Increased lipogenesis in isolated hepatocytes from cold-acclimated ducklings.

Thermogenic endurance and development of metabolic cold adaptation in birds may critically depend on their ability to synthesize and use fatty acids (FA) as fuel substrates. Hepatic lipogenesis and the capacity to oxidize FA in thermogenic tissues were measured in cold-acclimated (CA) ducklings (Cairina moschata) showing original mechanisms of metabolic cold adaptation in the absence of brown adipose tissue, the specialized thermogenic tissue of rodents. The rate of FA synthesis from [U-(14)C]glucose and from [1-(14)C]acetate, measured in incubated hepatocytes isolated from 5-wk-old thermoneutral (TN; 25 degrees C) or CA (4 degrees C) fed ducklings, was higher than in other species. Hepatic de novo lipogenesis was further increased by cold acclimation with both glucose (+194%) and acetate (+111%) as precursor. Insulin slightly increased (+11-14%) hepatic lipogenesis from both precursors in CA ducklings, whereas glucagon was clearly inhibitory (-29 to -51%). Enhanced de novo lipogenesis was associated with higher (+171%) hepatocyte activity of glucose oxidation and larger capacity (+50 to +100%) of key lipogenic enzymes. The potential for FA oxidation was higher in liver (+61%) and skeletal muscle (+29 to +81%) homogenates from CA than from TN ducklings, suggesting that the higher hepatic lipogenesis may fuel oxidation in thermogenic tissues. Present data underline the high capacity to synthesize lipids from glucose in species like muscovy ducks susceptible to hepatic steatosis. Lipogenic capacity can be further increased in the cold and may represent an important step in the metabolic adaptation to cold of growing ducklings.

Effect of cold-acclimation on oxygen uptake and glucose production of perfused duckling liver.

The control of hepatic metabolism by substrates and hormones was assessed in perfused liver from young Muscovy ducklings. Studies were performed in fed or 24-h fasted 5-week-old thermoneutral (25 degrees C; TN) or cold-acclimated ducklings (4 degrees C; CA) and results were compared with those obtained in rats. Basal oxygen uptake of perfused liver (LVO2) was higher after cold acclimation both in fed (+65%) and 24-h fasted (+29%) ducklings and in 24-h fasted rats (+34%). Lactate (2 mM), the main gluconeogenic substrate in birds, similarly increased LVO2 in both TN and CA ducklings and the effect was larger after fasting. Both glucagon and norepinephrine dose-dependently increased LVO2 in ducklings and rats, but cold acclimation did not improve liver response and liver sensitivity to norepinephrine in ducklings was even reduced in CA animals. Liver contribution to glucagon-induced thermogenesis in vivo was estimated to be 22% in TN and 12% in CA ducklings. Glucagon stimulated gluconeogenesis from lactate in duckling liver and the stimulation was 2.2-fold higher in CA than in TN fasted birds. These results indicate a stimulated hepatic oxidative metabolism in CA ducklings but hepatic glucagon-induced thermogenesis (as measured by LVO2) was not improved. A role of the liver is suggested in duckling metabolic acclimation to cold through an enhanced hepatic gluconeogenesis under glucagon control.

Comparison of glycogen store in two strains of rat and guinea-pig under fed and fasted conditions.

Glycogen content in the liver, skeletal muscle and heart has been determined in Sprague-Dawley (SD) and Wistar (W) rats and in tricoloured (T) and albino Dunkin Hartley (DH) guinea-pigs. The 12-week-old animals were studied under non-fasted or control conditions (N) and after 48 hr of fast (F48). Hepatic glycogen was higher in DH guinea-pigs (95.6 +/- 3.8 mg g-1) than in W (77.2 +/- 5.3 mg g-1) and SD (80.2 +/- 2.3 mg g-1) rats under N conditions. Mean values for the two strains were slightly higher in guinea-pigs than in rats. After fasting, hepatic glycogen was almost exhausted in the two species but was higher in W (1.5 +/- 0.08 mg g-1) and T (1.5 +/- 0.2 mg g-1) than in SD and DH (0.6 +/- 0.1 mg g-1). The content of glycogen in the anterior muscles of the thigh was comparable in the two strains of rat and guinea-pig, but was twice as high in the guinea-pigs (DH:15.1 +/- 0.6; T: 16.4 +/- 0.7 mg g-1) as in the rats (SD: 8.1 +/- 0.2; W: 7.1 +/- 0.5 mg g-1) under N conditions. In F48 animals, muscular glycogen decreased by 41-46% (rats) and 38-39% (guinea-pigs). Hepatic and extra-liver glycogen stores were calculated and found higher in the guinea-pigs than in the rats. The total utilization during fasting was larger in the guinea-pigs (6140 mg/kg body wt) than in the rats (4500 mg/kg body wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Substrates for cold thermogenesis in thyrotoxic dogs.

The influence of thyrotoxicosis on energy supply during cold exposure was studied in normal and chronically thyroxine (T4)-treated normothermic dogs exposed to neutral (Ta,N = +25 degrees C) or cold (Ta,C = -21 degrees C) ambient temperatures. At Ta,N, T4 treatment significantly increased VO2, glucose turnover, and plasma 3-hydroxybutyrate concentration. The percentage of glucose turnover derived from alanine also increased in spite of lower alanine release. In cold, T4 treatment did not significantly modify O2 consumption, glucose turnover, or plasma alanine concentration, but plasma hydroxybutyrate, alanine clearance, and alanine conversion into glucose were significantly increased compared with control. It is suggested that in cold the main effect of thyrotoxicosis on energy supply, in addition to a trend toward lipid mobilization, is an increase in hepatic alanine extraction and conversion into glucose in the presence of lower muscular alanine delivery.

Effect of cold ambient temperature on glucose and alanine turnover in dogs.

The metabolic effects of acute cold exposure were examined in dogs exposed to either +25 degrees C (TaN) or -21 degrees C (TaC). Simultaneous infusion of D-3-3H glucose and U-14C alanine was used to measure glucose (R Glu) and alanine carbon (R Ala) turnover rates. At the two ambient temperatures the animals remained normothermic and normoglycemic throughout the experiments. Cold exposure provoked a significant increase in VO2 (X 4.5), plasma 3-hydroxybutyrate concentration (X 1.8), R Glu (X 2.3) and alanine metabolic clearance (X 1.7), while plasma alanine concentration (X 0.4) and R Ala (X 0.6) were significantly decreased. At TaN and TaC, significant direct relationships were found between R (Ala) and plasma alanine concentration, the alanine fractional turnover rate being higher at TaC than at TaN. At the two ambient temperatures, inverse relationship was found between R (Ala) and plasma 3-hydroxybutyrate concentration. These experiments indicate that in spite of increased glucose needs, acute cold exposure is accompanied by reduced alanine release. They suggest that alanine plays only a minor role in cold-stimulated gluconeogenesis in dogs.

Independence of circulating insulin levels of the increased glucose turnover in shivering dogs.

In dogs, selective insulin deficiency induced by simultaneous somatostatin and glucagon infusion does not alter the high rate of glucose utilization provoked by acute cold exposure. However, both in resting and in shivering dogs, lowering of plasma insulin decreases plasma glucose metabolic clearance significantly.

Combined effects of cold and somatostatin on glucose kinetics in dogs.

The role of the endocrine pancreas in glucose production (Ra), utilization (Rd), and metabolic clearance (R'd) was investigated during acute exposure to cold in normal normothermic dogs. Two ambient temperatures (TaN = +25 degrees C and TaC = -21 degrees C) were selected. At TaC, metabolic rate and glucose turnover of the shivering dogs were 4.3 and 2.4 times, respectively, higher than in dogs resting at TaN. As compared with the pre-experimental period, somatostatin infusion at TaN induced a 25% (arterial) and 34% (portal) glucagon deficiency, while insulin concentration dropped by 59% (arterial) and 74% (portal). Similar values were obtained at TaC for glucagon (39% arterial and 47% portal) and for insulin (52% arterial and 56% portal). At TaN, these simultaneous hormonal alterations provoked a slight reduction in plasma glucose concentration which levelled down to 4.4 mM. This reduction was due to a decrease in Ra, followed by a parallel decrease in Rd whereas R'd remained unchanged. At TaC, plasma glucose concentration dropped to the same level but quickly rose again during somatostatin infusion. This rise was due to a larger reduction in Rd than in Ra, accompanied by an abrupt fall in R'd. This reduction in R'd appears to be an important mechanism able to restore euglycemia during global pancreatic hormone deficiency in cold exposed dogs.

Reversible and irreversible glucose disposal in dogs: influence of fasting and cold exposure.

Rates of total glucose entry rate, irreversible loss, and recycling were measured in unanesthetized dogs with indwelling arterial and venous catheters. Four experimental conditions were selected: 16 or 26 hr of fasting and neutral (+25 degrees C) or cold (-21 degrees C) ambient temperatures. A mixture of U 14C-glucose and 2-3H-glucose was used as a tracer, according to the primed infusion technique. No matter what the ambient temperature was, increase of fasting time from 16 to 26 hr induced a slight, but nonsignificant, decrease in both the total glucose entry rate and the irreversible loss. At neutral ambient temperature, the amount of glucose promptly recycled was less after 16 hr than after 26 hr of fasting, while an opposite pattern was observed during cold exposure. Thus, that part of hepatic glucose entry promptly recycled was significantly increased from 22% (16 hr of fasting) to 31% (26 hr of fasting) at neutral ambient temperature. It remained almost unchanged (20% and 18%) in cold. It was, therefore, suggested that this increase might be considered as an compensatory mechanism, exerting a sparing effect on glucose utilization. This mechanism does not occur in cold ambient temperature, thus, worsening a possible shortage in glucose supply.