Effects of a high-fat diet on energy intake and expenditure in rats

The effects of a high-fat diet supplying a constant energy/protein ratio, with and without overeating, on energy intake and expenditure was studied in mature male rats. A control group (LF) received $\text{ad libitum}$ access to a low-fat diet. Body weight gain, efficiency of food utilization, and dietary-induced thermogenesis were increased relative to controls in a group with $\text{ad libitum}$ access to the high-fat diet (HF-A), but not in a group which was pair fed the diet (HF-P) in amounts (kcal) equal to that of LF animals. However, the individual variability within the HF-A group was high for each measure. An arbitrary separation of that group into 2 subgroups (based on high vs low weight gain) produced one subgroup with increased efficiency, greater weight gain and no change in dietary-induced thermogenesis (HF-AH), and another with no difference in efficiency or in weight gain from the LF group but which had higher dietary-induced thermogenesis (HF-AL). Food intake was slightly, but not significantly, greater for the HF-AH subgroup than for the HF-AL subgroup. We conclude that rats can increase thermogenesis in response to overeating but that the increase is highly variable. The thermogenic response appears to be related to the overeating rather than to the fat content of the diet.     

Opioids in the regulation of food intake and energy expenditure

This paper and the following four papers summarize a symposium on the role of opioids in regulation of feeding, body weight, and energy expenditure. The central sites of opioid action are discussed, as is opioid activity in invertebrates, large animals, and humans. This paper provides a historical review of developments in the field from the early concepts of an endogenous opioid system to the current understanding of multiple receptor types and their interaction in regulating ingestive behavior. Opioids from all three opioid families may stimulate food intake, and some evidence exists that opioids may stimulate energy expenditure. Eating and drinking behavior is very complex and involves a number of components. Our understanding of the role of opioids in this process is shallow, and future research must be designed carefully to evaluate individual components of ingestive behavior.     

Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice

Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21°C to 28°C) rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40±1%) and dark cycle energy expenditure (15±3%) at normal ambient temperature (21°C). Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65±7%), thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14±2% at 21°C; 21±4% at 28°C), while food intake was reduced during the dark cycle (0.9±0.1 g) in mice housed at 28°C, but during the light cycle (0.3±0.1 g) in mice housed at 21°C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R² = 0.51, p<0.01). We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure.     

Divergence of melanocortin pathways in the control of food intake and energy expenditure

Activation of melanocortin-4-receptors (MC4Rs) reduces body fat stores by decreasing food intake and increasing energy expenditure. MC4Rs are expressed in multiple CNS sites, any number of which could mediate these effects. To identify the functionally relevant sites of MC4R expression, we generated a loxP-modified, null Mc4r allele (loxTB Mc4r) that can be reactivated by Cre-recombinase. Mice homozygous for the loxTB Mc4r allele do not express MC4Rs and are markedly obese. Restoration of MC4R expression in the paraventricular hypothalamus (PVH) and a subpopulation of amygdala neurons, using Sim1-Cre transgenic mice, prevented 60% of the obesity. Of note, increased food intake, typical of Mc4r null mice, was completely rescued while reduced energy expenditure was unaffected. These findings demonstrate that MC4Rs in the PVH and/or the amygdala control food intake but that MC4Rs elsewhere control energy expenditure. Disassociation of food intake and energy expenditure reveals unexpected divergence in melanocortin pathways controlling energy balance.     

Effects of somatostatin on food intake in rats

We examined the possibility that somatostatin, a tetradecapeptide distributed in the gut and the central nervous system, may influence food intake and behavior in rats. Although intravenously infused somatostatin did not alter food intake in 8 hour fasted rats, intracerebroventricularly infused somatostatin resulted in a biphasic response, first increasing then decreasing food intake. We also observed that the effects of somatostatin vary depending upon whether animals are fed or fasted. In fed rats, food intake was decreased, while in fasted rats food intake was increased. These results suggest that somatostatin can act in the central nervous system to stimulate appetite; but that other factors, possibly related to gut motility or clearance, may inhibit further feeding once the stomach is full.     

Effects of urocortin 2 and 3 on motor activity and food intake in rats

Urocortin 2 (Ucn 2) and Ucn 3 are new members of the corticotropin-releasing factor (CRF) family and bind selectively to the CRF type 2 receptor (CRF2). The effects of these peptides on behavioral changes induced by CRF were examined in rats. In a familiar environment, intracerebroventricular injection of Ucn 2 attenuated the stimulatory effect of CRF on motor activity, although it alone produced no effect. Ucn 3 suppressed motor activity and attenuated the stimulatory effect of CRF. In an open field, CRF decreased locomotion and rearing but increased grooming behavior. Ucn 2 attenuated the inhibition of locomotor activity induced by CRF without affecting other activities, such as rearing or grooming behavior. Ucn 3 had no effect on the behavioral changes induced by CRF, although it alone decreased locomotion and rearing in a manner similar to CRF. Ucn 2 was thus found to have an antagonistic effect on bi-directional motor activation induced by CRF, while Ucn 3 had a suppressive effect on motor activity. Both Ucn 2 and Ucn 3 suppressed food intake in freely-fed rats, but not immediately after injection. These results suggest that the CRF2 receptor is involved in motor suppressive effects as well as anxiolytic and anorectic effects of Ucn 2 and Ucn 3.     

Effects of acute or chronic opioid agonists and their modulation by diurnal rhythmicity and satiety states on food intake in rats.

The effects of acute or chronic treatment with mu and k opioid agonists were investigated on food intake during light (0-6 hr) and dark (6-24 hr) phases in free fed and fasted rats. In free fed rats, morphine (MOR, 5 mg/kg, ip), a mu-agonist, induced a hyperphagic response during both light and dark phases, whereas ketocyclazocine (KCZ, 1 mg/kg, ip), a k-agonist, enhanced food intake only during the light phase. Chronic MOR (x 7 days) produced a further enhancement of hyperphagia in the light phase and attenuated the dark phase response. Chronic KCZ, however, had opposite effects, i.e. tolerance to light phase hyperphagia and an enhancement in the dark phase response. In fasted rats, neither MOR nor KCZ appreciably enhanced food intake after acute administration but chronic treatment potentiated the acute opioid effects. These results are discussed in light of the role of diurnal rhythmicity, satiety states and receptor (mu and k) specificity/interactions in the opioidergic regulation of food intake.     

PDK1-Foxo1 in agouti-related peptide neurons regulates energy homeostasis by modulating food intake and energy expenditure

Insulin and leptin intracellular signaling pathways converge and act synergistically on the hypothalamic phosphatidylinositol-3-OH kinase/3-phosphoinositide-dependent protein kinase 1 (PDK1). However, little is known about whether PDK1 in agouti-related peptide (AGRP) neurons contributes to energy homeostasis. We generated AGRP neuron-specific PDK1 knockout (AGRPPdk1(-/-)) mice and mice with selective expression of transactivation-defective Foxo1 (Δ256Foxo1(AGRP)Pdk1(-/-)). The AGRPPdk1(-/-) mice showed reductions in food intake, body length, and body weight. The Δ256Foxo1(AGRP)Pdk1(-/-) mice showed increased body weight, food intake, and reduced locomotor activity. After four weeks of calorie-restricted feeding, oxygen consumption and locomotor activity were elevated in AGRPPdk1(-/-) mice and reduced in Δ256Foxo1(AGRP)Pdk1(-/-) mice. In vitro, ghrelin-induced changes in [Ca(2+)](i) and inhibition of ghrelin by leptin were significantly attenuated in AGRPPdk1(-/-) neurons compared to control neurons. However, ghrelin-induced [Ca(2+)](i) changes and leptin inhibition were restored in Δ256Foxo1(AGRP)Pdk1(-/-) mice. These results suggested that PDK1 and Foxo1 signaling pathways play important roles in the control of energy homeostasis through AGRP-independent mechanisms.     

Deadenylase-dependent mRNA decay of GDF15 and FGF21 orchestrates food intake and energy expenditure

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Restriction of energy intake, energy expenditure, and aging

Energy restriction (ER), without malnutrition, increases maximum life span and retards the development of a broad array of pathophysiological changes in laboratory rodents. The mechanism responsible for the retardation of aging by ER is, however, unknown. One proposed explanation is a reduction in energy expenditure (EE). Reduced EE may increase life span by decreasing the number of oxygen molecules interacting with mitochondria, thereby lowering reactive oxygen species (ROS) production. As a step toward testing this hypothesis, it is important to determine the effect of ER on EE. Several whole-body, organ, and cellular studies have measured the influence of ER on EE. In general, whole-body studies have reported an acute decrease in mass-adjusted EE that disappears with long-term ER. Organ-specific studies have shown that decreases in EE of liver and gastrointestinal tract are primarily responsible for initial reductions in EE with ER. These data, however, do not determine whether cellular EE is altered with ER. Three major processes contributing to resting EE at the cellular level are mitochondrial proton leak, Na(+)-K(+)-ATPase activity, and protein turnover. Studies suggest that proton leak and Na(+)-K(+)-ATPase activity are decreased with ER, whereas protein turnover is either unchanged or slightly increased with ER. Thus, two of the three major processes contributing to resting EE at the cellular level may be decreased with ER. Although additional cellular measurements are needed, the current results suggest that a lowering of EE could be a mechanism for the action of ER.     

Effects of peripheral CCK receptor blockade on food intake in rats

Type A cholecystokinin receptor (CCKAR) antagonists differing in blood-brain barrier permeability were used to test the hypothesis that satiety is mediated, in part, by CCK action at CCKARs located peripheral to the blood-brain barrier. At dark onset, non-food-deprived rats received a bolus injection of devazepide (2.5 micromol/kg iv), a 3-h infusion of A-70104 (1 or 3 micromol x kg-1 x h-1 iv), or vehicle either alone or coadministered with a 3-h infusion of CCK-8 (10 nmol x kg-1 x h-1 iv) or a 2-h intragastric infusion of peptone (1 g/h). Food intake was determined from continuous computer recordings of changes in food bowl weight. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of Nalpha-3-quinolinoyl-d-Glu-N,N-dipentylamide (A-65186), does not. CCK-8 inhibited 3-h food intake by more than 50% and both A-70104 and devazepide abolished this response. A-70104 and devazepide stimulated food intake and similarly attenuated the anorexic response to intragastric infusion of peptone. Thus endogenous CCK appears to act, in part, at CCKARs peripheral to the blood-brain barrier to inhibit food intake.     

Leptin: a possible link between food intake, energy expenditure, and reproductive function

Several regulatory substances participate in the regulation of both food intake/energy metabolism and reproduction in mammals. Most of these neuropeptides originate and act in the central nervous system, mainly at specific hypothalamic areas. Leptin represents a signal integrating all these functions, but originating from the periphery (adipose tissue) and carrying information mainly to central structures. Observations in rodent models of leptin deficiency have suggested that leptin participates in the control of reproduction, in conjunction with that of food intake and energy expenditure. Indeed, leptin administration resulted in the restoration of normal body weight, food intake, and fertility in the ob mouse, lacking circulating leptin. Specific targets of leptin in the hypothalamus are neurons expressing neuropeptide Y, proopiomelanocortin and gonadotropin-releasing hormone, but the presence of leptin receptors in peripheral reproductive structures suggests that leptin might also act at these sites. Human obesity is often associated with reproductive disturbances. The situation in humans is more complex than in the animal models of leptin deficit and the presence of leptin resistance in these subjects is suggested. In conclusion, leptin fits many requirements for a molecule linking the regulation of energy balance and the control of reproduction.     

Nectar intake and energy expenditure in a flower visiting bat

Summary In a coastal region of Venezuela the daily energy expenditure (DEE) and water turnover of the flower visiting bat Anoura caudifer was measured by using the doubly labeled water method. In flower visitors, this method allows independent measurement of energy intake and expenditure if the animals drink no additional water and if the nectar's energy content is known. An average DEE of 12.4 kcal/d and water exchange of 13.4 ml/d were found. Our data show a balanced energy budget when animals in the field imbibe nectar with a sugar concentration of 18–21%, which is roughly medial in the range of nectar concentrations of various bat flowers. The energy turnover of flower visiting bats is high compared with DEEs of other bat species, small mammals and birds; flower visiting bats seem to belong to those species having a fast spin of the life motor.     

Effects of long-term food restriction on energy expenditure and thermoregulation in broiler-breeder fowls (Gallus domesticus)

• 1.1. From 2 to 21 weeks of age, 150 female broiler-breeder chicks received one of three dietary treatments. Fifty received an ad libitum supply of food (treatment AL). The remaining 100 were given weighed (restricted) rations once a day, 50 receiving the amount per bird recommended in the Ross 1 Parent Stock Management Manual (treatment R) and the other 50 receiving twice this recommended amount (treatment 2R). Water was provided ad libitum for all treatment groups.
• 2.2. The daily allowance for R birds increased from 26 g per bird at 2 weeks of age to 94 g at 21 weeks. The intake of AL birds meanwhile increased from 65 g at 2 weeks to 240 g at 19 weeks, before decreasing to about 200 g at 21 weeks.
• 3.3. Median heat productions (H) per bird in the R and 2R treatment groups were, respectively, 65 and 40% lower than in the AL when adjustment was made for the reduced food intake of AL birds in the calorimeter chambers. The effects of dietary treatment on fasting H were proportionally similar.
• 4.4. Because the increasing divergence in body weights would have made a large contribution to differences in H per bird, the results were adjusted to the median weight of 2.03 kg and to unit weight (1.00kg). Adjusted fasting heat production was 18 and 11% less in 2R and R birds than in those fed ad libitum.
• 5.5. If age was included as a variate in the logarithmic multiple regression, H was proportional to body weight (W, kg) raised to the power 0.73; if age was not included, H was proportional to W^0.55.
• 6.6. Rectal temperature was 0.7°C higher in AL birds at ambient temperatures of both 23 and 28°C. All treatment groups had a higher rectal temperature at 28°C than at 23°C, with the AL birds most affected.
• 7.7. Foot surface temperature of R birds at an ambient temperature of 23°C was 8°C lower than that of the 2R and AL groups, indicating peripheral vasoconstriction.
• 8.8. Polypnea (panting) and wing-extension occurred frequently in the AL birds, which also had a greater water intake. It was also observed that the restricted birds tended to aggregate, while the AL groups tended to space themselves evenly about the pen.
• 9.9. It was concluded that broiler breeder fowl responded to restricted food intake by a reduction in heat production over and above that resulting directly from reduced metabolism of food and reduced body weight. The reduced metabolic rate per unit of weight conferred a thermoregulatory advantage at high ambient temperature.

     

Effects of recombinant human interleukins on food intake of previously food-deprived rats

The effects of intracerebroventricular injection of recombinant human interleukin 1 beta (rhIL-1 beta), 1 alpha (rhIL-1 alpha), and 2 (rhIL-2) on feeding behavior were examined in previously food-deprived rats for 18 hr. At doses of 2-17 ng/rat, rhIL-1 beta significantly reduced food intake in a dose-dependent manner and the feeding suppression continued about 4 hr later. Only 17 ng/rat rhIL-1 beta reduced body weight gain for 8 hr after the injection. However, rhIL-1 alpha at dose of 17 ng/rat did not show any significant change of food intake and body weight gain during the whole observation period. At both doses of 8 and 40 ng/rat, rhIL-2 also failed to suppress overfeeding after food deprivation. In adrenalectomized rats, feeding suppression by rhIL-1 beta appeared at the 1- to 2-hr time period. The present studies suggest that rhIL-1 beta may be, at least in part, involved in feeding suppression on various inflammatory processes and that adrenal hormones may not play an important role in the induction of feeding suppression by rhIL-1 beta.     

Increased resting energy expenditure, fat oxidation, and food intake in patients with highly active antiretroviral therapy-associated lipodystrophy

Highly active antiretroviral therapy (HAART) is associated with metabolic adverse events such as lipodystrophy in human immunodeficiency virus (HIV)-infected patients. The objective of the present study was to evaluate the effects of HAART-associated lipodystrophy on resting energy expenditure and caloric intake. In this cross-sectional study we compared resting energy expenditure (REE) and energy intake in 30 HAART-treated patients with lipodystrophy (HAART+LD+) with 13 HAART-treated patients without lipodystrophy (HAART+LD-). REE was measured using indirect calorimetry, and energy intake was recorded as a 3-day diary of food intake. REE (5,180+/-160 vs. 4,260+/-150 J/min, P<0.01) and also REE expressed per fat-free mass (86+/-1 vs. 78+/-2 J.kg fat-free mass-1.min-1, P<0.01) were significantly higher in the HAART+LD+ than the HAART+LD- group. Rate of lipid oxidation was significantly higher in the HAART+LD+ than the HAART+LD- group. Total energy and fat intakes were significantly increased in the HAART+LD+ compared with the HAART+LD- group. These results imply that HAART-associated lipodystrophy is associated with increased REE and lipid oxidation and with increased caloric and fat intake.     

Litorin suppresses food intake in rats

Litorin (LIT), a bombesin-like nonapeptide, decreased food intake in rats in a dose-related manner after parenteral injection. LIT decreased deprivation-induced water intake only at a dose much higher than required to suppress feeding. LIT administration did not significantly alter the frequency of observed feeding-associated behaviors, nor did it result in subsequent aversion to an associated novel solution. Litorin shares with bombesin structural features and pharmacological actions that include the suppression of food intake in a manner that mimics natural satiation.     

Contrasts in energy intake and expenditure in sit-and-wait and widely foraging lizards

Summary Daily energy metabolism and water flux were measured with doubly labeled water in the free-living insectivorous lizards Cnemidophorus tigris (mean body mass 15.7 g) and Callisaurus draconoides (8.6 g) in June 1979 in the Colorado Desert of California. C. tigris was an active forager; it spent 91% of its 5-h daily activity period in movement. C. draconoides was a sit-and-wait predator; it spent less than 2% of its 10-h activity period in movement. C. tigris had significantly higher rates of field energy metabolism and water influx (210 Jg^-1 day^-1, 36.8 ul H₂O g^-1 day^-1, N=19) than C. draconoides (136, 17.1, N=18). There were no significant differences between the sexes within either species.The extra costs of free existence were calculated from differences between field metabolic rates and maintenance costs estimated from laboratory respirometry. Rates of energy metabolism during the field activity period were about 1.5x resting levels at 40° C (field active body temperature) for C. draconoides and 3.3 x resting levels at 40° C (field active body temperature) for the more active C. tigris. Feeding rates calculated from water influx data were 13.3 mg g^-1 day^-1 for C. tigris and 5.8 mg g^-1 day^-1 for C. draconoides. Though C. tigris had a high rate of energy expenditure, its foraging efficiency was higher than C. draconoides'.