhanced following ECC+ training.