Increased contribution of brown adipose tissue to nonshivering thermogenesis in the Djungarian hamster during cold-adaptation

Summary The effect of cold-adaptation was investigated on the brown adipose tissue of Djungarian hamsters. Animals maintained at 23°C and 16 hours light per day (controls) were exposed to 5°C. The wet weight of the total brown fat is reduced by some 40% within 4 days of coldexposure, as a result of extensive triacylglycerol depletion of the tissue with no reduction in DNA; the tissue mass remains constant unde persistent cold influence. The total amount of tissue mitochondria is doubled by 24 h and increases by a factor of 3 under persistent cold-stimulus, the specific respiratory capacity of the organelles remaining unchanged. The amount of 32 kDa regulatory protein per mg mitochondrial protein quantified from high-affinity GDP-binding, is increased by a factor of 2.7 after 21 days of cold-adaptation; a 9-fold increment is found of the total mitochondrial GDB-binding capacity.Comparison of nonshivering thermogenesis and the maximal thermogenic capacity of brown fat, estimated from the maximal respiration of the isolated mitochondria and the total amount of mitochondria in the tissue, suggests that brown fat may contribute about 20% to the whole-body nonshivering thermogenesis in warm-adapted controls and 45% in cold-adapted hamsters. The estimated increase in thermogenic capacity of the tissue in response to 21 days of cold-adaptation corresponds to the increase in nonshivering thermogenesis, suggesting a central thermoregulatory role of brown fat during cold-adaptation.Abbreviation FCCP carbonylcyanide-p-trifluoromethoxyphenylhydrazone     

Organ blood flow and brown adipose tissue oxygen consumption during noradrenaline-induced nonshivering thermogenesis in the Djungarian hamster

During NA-induced NST blood flow through BAT increased from 0.18 ml min-1 to 3.21 ml min-1 in 23 degrees C acclimated (equals thermoneutrality) and from 0.61 ml min-1 to 9.67 ml min-1 in outdoors (-2 to 12 degrees C Ta) acclimated Djungarian hamsters. In 23 degrees C acclimated hamsters this increase was accomplished by a diversion of blood flow from visceral organs without a change in cardiac output (19.7 versus 20.5 ml min-1 before and after NA). In outdoors acclimated hamsters we also observed a redistribution of blood flow from the viscera to BAT. In addition, cardiac output increased from 24.3 to 38.8 ml min-1. Metabolic rate of BAT in situ was determined from organ blood flow and the (A-V)O2 of blood across the interscapular BAT. BAT of outdoor acclimated hamsters showed a significantly higher metabolism in comparison to 23 degrees C acclimated hamsters (81.1 versus 30.4 mlO2h-1). Furthermore, this calculation revealed that 28% (23 degrees C acclimated hamsters) and 61% (outdoors acclimated hamsters) of total NST were located in BAT of Phodopus sungorus.     

Seasonal adaptation of brown adipose tissue in the Djungarian hamster

Summary The composition and oxidative capacity of brown adipose tissue (BAT) were investigated in Djungarian hamsters kept under natural photoperiod, either indoors at neutralT _a (23°C) or under outdoor conditions. BAT comprises up to 5% of the body weight in summer/indoor hamster, with lipid representing 86% of the total tissue mass. Tissue mass and thermogenic capacity are inversely related during seasonal adaptation: 30% decrease of total DNA, accompanied by extensive lipid depletion, reduces the amount of BAT by almost 60% during acclimatization from summer/indoor to winter/outdoor conditions. Mitochondrial protein in BAT is increased by a factor of 2.6 concomitantly, and by a factor of 4 when related to body weight (body weight reduction 36%).Cytochrome oxidase activity in different brown fat deposits varies by up to 150% in summer/indoor hamsters; depending on the fat pad, the enzyme activity is increased 200%–700% during adaptation to winter/outdoor conditions.Natural photoperiod is decisive in determining the seasonal adaptation of DNA content in BAT and of body weight. Short photoperiod alone may lead to depletion of lipid content of BAT and thus decrease the tissue mass practically to the lowest seasonal level, even though both parameters may be also influenced byT _a. One third of the maximum adaptive increase of tissue mitochondria may be attributed to seasonal changes in photoperiod and up to two thirds toT _a. Photoperiod establishes a fixed fundament of slow-reacting functional adaptation of BAT, whereas the effect of decreasedT _a depends on the rate and duration of cold influence.Abbreviations BAT brown adipose tissue - NST nonshivering thermogenesis - T _a ambient temperature     

Absence of UCP3 in brown adipose tissue does not impair nonshivering thermogenesis

We report on a novel Djungarian hamster mutant lineage that exhibits a loss of uncoupling protein (UCP) 3 mRNA and protein in brown adipose tissue (BAT), whereas UCP3 expression in skeletal muscle is only mildly diminished. In response to 2 d of cold exposure, UCP3 mRNA was 4.5-fold elevated in BAT of wild-type hamsters but remained undetectable in mutant hamsters. Notably, in BAT of warm- and cold-exposed mutant hamsters, UCP1 and UCP2 mRNA levels were increased. The tissue specificity of UCP3 deficiency suggests that the underlying unknown mutation impairs a factor controlling UCP3 gene expression selectively in brown adipocytes. In wild-type but not mutant primary brown adipocytes, UCP3 gene expression was stimulated by treatment with peroxisome proliferator activated receptor (PPAR) ligands. This implies that the underlying mutation causing UCP3 deficiency is expressed within brown adipocytes and disrupts PPAR-dependent transactivation of the UCP3 gene. On the functional level, we found no direct phenotypic consequences of altered UCP expression in BAT. The absence of UCP3 in BAT of cold-acclimated mutant hamsters affected neither maximal nonshivering thermogenesis elicited by noradrenaline nor the uncoupled respiration of isolated mitochondria in the presence of oligomycin and in response to palmitate.     

Apparent dissociation between sympathetic activity and brown adipose tissue thermogenesis during pregnancy and lactation in golden hamsters

Sympathetic activity has been assessed by measurements of noradrenaline turnover in brown adipose tissue and in the heart of golden hamsters during pregnancy and lactation. Noradrenaline turnover was not significantly altered in either tissue in pregnant or lactating hamsters, despite the atrophy of brown adipose tissue that occurs during reproduction. This suggests that sympathetic activity and brown adipose tissue thermogenesis are dissociated during pregnancy and lactation in golden hamsters. The results also indicate that the large increase in food intake lactation does not lead to a diet-induced stimulation of the sympathetic nervous system.     

Seasonal acclimation of bank voles and wood mice: nonshivering thermogenesis and thermogenic properties of brown adipose tissue mitochondria

Summary Seasonal acclimation of nonshivering thermogenesis and brown adipose tissue was studied in wild bank voles (Clethrionomys glareolus), yellow necked field mice and wood mice (Apodemus flavicollis, A. sylvaticus). Both, voles and mice increased their capacity for nonshivering thermogenesis during winter. Thermogenic properties of brown fat (cytochrome c oxidase activity, mitochondrial protein content, GDP-binding of brown fat mitochondria) showed similar changes during seasonal acclimation;Clethrionomys andApodemus spp. both showed lowest thermogenic properties in the summer during August, a rapid increase during fall, and highest levels of thermogenic activity in the winter months. With regard to changes in body weight and brown fat mass these species show different strategies for seasonal acclimation. InClethrionomys a reduction of body mass in the winter was found, both in the wild population as well as in individual animals housed in the laboratory.A. flavicollis showed a reduction of body weight during fall, whereasA. sylvaticus maintained a constant body mass throughout the year. Brown fat mass and cellularity increased in theApodemus spp. during winter, in parallel with the thermogenic properties of brown fat, whereas inClethrionomys brown fat mass and cellularity remained seasonally constant. These species live in the same habitat and were trapped in the same area. It is concluded that seasonal improvements of in vivo and in vitro thermogenesis are very similar in these species, although the physiological basis for this improvement is different inClethrionomys andApodemus.Abbreviations BAT brown adipose tissue - BMR basal metabolic rate (resting metabolic rate at thermoneutrality) - BW body weight - COX cytochrome c oxidase - GDP guanosine diphosphate - MP mitochondrial protein - NA noradrenaline - NST nonshivering thermogenesis - NSTcap NST capacity (NST maximum minus BMR) - T _a ambient temperature     

PITPNC1 promotes the thermogenesis of brown adipose tissue under acute cold exposure

Brown adipose tissue(BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein,cytoplasmic 1(PITPNC1) is identified as a lipid transporter that reciprocally transfers phospholipids between intracellular membrane structures. However, the physiological significance of PITPNC1 and its regulatory mechanism remain unclear. Here,we demonstrate that PITPNC1 is a key player in thermogenesis of BAT. While Pitpnc1^-/-mice do not differ with wildtype m...     

Impaired febrile response with age: role of thermogenesis in brown adipose tissue.

We demonstrated previously that in Escherichia coli-infected rats, the heat necessary for the febrile response is a result of thermogenesis in brown adipose tissue (BAT). To investigate whether senescent rats have an impaired febrile response to infection and whether such an impairment is a result of attenuated sympathetically activated thermogenesis in BAT, we assessed body temperature and the increase in mitochondrial guanosine 5'-diphosphate (GDP) binding sites in interscapular BAT in response to E. coli administration in young and senescent male F-344 rats. There was a significant delay of 2 hr in the onset of fever in the older animals. In addition, in senescent rats, the peak fever (1.0 +/- 0.1 delta degrees C vs 2.2 +/- 0.1) and the cumulative fever (383 +/- 43 delta degrees C.min vs 775 +/- 69) were significantly less than in the young rats (P less than 0.005). Baseline levels of GDP binding were the same in young and old rats. In young rats, during the rising phase of the fever, E. coli infection resulted in a 50% increase in the density of GDP binding sites in BAT mitochondria. In contrast, there was no increase in GDP binding in the older rats following infection. The failure to increase GDP binding may be a result of a reduced ability to unmask reserve GDP binding sites. Alternatively, there may be fewer total GDP binding sites (masked and unmasked) in senescent rats and these sites may already be unmasked. Collectively, these data suggest that the impaired febrile response with age is due to reduced thermogenesis in BAT.     

Energy balance and brown adipose tissue thermogenesis during chronic endotoxemia in rats

The effects of continuously administered endotoxin on 7-day energy balance were investigated in male rats. Three groups of rats were implanted with osmotic pumps; two groups received saline-filled pumps, whereas the third received endotoxin. One of the saline groups was pair fed to match the food intake of the endotoxemic rats. After 7 days, body energy and protein and fat contents of rats were determined together with the energy content of food and feces. Endotoxin infusion not only induced fever, but it also suppressed appetite and significantly decreased body weight gain. Metabolizable energy intake was reduced by approximately 20% in infected rats. Although protein and fat gains were lowest in the endotoxin group, there appeared to be a selective loss of protein when considered as percent of body weight. Percent body fat was unaltered between the groups. Energy expenditure considered in absolute (kJ) or body weight-independent (kJ/kg0.67) terms yielded similar patterns of results; expenditure (kJ) was 10 and 20% (P less than 0.05, P less than 0.01) lower in the endotoxemic and pair-fed rats, respectively, compared with controls. Hence, compared with pair-fed rats, endotoxin-infused animals had a 10% rise in their expenditure. Brown adipose tissue thermogenesis was assessed by mitochondrial binding of guanosine 5'-diphosphate, and results showed that binding was greatest in endotoxemic rats and lowest in the pair-fed animals. The present results suggest that in this endotoxemic model appetite suppression exacerbates changes in energy balance. However, the reduction in body weight gain is also dependent on a decrease in metabolic efficiency and an increase in total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma free fatty acid levels during cold-induced and noradrenaline-induced nonshivering thermogenesis in the Djungarian hamster

Summary In Djungarian hamsters the cold-induced thermoregulatory heat production was preceeded and accompanied by an increase in the plasma level of free fatty acids. In warm-acclimated hamsters this increase was found more pronounced (0.85 to 1.48 mM) than in cold-acclimated hamsters (0.64 to 0.88 mM). Noradrenaline-induced thermogenesis at thermoneutrality provoked a similar increase in the free fatty acid level. Inhibition of nonshivering thermogenesis during cold exposure by propranolol abolished the increase in free fatty acids completely. The surgical removal of brown adipose tissue proportionately reduced the increase in free fatty acids. This indicates that the rise in plasma free fatty acids is functionally related to nonshivering thermogenesis and originates from brown adipose tissue.