measuring-liver-mitochondrial-oxygen-consumption-proton-leak-kinetics

Measuring Liver Mitochondrial Oxygen Consumption and Proton Leak Kinetics to Estimate Mitochondrial Respiration in Holstein Dairy Cattle

Oxygen consumption, proton motive force (PMF) and proton leak are measurements of mitochondrial respiration, or how well mitochondria are able to convert ...

University of California Davis

Teaching comparative metabolism using a graphic computer model, Virtual Tissue.

Computer models used in ration formulation assume that nutrients supplied by a ration formulation are the same as the nutrients presented in front of the cow in the final ration. Deviations in nutrients due to feed management effects such as dry matter changes (i.e., rain), loading, mixing, and delivery errors are assumed to not affect delivery of nutrients to the cow and her resulting milk production. To estimate how feed management affects nutrients supplied to the cow and milk production, and determine if nutrients can serve as indexes of feed management practices, weekly total mixed ration samples were collected and analyzed for 4 pens (close-up cows, fresh cows, high-milk-producing, and low-milk-producing cows, if available) for 7 to 12 wk on 5 commercial California dairies. Differences among nutrient analyses from these samples and nutrients from the formulated rations were analyzed by PROC MIXED of SAS (SAS Institute Inc., Cary, NC). Milk fat and milk protein percentages did not vary as much [coefficient of variation (CV) = 18 to 33%] as milk yield (kg; CV = 16 to 47 %) across all dairies and pens. Variability in nutrients delivered were highest for macronutrient fat (CV = 22%), lignin (CV = 15%), and ash (CV = 11%) percentages and micronutrients Fe (mg/kg; CV = 48%), Na (%; CV = 42%), and Zn (mg/kg; CV = 38%) for the milking pens across all dairies. Partitioning of the variability in random effects of nutrients delivered and intraclass correlation coefficients showed that variability in lignin percentage of TMR had the highest correlation with variability in milk yield and milk fat percentage, followed by fat and crude protein percentages. But, variability in ash, fat, and lignin percentages of total mixed ration had the highest correlation with variability in milk protein percentage. Therefore, lignin, fat, and ash may be the best indices of feed management to include effects of variability in nutrients on variability in milk yield, milk fat, and milk protein percentages in ration formulation models.

Variation in nutrients formulated and nutrients supplied on 5 California dairies.

The goal of this research was to use a computational model of human metabolism to predict energy metabolism for lean and obese men. The model is composed of 6 state variables representing amino acids, muscle protein, visceral protein, glucose, triglycerides, and fatty acids (FAs). Differential equations represent carbohydrate, amino acid, and FA uptake and output by tissues based on ATP creation and use for both lean and obese men. Model parameterization is based on data from previous studies. Results from sensitivity analyses indicate that model predictions of resting energy expenditure (REE) and respiratory quotient (RQ) are dependent on FA and glucose oxidation rates with the highest sensitivity coefficients (0.6, 0.8 and 0.43, 0.15, respectively, for lean and obese models). Metabolizable energy (ME) is influenced by ingested energy intake with a sensitivity coefficient of 0.98, and a phosphate-to-oxygen ratio by FA oxidation rate and amino acid oxidation rate (0.32, 0.24 and 0.55, 0.65 for lean and obese models, respectively). Simulations of previously published studies showed that the model is able to predict ME ranging from 6.6 to 9.3 with 0% differences between published and model values, and RQ ranging from 0.79 to 0.86 with 1% differences between published and model values. REEs >7 MJ/d are predicted with 6% differences between published and model values. Glucose oxidation increases by ∼0.59 mol/d, RQ increases by 0.03, REE increases by 2 MJ/d, and heat production increases by 1.8 MJ/d in the obese model compared with lean model simulations. Increased FA oxidation results in higher changes in RQ and lower relative changes in REE. These results suggest that because fat mass is directly related to REE and rate of FA oxidation, body fat content could be used as a predictor of RQ. 

Computer modeling of obesity links theoretical energetic measures with experimental measures of fuel use for lean and obese men.

Mitochondria are central to metabolism, nutrition, and health, but many factors can influence their efficiency. The objectives of this study were to determine if the mitochondrial enzyme activities of citrate synthase, complex I, complex IV, and complex V from peripheral blood mononuclear cells in Holstein and Jersey dairy calves were affected by age or relative gain as a percent of initial weight. Twenty-three Holstein and 23 Jersey heifer calves were enrolled between 3 and 6 d of age and whole blood samples were collected via jugular venipuncture at 1, 2, and 8 wk of age. Crude mitochondrial extracts were obtained from the peripheral blood mononuclear cell fraction at each time point and subsequently assayed for enzymatic activity. Age-dependent changes in activity were observed in complex V for both breeds. In Jersey calves complex IV and citrate synthase activity differed with age. Complex I activity was greater for high relative gain Jerseys and tended to be greater for high relative gain Holstein calves. Holstein calves had greater incidence of scours compared with Jersey calves, and in both breeds scouring calves exhibited greater complex V activity compared with those without scours. These data suggest that age and immune challenge in the form of scours affect mitochondrial complex V activity. Additionally, complex I activity may serve as a marker for calf growth potential because it was influenced by relative gain and not age.

Heidi A. Rossow

Veterinary Medicine Teaching and Research Center

University of California Davis

Measuring Liver Mitochondrial Oxygen Consumption and Proton Leak Kinetics to Estimate Mitochondrial Respiration in Holstein Dairy Cattle

Heidi A. Rossow

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University of California Davis

Measuring Liver Mitochondrial Oxygen Consumption and Proton Leak Kinetics to Estimate Mitochondrial Respiration in Holstein Dairy Cattle

Veterinary Medicine Teaching and Research Center