Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes

The Streptozotocin (STZ) model of diabetes is commonly used for studies of diabetic nephropathy although the histological lesions of the kidney are mild and do not resemble those seen in diabetic patients. The SHR/N-cp rat model of type II diabetes spontaneously develops pronounced abnormalities in renal histology. In the present study, we compared renal morphology in the STZ rat and the diabetic SHR/N-cp rat. Sprague-Dawley rats received STZ, developed diabetes after 2 days and were treated with insulin. In the SHR/N-cp rat, obesity is inherited as an autosomal recessive trait. The progeny are either lean (used as controls) or obese and diabetic. After 6 months of observation, STZ and SHR/N-cp rats were killed. The renal damage was evaluated by assessing damage indices and by using stereological techniques. In addition, immunohistochemistry and electron microscopy were performed. The glomerular and tubulointerstitial changes were much more pronounced in the diabetic SHR/N-cp compared to the STZ model. In parallel glomerular PCNA+cells were significantly more frequent and expression of TGF-beta and PDGF by immunohistochemistry in glomeruli and in the tubulointerstitial space was more pronounced in SHR/N-cp compared to STZ rats. The glomeruli of SHR/N-cp contained less and larger podocytes as well as smaller mesangial cells embedded in more mesangial matrix compared to STZ. Similarly, less, but larger endothelial cells were found in SHR/N-cp than in STZ rats. The mean glomerular volume was similarly increased in the two models. Albumin excretion was only modestly increased in STZ diabetes, but pronounced in the SHR/N-cp rat. Although the STZ model of diabetes exhibits numerous biochemical sequelae of hyperglycemia, the morphological lesions are unimpressive. In contrast, the diabetic SHR/N-cp exhibits marked structural lesions, particularly podocyte damage and mesangial expansion that promise to make it a more suitable model for investigation of diabetic glomerulosclerosis.     

Renal damage in the SHR/N-cp type 2 diabetes model: comparison of an angiotensin-converting enzyme inhibitor and endothelin receptor blocker

SUMMARY: The pathomechanisms that cause renal damage in diabetes have not been completely clarified. Treatment with angiotensin-converting enzyme inhibitors (ACE-i) is highly effective but fails to completely prevent end-stage renal disease. The effects of ET(A)-receptor blockers (ET(A)-RB) on renal damage are controversial and have rarely been investigated in type 2 diabetes. We compared the influence of the selective ET(A)-RB LU135252 and the ACE-i Trandolapril on renal structure in the SHR/N-cp rat model of type 2 diabetes. Three-month-old male SHR/N-cp rats were left untreated or received daily either Trandolapril or LU135252. The experiment was terminated after 6 months. The glomerulosclerosis index; tubulointerstitial damage index; and glomerular geometry, glomerular cell number, and capillary density were investigated. Proliferating cell nuclear antigen and desmin expression of podocytes, renal mRNA expression of endothelin (ET-1) and transforming growth factor-beta, blood pressure, and urine albumin excretion were measured. The glomerulosclerosis index was significantly higher in untreated diabetic animals than in the groups that were treated with ACE-i and ET(A)-RB. There were analogous changes in tubulointerstitial damage index. Treatment with either substance comparably lowered urinary albumin excretion in diabetic SHR/N-cp. Podocyte and endothelial cell numbers per glomerulus decreased in untreated diabetic animals; this was prevented by the ACE-i but not by the ET(A)-RB. Glomerular capillary length density was lower in SHR/N-cp, and this was normalized by ACE-i only. Increased expression of desmin and proliferating cell nuclear antigen expression of podocytes in the SHR/N-cp was abrogated by ACE-i but not by ET(A)-RB. Treatment with ACE-i or ET(A)-receptor antagonist resulted in less structural and functional alterations, but the ET(A)-RB was inferior to the ACE-i. This is particularly the case for podocyte changes pointing to angiotensin II-dependent pathomechanisms.     

Effects of dietary protein on food and water intake in spontaneously hypertensive rats

We have been studying the development of hypertension in spontaneously hypertensive rats (SHR) fed a low protein diet. The effects of a low protein diet upon food and water intake were examined. Body weight gain, food and water intake were measured in three to twenty-three week-old SHR and Wistar Kyoto rats (WKY) fed diets containing 8%, 15% or 25% casein. Body weights of SHR and WKY fed an 8% casein diet were significantly lower at 23 weeks than rats on the higher protein diets, although both groups on the 8% diet consumed more food and water per g of body weight. In addition, SHR fed an 8% casein diet drank less water per gram of food than WKY or SHR fed 15% and 25% casein diets. These results indicate that changes in food and water intake, as a consequence of low protein diets, should be an additional consideration when examining the effects of dietary protein on the development of hypertension.     

Differential effects of quinine and sucrose octa acetate on food intake in the rat

Twenty-seven adult female rats were fed chow diets containing quinine sulfate, sucrose octa acetate, or alphacel. Quinine produced a greater, more prolonged depression of food intake than did SOA. Quinine also resulted in loss of body weight.     

Traits of the metabolic syndrome alter corpulent obesity in LAN, SHR and DSS rats: behavioral and metabolic interactions with adrenalectomy

Obesity results from a complex interaction of genes with environmental factors. Our experimental design compared obesity in three rat strains with the corpulent (cp) mutation. The three strains included Lister and Albany NIH (LAN) rats, Spontaneously Hypertensive Rats (SHR) and Dahl Salt Sensitive (DSS) rats that were congenically bred. The strains were selected because of different reported metabolic complications generally clustered with obesity, and defined as the metabolic syndrome. Body weight, food intake, carcass composition, plasma hormones and hypothalamic expression of Y5 receptors were assessed in obese (cp) and lean (wt) rats after adrenalectomy (ADX) or sham surgeries. Plasma corticosterone in sham-operated wtDSS and cpDSS were significantly higher (approx. 165 ng/ml) than that in cpLAN and cpSHR (~ 77 and 68 ng/ml respectively). All cp groups had a higher % carcass fat than wt groups. The % carcass fat was greater in cpDSS > cpLAN > cpSHR but plasma leptin was greatest in cpLAN > cpSHR > cpDSS. Hypothalamic expression of the Y5R after ADX resulted in a phenotype × surgery interaction since Y5R expression was slightly increased in cp rats and slightly decreased in wt rats. The strain with greatest number of metabolic syndrome traits, SHR, was not the fattest of the strains and had little response to ADX. The strains with fewer metabolic syndrome traits LAN and DSS had more extreme obesities which were attenuated after ADX. The results of the current experiment provide evidence that the corpulent mutation is not fully characterized in one strain.     

Diet modification and its influence on metabolic and related pathological alterations in the SHR/NDmcr-cp rat,an animal model of the metabolic syndrome

SHR/NDmcr-cp (SHR/NDcp) rats, which carry a nonsense mutation of the leptin receptor gene, are known to spontaneously develop hypertension, obesity and hyperlipidemia, and have therefore found use as an animal model of the metabolic syndrome and type 2 diabetes. However, some recent studies on SHR/NDcp rats revealed only mild elevation of blood glucose levels. To investigate whether metabolic factors including blood glucose and histopathological alterations of SHR/NDcp rats deteriorate with a diabetogenic diet, biochemical and histopathological examinations were conducted with animals fed normal or diabetogenic diets for 20 weeks. SHR/NDcp rats receiving the normal diet displayed obesity, hypertension, hyperlipidemia, and mild elevation of blood glucose and HbA1c levels. Urinary glucose excretion was noted in only 1 out of 6 animals. Histologically, macro- and micro-vesicular steatosis in the liver, glomerular and tubular damages in the kidney and islet hyperplasia mainly of beta cells in the pancreas were characteristically noted. In SHR/NDcp rats fed the diabetogenic diet, obesity was more severe, with higher blood glucose and HbA1c levels, increased numbers of animals with urinary glucose excretion, and more pronounced hepatic steatosis and renal tubular changes. However, elevation of blood glucose levels and urinary glucose excretion proved transient. These observations indicate that the diabetic state and associated histopathological alterations in SHR/NDcp rats are exacerbated by feeding a diabetogenic diet, but the effects are limited. Elevated islet function with compensative insulin secretion might be related to amelioration of the hyperglycemic state. Further diet modification could be needed to induce a more prominent and persistent diabetic state in SHR/NDcp rats.     

Modulation of adrenergic receptors and adrenergic functions in cold adapted humans

To specify the role of adrenoceptors in mediating adrenergic functions after adaptation of humans to cold, effect of administration of increasing concentrations of beta1 and beta2 adrenomimetics (Dobutamine, Bricanyl) on resting metabolic rate, heart rate, systolic blood pressure, rectal and skin temperatures of control humans and of cold adapted winter swimmers was studied. Increase in metabolic rate, mediated by beta1 and beta2 adrenomimetics, was attenuated after cold adaptation, indicating downregulation of beta1 and beta2 adrenoceptors. Since cold adapted humans have greater capacity of nonshivering thermogenesis, than that mediated by both beta1 and beta2 adrenoceptors, the role of other subtypes of adrenoceptors in mediating nonshivering thermogenesis is anticipated. Heart rate increased after administration of the beta2 agonist, but was not influenced by the beta1 agonist. The significance of beta2 adrenoceptors in mediating heart rate was depressed after cold adaptation. Data indicate that modifications of activity of beta adrenoceptors play crucial role in mechanisms responsible for adaptation of humans to cold.     

Sympatho-adrenal hyperreactivity to footshock stress but not to cold exposure in spontaneously hypertensive rats

No significant differences in plasma levels of catecholamines were found in blood obtained via an indwelling tail artery catheter from awake, undisturbed spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) or NIH Sprague-Dawley rats. Although the blood pressures of SHR rats increased between 4 and 10 months of age, there were no changes in basal plasma catecholamine levels. Exposure to cold for 20 or 240 min resulted in significant increments in plasma catecholamine levels which were similar in SHR and WKY rats. In contrast, exposure to 5 min of inescapable footshock (2.5 mA, 0.4 sec duration, every 5 sec) produced striking increments in plasma catecholamines that were greater in SHR rats than in normotensive WKY or NIH Sprague-Dawley rats. SHR rats also exhibited greater levels of plasma corticosterone than WKY rats at 15 min after termination of footshock. Our results demonstrate that SHR rats are hyperadrenergic in their responses to some but not all forms of stressful stimulation.     

Effect of sport-drink with and without fluoride and magnesium supplements on rat performance

Summary Young Osborne-Mendel rats were given different diets ad libitum for 6 weeks. Food was either a purified powder with sucrose (15%) or commercial pellets, and drink was either distilled water or a sugar-containing (6%) sport-drink with or without added fluoride (F), magnesium (Mg) or both. Despite differences in the energy density of the diets, daily intakes were the same in terms of metabolisable energy and resulted in equal weight gains for all groups. Interscapular brown fat hypertrophied in response to powdered food, while both sugar-containing food and sport-drink were effective in accumulating white fat. When exposed to cold air at –20° C for 2–4 h, most of the rats were able to maintain normothermia. Only the rats fed pelleted food and given distilled water were less resistant to cold than the others. After exposure to cold, the reserves of muscle glycogen were least in those rats having the poorest performance in the cold. In contrast, the stores of liver glycogen, plasma glucose and adrenal ascorbic acid were associated with pelleted food, rather than with the exposure to cold or type of drink. It is concluded that the presence of purified, simple sugars, either in food or drink, is the most likely explanation of the results obtained. The F and Mg supplements to the sport-drink did not modify the parameters measured.     

Inhibition of diet-induced thermogenesis during pregnancy in the rat

Both virgin and pregnant rats were maintained at two different ambient temperatures (28° C and 10° C) for 19 days. Virgin rats maintained their daily food intake and body weight at both temperatures. At 28° C pregnant rats showed a greater daily food intake and body weight than virgin ones and their brown adipose tissue suffered regressive changes in composition when compared with brown fat of virgin rats. At 10° C the increases in daily food intake and body weight of pregnant rats took place from day 15–16 of pregnancy onward and foetuses taken from these pregnant rats were smaller than those taken from pregnant rats at 28° C. It is concluded that pregnant rats at thermoneutrality, although hyperphagic, do not show diet-induced thermogenesis. However, it is proposed that pregnant rats in the cold may show BAT cold-induced thermogenesis.     

Thermoregulation in winter swimmers and physiological significance of human catecholamine thermogenesis

Thermoregulation in control subjects and cold-adapted winter swimmers was examined during 1 h of cold water immersion (13 C). It was found that the thermoregulatory functions of winter swimmers differ from those of non-cold-adapted subjects. As evident from the relationship between rectal temperature and the magnitude of cold thermogenesis, in controls a significant part of cold thermogenesis during the early phase of cooling was induced by changes in peripheral temperature input, while in the late phase of cooling it was the central temperature input which was mainly engaged in induction of cold thermogenesis. In winter swimmers the magnitude of cold thermogenesis was solely related to changes in rectal temperature, indicating the predominance of the central temperature input in activation of heat production mechanisms. The thermoregulatory threshold for induction of cold thermogenesis was lowered (by 0.34 C), but the apparent hypothalamic thermosensitivity was the same as in non-cold-adapted subjects. These differences are indicative of adaptation of thermoregulatory control centres. Additionally, the activity of thermoregulatory effectors was also changed. Shivering was induced later during cooling (after 40 min) in winter swimmers than in controls, which suggests an important participation of non-shivering thermogenesis in the early thermogenic response. Winter swimmers also showed bradycardia and a greater reduction in plasma volume during cooling. The data indirectly indicate restriction of heat loss from the body. Only a non-significant increase in quantity of subcutaneous fat was observed in winter swimmers. Thus, winter swimmers were able to survive a significantly greater temperature gradient between body and environment than non-cold-adapted subjects by modifying the sensory functions of hypothalamic thermoregulatory centres to lower heat loss and produce less heat during cold exposure. Additionally, the capacity of the total cold thermogenesis due to potentiation of non-shivering heat production was also increased. Heat produced due to thermogenic action of adrenaline may represent more than a quarter of the total cold thermogenesis. In conclusion, the data suggest that winter swimmers exhibit metabolic, hypothermic and insulative types of cold adaptation.     

Myocardial disease and catecholamine metabolism in JCR:LA-corpulent rat

The JCR:LA-cp rat is a strain carrying the mutant cp (corpulent) gene. Animals that are homozygous cp are hyperphagous, hyperinsulinemic, hyperlipidemic, and obese. Corpulent male rats, but not females or lean rats, develop atherosclerotic lesions and myocardial lesions. Since the myocardial lesions are apparently of ischemic origin, the noradrenergic system and vascular hyperactivity and vasospasm may play a role in the pathogenesis. To test this we have studied the brain contents of the amines norepinephrine, dopamine, and 5-hydroxtryptamine and their breakdown products and depleted the peripheral sympathetic terminals with 6-hydroxydopamine. Only 5-hydroxytryptamine and 5 hydroxyindole-3-acetic acid were present at higher concentrations in the corpulent rats with depressed levels of dopamine in very young or old lean rats. The activity of monoamine oxidase may provide an indication of nonadrenergic activity in tissue. The activity in the heart increased with age and was higher in the corpulent rats than in the lean at all ages. Activity in aorta was independent of age or genotype. Long term treatment with 6-hydroxydopamine caused marked depletion of norepinephrine in the heart with only a slight decrease in brain concentration. There were no effects on the hyperlipidemia or hyperinsulinemia that are strongly associated with vascular and myocardial disease. The myocardial lesion frequency in corpulent rats was not altered by the chemical sympathectomy. The results suggest that norepinephrine and the sympathetic nervous system are probably not involved in the generation of the myocardial lesions or metabolic abnormalities in this strain of rat.     

Overeating, overweight and obesity induced by an unpreferred diet

Rats fed diets containing 50-71% added water (liquid diets) eat more energy and gain more weight than rats fed the same diets without added water (solid diets). The present experiments examined the effects of making a liquid diet less palatable. The first experiment examined the effects of sucrose octaacetate on diet preference. Rats, given a choice of a liquid diet containing 0.5% sucrose octaacetate and a plain solid diet, preferred the plain solid diet for three weeks. When the concentration of sucrose octaacetate was reduced to 0.05%, the rats did not show a reliable preference for either the sucrose octaacetate liquid or plain dry diet. In subsequent experiments, each rat was given only one diet at a time. In the second experiment, rats were fed 0.5% sucrose octaacetate liquid diet for three weeks followed by 0.05% sucrose octaacetate liquid diet for another four weeks. The rats fed the sucrose octaacetate liquid diet overate and became obese compared to the rats fed plain solid diet throughout. In the third experiment, rats fed 0.5% sucrose octaacetate liquid diet for six weeks became obese compared to rats fed plain solid diet throughout. Thus, the overeating and obesity induced by liquid diets cannot be attributed solely to their high palatability.     

Renal function and sympathetic activity during mental stress in normotensive and spontaneously hypertensive rats

The aim of the present study was to explore the role of the renal sympathetic nerves in the urinary sodium excretion response to ‘mental stress’ in spontaneously hypertensive rats (SHR). In conscious male SHR and male Wistar Kyoto rats (WKY) urinary sodium excretion and renal function were measured both during ‘rest’ and during a 20 min period of ‘mental stress’. Experiments were also performed on renal denervated rats. In addition, renal sympathetic activity was measured in a separate group of rats. Urinary sodium excretion, similar at rest in SHR and WKY, decreased significantly more during the stress period in SHR (-64±5%) than in WKY (-34±7%), despite a greater arterial pressure increase in SHR. Renal sympathetic nerve activity which already at rest was higher in SHR than in WKY, also increased much more in SHR during stress than in WKY. The more intense renal sympathetic activation during stress may explain the greater reduction in urinary sodium excretion in SHR, because renal denervation almost abolished this latter response. Thus, during ‘mental stress’ the increased renal sympathetic activity reduces urinary sodium excretion in SHR despite the pressure rise, perhaps explaining why renal denervation delays the rise in arterial pressure in young SHR. The tachycardia response in SHR gradually subsided towards the end of the stress period, while renal sympathetic activity remained elevated. This indicates that neurogenic heart rate increases if anything underestimate the extent of sympathetic activation to e. g. the renal and splanchnic regions during increased alertness.     

Lasting effect of infantile cold experience on cold tolerance in adult rats.

The effect of short and repetitive exposure to cold (5 degrees C, 4 hr/day for 2 weeks) from the birth up to the 14th day of newborn rats onthe thermal regulation in adulthood and on the tolerance to cold was investigated. After being exposed to cold, they were transferred to a room at 25 degrees C (N-CA). The control rats were raised at 25 degrees C (N-WA). An acute cold exposure test was performed by placing the animals in a room at 5 degrees C under urethane anesthesia. Electrical activity of neck muscles as an index of shivering was recorded. The colonic temperature fell at a significantly slower rate in N-CA rats with less shivering than in N-WA ones. Nonshivering thermogenesis tested by norepinephrine was significantly greater in N-CA rats than in N-WA ones. These results suggest that N-CA rats developed improved cold tolerance accompanied by greater nonshivering thermogenesis. Such a phenomenon in N-CA lasted for 18 weeks after the termination of cold exposure. Adult rats subjected to the same scheme of cold exposure (A-CA) (5 degrees C, 4 hr/day, 2 weeks) showed essentially the same results as seen in N-CA, but its improved cold tolerance and elevated nonshivering thermogenesis disappeared 4 weeks after the termination of cold exposure. Extirpation of interscapular brown adipose tissue immediately before the cold test did not appreciably affect the cold tolerance in N-CA and A-CA rats. The colonic temperature at the onset of shivering was significantly lower in N-CA as well as A-CA rats than in each of the corresponding control rats, indicating a shift of the shivering threshold to lower temperature values in the animals exposed intermittently to cold. These results indicate that an infantile experience with cold results in a greater and longer sustained ability to tolerate cold in adulthood, characterized by enhanced nonshivering thermogenesis.     

Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.     

Thermoregulation and non-shivering thermogenesis in the genetically obese (ob/ob) mouse

1. The capacity ofr thermoregulation and thermogenesis in lean and genetically obese (ob/ob) mice has been investigated. 2. At 4 degrees C ob/ob mice rapidly die of hypothermia, because of a reduced capacity for cold-induced thermogenesis, but the animals are able to survive if previously adapted to 12 degrees C. 3. At all environmental temperatures between 30 degrees C and 10 degrees C the body temperature of ob/ob mice is 2.0-2.5 degrees C below that of lean animals. This may be due to a lower "setting" for body temperature. 4. At 34 degrees C the oxygen consumption of obese mice is greater than that of the lean animals while at 30 degrees C it is similar. When the environmental temperature is below 30 degrees C the oxygen consumption of the lean mice is greater. The obese animals therefore expend less energy on thermoregulatory thermogenesis. 5. The capacity for non-shivering thermogenesis was measured in lean and obese mice by investigating the effect of an injection of L-nor-adrenaline (1000 microgram/kg body weight) on the metabolic rate at 31 degrees C. Non-shivering thermogenesis was reduced by one-half in the obese animals. 6. One cause of the obesity of the ob/ob mouse is its high metabolic efficiency. We suggest that this high metabolic efficiency is due, at least in part, to less energy being expended on thermoregulatory thermogenesis.     

Role of sympathetic nervous system in immobilization- and cold-induced brown adipose tissue thermogenesis in rats

The role of the sympathetic nervous system in 10-min cold (5 degrees C)- or 2-min immobilization-induced thermogenesis in brown adipose tissue (BAT) was studied in warm (25 degrees C)-acclimated rats. Both cold- and immobilization-stresses increased heat production (M), interscapular brown adipose tissue temperature ( Tbat ), and colonic temperature ( Tcol ). Resulting from both stresses, the increase in Tbat was greater than that in Tcol , the differences (delta Tbat ) becoming approximately 0.48 and 0.46 degrees C by the cold exposure and the immobilization, respectively. After sympathectomy, Tbat and delta Tbat did not change on immobilization but increased significantly on the cold exposure. Delta Tbat was 0.31 degrees C in the sympathectomized rats at the end of the cold exposure period. Immobilization-induced BAT thermogenesis may be mainly controlled by the sympathetic nervous system. On the other hand cold-induced BAT thermogenesis seems to be controlled by certain hormonal factors as well as the sympathetic nervous system.     

Sodium balance during development of hypertension in the spontaneously hypertensive rat (SHR)

Sodium balance was studied in 7 and 16 week old male spontaneously hypertensive rats (SHR), in matched normotensive Wistar rats (NCR) and in Wistar Kyoto rats (WKR). The animals were placed in metabolic cages and given diets with either normal sodium content (5.35 mmol sodium/100 g food) or with a sodium content 3 or 10 times the normal. Whether on normal or increased sodium diet we did not observe any increased sodium retention in either SHR age group. However, in both SHR groups urinary sodium excretion was significantly decreased, while faecal sodium excretion was correspondingly increased compared with the controls. This shift of sodium excretion from kidneys to gastrointestinal tract in SHR did not reflect any ‘primary’ inability of the SHR kidneys to excrete sufficient sodium amounts since on high sodium diet they excreted the increased sodium load as readily as the normotensive controls. The present results do not support the concept that a primary renal retention of sodium and water should be of pathogenetic importance for the SHR variant of primary hypertension.     

Behavioural energy regulation in lean and genetically obese (ob/ob) mice

The role of behaviour in the control of energy regulation has been investigated in relation to environmental temperature, nutrition and genetics. Techniques of operant conditioning were used, with lean and genetically obese (ob/ob) mice being tested at three environmental temperatures (10, 20 and 30 degrees C) and on two feeding regimes (after a 24 hr fast and after feeding ad lib). They were allowed access to heat and food, although the design of the apparatus ensured that both were not available simultaneously. Both the lean and ob/ob showed an initial preference for heat when tested in a cold environment. At a low ambient temperature the ob/ob were dependent on the heater rather than food to increase rectal temperature, both when fasted and when fed. By contrast, the lean had a lower demand for heat than the obese and used the time to explore the environment and to feed. Food intake increased with an increase in ambient temperature in both genotypes. Possible reasons for this are discussed.