p1. Heat output by suspensions of isolated rat hepatocytes was determined by using a modified batch-type microcalorimeter. 2. The ratio of Osub2/sub uptake (determined polarographically) to heat output was used to assess the metabolic efficiency of isolated hepatocytes. 3. Cells from starved or fed rats incubated in either bicarbonate-buffered physiological saline containing gelatin, or bicarbonate-buffered physiological saline containing amino acids, serum albumin and glucose showed no significant difference with respect to the ratio of Osub2/sub uptake to heat output. 4. For liver cells from 24h-starved rats, the addition of 10mm-dihydroxyacetone and 2.5mm-fructose significantly decreased the ratio of Osub2/sub uptake to heat output from 1.94±0.05 in the controls to 1.52±0.04 and 1.54±0.01μmol/J respectively. 5. Glucagon (1μm), which slightly increased both Osub2/sub uptake and heat output, did not significantly alter the ratio. 6. The addition of extracellular 10mm-NHsub4/subCl and urease to provide an energetically wasteful cycle by ensuring hydrolysis of newly synthesized urea, lowered the ratio of Osub2/sub uptake to heat output from 1.81±0.08 to 1.47±0.06μmol/J, indicating a reduced metabolic efficiency. 7. Metabolic efficiency in rats of different dietary regimen, age and genetically based obesity was also assessed. No differences in the ratio of Osub2/sub uptake to heat output were found between liver cell suspensions prepared from rats maintained on colony diet and high-fat diet or sucrose-rich diet nor between animals ranging from 38 to 179 days of age. Comparison of the ratio of liver cell Osub2/sub uptake to heat output between homozygote Zucker ifa/fa/i obese rats and their lean littermates showed no significant difference. 8. It is concluded that the ratio of Osub2/sub uptake to heat output for isolated hepatocytes is relatively constant unless perturbed by conditions that markedly enhance substrate cycling./p
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