Effect of environmental temperature on dietary obesity in Osborne-Mendel rats

The effects of cold acclimation on cellularity, lipoprotein lipase (LPL) activity and lipolysis were studied in white adipose tissue of rats fed a high fat diet. Male Osborne-Mendel rats (7 weeks old) were exposed at either 28 or 5 degrees C for 10 weeks. The rats were fed a semipurified diet (normal fat (NL): 5% lard, high fat (HL): 54% lard) for the last 9 weeks. Caloric intake with NL and HL diets were comparable and cold exposure led to the same increase with both diets. At 28 degrees C, HL diet initiated both hypertrophy and hyperplasia; however, at 5 degrees C only hyperplasia was observed. Total LPL activity showed high stimulation both in 28 and 5 degrees C HL rats. In vitro lipolytic stimulation by norepinephrine was lowered at 5 degrees C and abolished at 28 degrees C in HL-fed rats. HL diet resulted in enhanced lipid deposition without an increase in caloric intake. Even in cold-adapted Osborne-Mendel rats a relative obesity could be produced by a HL diet.     

The impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in brown- and a range of white-adipose-tissue depots in vivo.

OBJECTIVE: To determine: (a) whether active pyruvate dehydrogenase (PDHa) activity in interscapular brown adipose tissue (IBAT) is acutely regulated by altered insulin status at euglycaemia; (b) the relationship between glucose uptake/phosphorylation and PDHa activities in IBAT in vivo; and (c) the impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in IBAT in comparison with that exerted on various white adipose tissue depots. DESIGN: Rats were provided with either a standard diet (8% fat, 72% carbohydrate, by energy) or a diet moderately high in saturated fat (47%, by energy) and low in carbohydrate (33%, by energy) for four weeks. Rats were studied in the absorptive state, in the post-absorptive state or after 2.5 h euglycaemic hyperinsulinaemia. Tissues sampled included IBAT and four white adipose tissue depots, two abdominal (parametrial (PM) and perirenal (PR)) and two superficial (subcutaneous (SC) and interscapular (IS)). MEASUREMENTS: Whole-body glucose disposal was estimated using [3-3H]glucose. Glucose uptake/phosphorylation in vivo was estimated using 2-deoxy[1-3H]-D-glucose. Insulin action was evaluated using the euglycaemic-hyperinsulinaemic clamp technique. PDHa activity was assayed spectrophotometrically in freeze-clamped tissue extracts. PDH kinase (PDK) activities were assayed in mitochondrial extracts by rates of ATP-dependent PDHa inactivation. RESULTS: Whole-body glucose disposal was decreased by high-fat-feeding in the post-absorptive state (P < 0.05) and during euglycaemic hyperinsulinaemia (P < 0.01). Glucose transport/phosphorylation in IBAT was decreased by high-fat feeding in the absorptive (P < 0.001) and post-absorptive states (by 84%, P < 0.05) and during steady-state euglycaemic hyperinsulinaemia (by 73%, P < 0.001). IBAT PDHa activities were suppressed by high-fat feeding. Euglycaemic hyperinsulinaemia in post-absorptive control rats increased PDHa activities in IBAT (P < 0.001) to values comparable to those found in the absorptive state. Although IBAT PDHa activities were increased by euglycaemic hyperinsulinaemia in post-absorptive high-fat-fed rats, they remained lower (by 55%; P < 0.01) than those of controls. The failure of hyperinsulinaemia to normalise IBAT pyruvate dehydrogenase complex (PDHC) activities in high-fat-fed rats was associated with a stable 1.4-fold increase in IBAT PDK activity. High-fat feeding decreased glucose utilisation rates in the post-absorptive state in IS, but not in SC, PM or PR white adipose tissue depots. Euglycaemic hyperinsulinaemia significantly increased glucose utilisation in three out of the four depots of the control rats, but did not elicit statistically-significant changes in high-fat-fed rats. High-fat feeding influenced PDHa activity in PR, but was without significant effect on PDHa activity in PM, SC and IS. CONCLUSIONS: The results demonstrate that PDHa activity in the IBAT of rats maintained on standard diet responds to changes in insulin concentrations over the low physiological range, and that inactivation of PDHa in IBAT after feeding a diet moderately high in saturated fat is a consequence of the induction of tissue insulin resistance. Effects of this dietary regime on PDHa activity are paralleled by changes in insulin-stimulated glucose uptake/phosphorylation by IBAT in vivo, and IBAT is specifically targeted, with only moderate effects in white adipose tissue. The finding of impaired activation of BAT glucose transport/phosphorylation and PDHa activity in response to insulin may contribute to impaired thermogenesis in rats maintained on diets containing a relatively high proportion of saturated fat.     

Impaired starvation-induced loss of mitochondrial protein in the brown adipose tissue of dietary obese rats.

The effects of fasting and refeeding on interscapular brown adipose tissue (IBAT) in normal rats and in those made obese by cafeteria feeding was investigated in order to evaluate the sequential feeding responses relating to the IBAT facultative thermogenesis. The thermogenic activity (GDP binding) and related parameters such as IBAT mass, tissue protein, mitochondrial protein and cytochrome c oxidase (COX) activity were compared in fed, fasted and refed situations in controls and in rats made obese by cafeteria feeding. The IBAT mass, tissue protein content, mitochondrial protein content, total COX activity and specific GDP binding were significantly increased by the cafeteria diet. The thermogenic response to fasting and refeeding was different between control and cafeteria obese rats. Thus, in control rats, the loss of mitochondrial protein as well as total COX activity are probably the main responses to fasting, whereas in cafeteria obese rats no changes in mitochondrial protein and total COX activity occur during fasting. Furthermore mitochondrial protein and total COX activity were not recovered during refeeding in control rats, and no changes occurred in cafeteria fed rats. However, the proton conductance pathway (measured by GDP binding) is inactivated in control and cafeteria fed rats on fasting. In conclusion, these results indicate different responses during fasting in the mitochondrial protein between control and dietary obese rats, suggesting a possible activated mitochondrial proteolysis in the control rats only.     

Opposite effects of feeding a vitamin A-deficient diet and retinoic acid treatment on brown adipose tissue uncoupling protein 1 (UCP1), UCP2 and leptin expression

The relationship between interscapular brown adipose tissue (IBAT) thermogenic potential and vitamin A status was investigated by studying the effects of feeding a vitamin A-deficient diet and all-trans retinoic acid (tRA) treatment on body weight and IBAT parameters in mice. Feeding a vitamin A-deficient diet tended to trigger opposite effects to those of tRA treatment, namely increased body weight, IBAT weight, adiposity and leptin mRNA expression, and reduced IBAT thermogenic potential in terms of uncoupling protein 1 (UCP1) mRNA and UCP2 mRNA expression. The results emphasize the importance of retinoids as physiological regulators of brown adipose tissue.     

Effects of dietary carbohydrate, fat, and protein on norepinephrine turnover in rats

To investigate effects of diet composition on rates of norepinephrine (NE) turnover in sympathetically innervated organs, weaning rats were fed for 2 to 21/2 weeks diets varying in carbohydrate (74.2% to 7.4% of total metabolizable energy) and fat (5.2% to 72.0%), or diets varying in protein (9.9% to 39.6%) and carbohydrate (77.8% to 48.1%). Changing the proportions of carbohydrate and fat in the diet, while maintaining similar intakes of energy and all other essential nutrients did not affect rates of NE turnover in heart, white adipose tissue (WAT), liver or pancreas and only minimally affected NE turnover in interscapular brown adipose tissue (IBAT). Decreasing the proportion of protein in the diet from 39.6% to 9.9% accelerated rats of NE turnover in heart (52%), IBAT (20%), WAT (42%), and liver (37%). When rats fed a diet containing 19.8% protein were also given a 10%(wt/vol) sucrose solution to drink for three days, their rates of NE turnover increased in heart (45%), IBAT (17%), liver (71%), and pancreas (55%). This response to sucrose depended on the protein content of the diet, since rats fed a 9.9% protein diet in which rates of NE turnover was already accelerated had no further increase in NE turnover when given the sucrose solution to drink. These data demonstrate that diet composition can affect activity of the sympathetic nervous system, as indicated by changes in rates of NE turnover. Changing the proportion of protein in the diet was more effective in altering NE turnover than changing the proportion of carbohydrate or fat.     

The effects of dietary fatty acid composition in the post-sucking period on metabolic alterations in adulthood: can ω3 polyunsaturated fatty acids prevent adverse programming outcomes?

Early life nutrition is important in the regulation of metabolism in adulthood. We studied the effects of different fatty acid composition diets on adiposity measures, glucose tolerance, and peripheral glucocorticoid (GC) metabolism in overfed neonatal rats. Rat litters were adjusted to a litter size of three (small litters (SLs)) or ten (normal litters (NLs)) on postnatal day 3 to induce overfeeding or normal feeding respectively. After weaning, SL and NL rats were fed a ω6 polyunsaturated fatty acid (PUFA) diet (14% calories as fat, soybean oil) or high-saturated fatty acid (high-fat; 31% calories as fat, lard) diet until postnatal week 16 respectively. SL rats were also divided into the third group fed a ω3 PUFA diet (14% calories as fat, fish oil). A high-fat diet induced earlier and/or more pronounced weight gain, hyperphagia, glucose intolerance, and hyperlipidemia in SL rats compared with NL rats. In addition, a high-fat diet increased 11β-hsd1 (Hsd11b1) mRNA expression and activity in the retroperitoneal adipose tissue of both litter groups compared with standard chow counterparts, whereas high-fat feeding increased hepatic 11β-hsd1 mRNA expression and activity only in SL rats. SL and a high-fat diet exhibited significant interactions in both retroperitoneal adipose tissue and hepatic 11β-HSD1 activity. Dietary ω3 PUFA offered protection against glucose intolerance and elevated GC exposure in the retroperitoneal adipose tissue and liver of SL rats. Taken together, the results suggest that dietary fatty acid composition in the post-sucking period may interact with neonatal feeding and codetermine metabolic alterations in adulthood.     

Gender differences in the dietary lard-induced increase in blood pressure in rats

We investigated the difference between male and female rats in the increase in blood pressure (BP) when they were fed a lard-enriched diet. We also investigated the effect of a gonadectomy, with or without testosterone treatment, on the dietary lard-induced increase in BP. Wistar-strain male or female rats were bilaterally castrated or ovariectomized. Some of them were implanted subcutaneously with silicon tubes containing crystalline testosterone. Each group was fed either chow alone or chow in which 50% of the energy content was from substituted lard. Systolic blood pressure (SBP) was determined weekly during each 7- or 11-week feeding period. A steady-state plasma glucose method was used to determine the insulin sensitivity. The dietary lard-induced increase in SBP was observed at 5 weeks after the start of the feeding in the sham-operated male rats. In the sham-operated female rats, SBP did not change from the basal values until 11 weeks into the experimental period. Castration eliminated the dietary lard-induced increase in SBP. Ovariectomy had no effect on SBP throughout the experimental period in both diet groups. In castrated males given testosterone, SBP increased in a dose-dependent manner. In ovariectomized females given testosterone, SBP increased significantly in the lard-enriched diet group. The dietary lard developed an insulin resistance in both the sham-operated and gonadectomized rats. However, SBP increased only in the sham-operated male rats. These results suggest that the dietary lard-induced increase in SBP depends on the presence of testosterone. The development of insulin resistance by dietary lard triggers the increase in SBP.     

Dietary supplementation of tetradecylthioacetic acid increases feed intake but reduces body weight gain and adipose depot sizes in rats fed on high-fat diets

Aim: The pan-peroxisome proliferator-activated receptor (PPAR) ligand and fatty acid analogue tetradecylthioacetic acid (TTA) may reduce plasma lipids and enhance hepatic lipid metabolism, as well as reduce adipose tissue sizes in rats fed on high-fat diets. This study further explores the effects of TTA on weight gain, feed intake and adipose tissue functions in rats that are fed a high-fat diet for 7 weeks.
Methods: The effects on feed intake and body weight during 7 weeks' dietary supplement with TTA (∼200 mg/kg bw) were studied in male Wistar rats fed on a lard-based diet containing ∼40% energy from fat. Adipose tissue mass, body composition and expression of relevant genes in fat depots and liver were measured at the end of the feeding.
Results: Despite higher feed intake during the final 2 weeks of the study, rats fed on TTA gained less body weight than lard-fed rats and had markedly decreased subcutaneous, epididymal, perirenal and mesenteric adipose depots. The effects of TTA feeding with reduced body weight gain and energy efficiency (weight gain/feed intake) started between day 10 and 13. Body contents of fat, protein and water were reduced after feeding lard plus TTA, with a stronger decrease in fat relative to protein. Plasma lipids, including Non-Esterified Fatty Acids (NEFA), were significantly reduced, whereas fatty acid β-oxidation in liver and heart was enhanced in lard plus TTA-fed rats. Hepatic UCP3 was expressed ectopically both at protein and mRNA level (>1900-fold), whereas Ucp1 mRNA was increased ∼30-fold in epididymal and ∼90-fold in mesenteric fat after lard plus TTA feeding.
Conclusion: Our data support the hypothesis that TTA feeding may increase hepatic fatty acid β-oxidation, and thereby reduce the size of adipose tissues. The functional importance of ectopic hepatic UCP3 is unknown, but might be associated with enhanced energy expenditure and thus the reduced feed efficiency.     

Lipolytic activities in rats fed a sucrose-rich diet supplemented with either cystine or cholesterol: relationships with lipoprotein profiles

To study the relationships between lipolytic activities and plasma lipoprotein levels in rats, three diets were given for 8 weeks: a semipurified diet (based on sucrose, casein and lard) and this diet enriched with 5% cystine or with 1% cholesterol. Both supplemented diets induced hypercholesterolemia. Lipoprotein analysis by density gradient ultracentrifugation of plasma indicated that hypercholesterolemia of cystine-fed rats (+52%) was characterized by an increased cholesterol level in high-density lipoprotein (HDL; +131%) and low-density lipoprotein 2 (LDL2; +147%), the lipoprotein fraction containing essentially apolipoprotein-E-rich high-density lipoproteins (HDL1), and was associated with a decreased cholesterol level in triglyceride-rich lipoproteins (TRL: -69%). That obtained by cholesterol feeding (+28%) was due to a large increase in the TRL cholesterol level (+315%) whereas cholesterol was reduced in HDL (-40%) and in LDL2 (-60%). Under these dietary conditions, the activity of hepatic lipase (HL) was measured in liver homogenates and those of both HL and lipoprotein lipase were measured in plasma after heparin injection. The activity of HL (1,783 +/- 132 mU/g liver in control rats) was increased by 48% in cystine-fed rats and decreased by 40% in cholesterol-fed rats. Similar changes were observed in the activity of both lipases measured in postheparin plasma. Highly significant positive correlations linked each lipolytic activity with the level of cholesterol, phospholipids and proteins in LDL2 (HDL1-rich fraction) and in HDL. In contrast, significant negative correlations were found between all of the TRL components and the activity of the lipases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aging accelerates dietary lard-induced increase in blood pressure in rats

We investigated whether the dietary lard-induced increase in blood pressure (BP) is accelerated in aged rats compared to young ones. Three-month-old (young group), 10-month-old (middle-age group), and 18-month-old (older group) F344/N male rats were used. The rats were fed either chow alone or chow in which 50% of the energy content was from substituted lard. Systolic BP (SBP) and body weights (BW) were determined weekly during each 7-week feeding period. A Steady-state plasma glucose (SSPG) method was used to determine the insulin sensitivity. Bilateral testicular fat mass (epididymal fat; Epi-F) was removed in order to evaluate weight (Epi-FW). SBP began to increase at 2 weeks in the older lard-fed group, at 4 weeks in the middle-age lard-fed group, and at 5 weeks in the young lard-fed group after feeding was begun. There was no significant difference in the basal values of SBP among any ages-groups of the rats. After 4 weeks of lard feeding, increases in SBP, plasma insulin, leptin level, SSPG and Epi-FW/BW were observed in the older lard-fed group. In the younger rats, however, only hyperinsulinemia developed. At 7 weeks, increased BP in the younger rats was accompanied by increased plasma leptin level, SSPG and Epi-FW/BW. In summary, aging accelerates development of a dietary lard-induced increase in BP, which may be caused by the hyperleptinemia that may be the result of increased susceptibility to insulin resistance and/or visceral adiposity in older rats.     

Development of dietary obesity in rats: influence of amount and composition of dietary fat.

This study was conducted to examine long-term effects of amount and type of dietary fat on body weight and body composition. Adult male Wistar rats were fed high fat (HF; 60% of calories) or low fat (LF; 20% of calories) diets for 28 weeks. Half of the rats in each condition received diets with saturated fat (lard) (S) and the remainder received diets with polyunsaturated fat (corn oil) (U). From 28-39 weeks, HF rats were switched to LF diets (fat type remained constant). From 40-50 weeks, previously HF fed rats were weight-matched to rats in the LF fed groups. HF rats became fatter than LF rats during weeks 1-28 and remained heavier and fatter from weeks 28-39. During weeks 1-28, type of dietary fat had no effect on total body fat in either HF or LF rats, but during period 2 (weeks 28-39), U rats were heavier and fatter than S rats. There was some indication that U diets were associated with greater accumulation of fat in subcutaneous adipose tissue depots than S diets. From 40-50 weeks, rats previously fed the HF diet required less food to maintain their body weight than did LF diet rats. In summary, these results suggest that although both amount and type of dietary fat can affect body weight and body composition, the effects of the type of fat are less than those of amount of dietary fat.     

Adaptive response of rats with diet-induced adiposity to energy restriction

Groups of 4-week old, male Osborne-Mendel rats were given high fat diet (HFD) for 12 weeks; one group was fed control diet (CON) for 28 weeks. HFD rats were transferred to control diet (HFDCON) and diets restricted to 80% (HFDR80) or 60% (HFDR60) of HFDCON intake for another 16 weeks, while one group continued on HFD. Body, liver and epididymal adipose tissue (EPI) weight, and the EPI/body weight ratio of HFDR60 group decreased significantly. EPI lipid content and total lipoprotein lipase activity also declined in response to 40% restriction. Overall, the data indicate that 40% energy restriction can stabilize body weight at a reduced level, and mobilize adipose lipid to meet the energy needs of HFD rats.     

Characterization of high-density lipoprotein binding to guinea pig hepatic membranes: effects of dietary fat quality and cholesterol feeding

The effects of dietary fat quality and cholesterol intake on expression of guinea pig hepatic membrane high-density lipoprotein (HDL) binding sites were studied. Animals were fed semisynthetic diets containing 7.5% (wt/wt) of either corn oil (CO), olive oil (OL), or lard. The cholesterol diet was prepared by incorporating 0.25% recrystallized cholesterol into standard guinea pig chow. Plasma cholesterol levels of guinea pigs on the CO diet were significantly lower (P less than .02) than animals on the OL or lard diets. HDL cholesterol levels did not differ between the polyunsaturated, monounsaturated, and saturated dietary fat groups. Guinea pigs on the high cholesterol diet had increased total and HDL cholesterol levels compared with animals on the chow diet (P less than .01). Initial studies demonstrated that HDL binding to hepatic membranes was temperature-dependent. A threefold increase in binding was observed when assays were performed at 37 degrees C, as compared with 4 degrees C, for all membrane preparations. Dietary fat quality and dietary cholesterol intake significantly altered HDL binding to hepatic membranes with increased HDL binding to membranes of animals fed polyunsaturated fat and the high cholesterol diet. At 37 degrees C, HDL binding to hepatic membranes of CO-fed animals was 26% and 46% higher than for membranes of OL- and lard-fed guinea pigs, respectively. A high cholesterol intake increased HDL binding by 24% at both 4 degrees C and 37 degrees C. Scatchard analysis demonstrated that while membrane affinity for HDL (Kd) was not affected by diet, changes did occur in the total number of HDL binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired thermoregulation in cold-exposed rats with hypothalamic obesity

Rats with obesity-producing, hypothalamic knife cuts were fed a high fat diet and placed in the cold (2 degrees C) for six days starting 3, 11, or 24 days after surgery. Between surgery and cold exposure, knife-cut rats consumed 90% to 122% more energy and gained more weight (32 +/- 4, 112 +/- 5, and 241 +/- 9 g) than sham-operated rats (15 +/- 2, 34 +/- 2, and 58 +/- 3 g). When exposed to cold, sham-operated rats increased (22% to 30%) energy intake whereas knife-cut rats decreased (5% to 51%) intake. After 24 hours at 2 degrees C body temperatures of knife-cut rats were 1.2, 0.7, and 0.7 degrees less than those of control rats; body temperatures continued to decrease to 2.9, 3.0 and 2.5 degrees less than control rats after six days at 2 degrees C. Fasting for 12 hours at 2 degrees C caused a further reduction in body temperature to 4.9, 4.8, and 5.9 degrees less than in control rats. Cold exposure increased urinary excretion of norepinephrine and epinephrine (indicators of sympathoadrenal activity) in all rats. Guanosine diphosphate (GDP) binding to brown adipose tissue (BAT) mitochondria (an indicator of the thermogenic capacity of the tissue) was similar in cold-exposed, knife-cut, and sham-operated rats. Cold acclimation before hypothalamic knife-cut surgery prevented the cold-induced decrease in body temperatures of knife-cut rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary fat-induced increase in blood pressure and insulin resistance in rats

OBJECTIVES: To determine whether the dietary-fat-induced increase in blood pressure is caused by excess energy intake or the fat composition of the diet, what type of fat increases the blood pressure, and whether insulin resistance is involved in the dietary-fat-induced increase in blood pressure. METHODS: In a series of experiments, rats received: chow alone or chow supplemented with lard or sucrose to provide 33% of a total energy content increased by 50%; chow alone or chow in which 50% of the energy content was from substituted lard, safflower oil or medium-chain triglyceride oil; or chow alone or chow in which 50% of the energy content was from substituted lard, with or without troglitazone. Systolic blood pressure (SBP) was measured every week during each 8-week feeding period. A steady-state serum glucose method was used to determine the insulin sensitivity after the lard substitution with or without troglitazone. RESULTS: Both the lard and sucrose enrichment increased SBP and body weight compared with controls. Lard substitution significantly increased SBP and immunoreactive insulin, although body weight did not differ from control. Neither a diet substituted with safflower oil nor one substituted with medium-chain triglyceride oil influenced SBP. Troglitazone completely inhibited the increase in SBP and immunoreactive insulin induced by the lard. The steady-state serum glucose concentration was significantly greater after the lard substitution than after isoenergetic chow; this effect also was reversed by troglitazone. CONCLUSION: Chronic feeding with lard increased SBP in rats, independently of excess energy intake. Of the fats tested, lard exerted an intrinsic pressor effect. Troglitazone reversed the lard-induced increase in SBP.     

Acute effects of fat and carbohydrate on metabolic rate in normal, cold-acclimated and lean and obese (fa/fa) Zucker rats

The rise in metabolic rate after intragastric feeding with fat and carbohydrate was enhanced in cold-acclimated (5 degrees C) rats and diminished in warm-acclimated (30 degrees C) rats compared to controls (24 degrees C), but the response was largest in cold-acclimated animals intubated with fat. These acute effects of nutrients were almost completely abolished by beta-adrenergic blockade with propranolol in all groups, while the parasympathetic antagonist atropine sulphate enhanced the responses in control rats, but had little effect in cold-acclimated animals. Feeding carbohydrate produced similar increases in interscapular brown adipose tissue (BAT) temperature in control and cold-acclimated rats, but fat caused a much greater rise in the latter group. The thermic effects of both nutrients were lower in genetically obese Zucker rats than in their lean littermates. Atropine slightly increased the thermic responses to fat and carbohydrate in the lean Zucker rats and caused marked potentiation in obese rats intubated with fat, but did not alter the effect of carbohydrate in the obese animals These data suggest that the size of the acute rise in metabolic rate after fat and carbohydrate is dependent on the thermogenic capacity of the animal. The response to fat was particularly large in cold-acclimated rats, where BAT activity is high, possibly due to a direct action of fat on the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

A reciprocal interaction between food-motivated behavior and diet-induced obesity

OBJECTIVES: One of the main causes of obesity is overconsumption of diets high in fat and sugar. We studied the metabolic changes and food-motivated behavior when rats were subjected to a choice diet with chow, lard and a 30% sucrose solution (high fat high sugar (HFHS)-choice diet). Because rats showed considerable variations in the feeding response to HFHS-choice diet and in food-motivated behavior, we investigated whether the motivation to obtain a sucrose reward correlated with the development of obesity when rats were subsequently subjected to HFHS-choice diet. METHOD: We first studied feeding, locomotor activity and body temperature, fat weights and hormonal concentrations when male Wistar rats were subjected to HFHS-choice diet for 1 week. Second, we studied sucrose-motivated behavior, using a progressive ratio (PR) schedule of reinforcement in rats that were subjected to the HFHS-choice diet for at least 2 weeks, compared to control rats on a chow diet. Third, we measured motivation for sucrose under a PR schedule of reinforcement in rats that were subsequently subjected to HFHS-choice diet or a chow diet for 4 weeks. Fat weights were measured and correlated with the motivation to obtain sucrose pellets. RESULTS: One week on the HFHS-choice diet increased plasma concentrations of glucose and leptin, increased fat stores, but did not alter body temperature or locomotor activity. Moreover, consuming the HFHS-choice diet for several weeks increased the motivation to work for sucrose pellets. Furthermore, the motivation to obtain sucrose pellets correlated positively with abdominal fat stores in rats subsequently subjected to the HFHS-choice diet, whereas this correlation was not found in rats fed on a chow diet. CONCLUSION: Our data suggest that the motivation to respond for palatable food correlates with obesity due to an obesogenic environment. Conversely, the HFHS-choice diet, which results in obesity, also increased the motivation to work for sucrose. Thus, being motivated to work for sucrose results in obesity, which, in turn, increases food-motivated behavior, resulting in a vicious circle of food motivation and obesity.     

Brain uptake of ketones in rats with differing susceptibility to dietary obesity

The effect of a low- and high-fat diet on the transport of 3-hydroxybutyrate and glucose across the blood brain barrier has been measured in two strains of animals that have a marked difference in the degree of obesity that develops when they eat a high fat diet. The S 5B/Pl rats are resistant to dietary obesity whereas the Osborne-Mendel rats readily develop obesity when eating a high-fat diet. The transport of 3-hydroxybutyrate and glucose across the blood-brain barrier was measured as the ratio of radioactive compound (3-hydroxybutyrate or glucose) to radioactively labeled water by the technique of Oldendorf. The uptake of 3-hydroxybutyrate was significantly higher in the S 5B/Pl rats than in the Osborne-Mendel rats when they were eating either the low-fat diet or the high-fat diet. In addition, there was a significant increase in the transport of 3-hydroxybutyrate in the animals of both strains when eating the high-fat diet as compared to the low-fat diet. However, there was no difference in the transport of glucose between the two strains of rats whether they ate a low-fat or high-fat diet. These data are consistent with the hypothesis that resistance to dietary obesity is associated with increased transport of 3-hydroxybutyrate across the blood-brain barrier.     

Effects of diet and exercise on the in vivo rates of the triglyceride-fatty acid cycle in adipose tissue and muscle of the rat

The effects of feeding a low-protein diet (5 percent w/w) and daily exercise on the rates of substrate (futile) cycling between triglyceride and fatty acids (TG-FA cycle) were studied in rats in vivo using a radiochemical assay that involves following the incorporation of tritium from 3H-H2O into the fatty acid and glycerol moieties of triglyceride. Sixty-four rats were fed either a purified control diet (COND) consisting of 70 percent carbohydrate, 20 percent protein, 5 percent fat or an experimental low protein (LPD) diet consisting of 80 percent carbohydrate, 5 percent protein and 10 percent fat (w/w) and were either exercised six days weekly or remained sedentary for six weeks. Both LPD and exercise training (EXT) were found to increase significantly the rate of TG-FA substrate cycling above the rates observed in dietary and sedentary control groups. The LPD increased significantly the rate of cycling in interscapular brown adipose (IBAT), while adipose (WAT) and diaphragm muscle. EXT increased the rates of substrate cycling in soleus, heart, and diaphragm muscle and WAT. Rate of cycling in cardiac or skeletal muscle was one-twentieth that found in adipose tissue. There were also sex differences in the rate of substrate cycling. Substrate cycling in soleus and heart muscle of male animals were consistently higher than respective female treatment groups. Sedentary and EXT LPD animals weighed significantly less than but consumed a similar amount of food to the respective COND animals. These data provide the first in vivo evidence that the rate of substrate cycling can be increased by diet or by exercise training. The possible importance of TG-FA and other substrate cycles on efficiency of energy metabolism and etiology of obesity are discussed.     

Modulation of fatty acid synthesis in vivo in brown adipose tissue, liver and white adipose tissue of cold-acclimated rats

The present experiment was an appraisal of the relative importance of fatty acid synthesis in brown adipose tissue (BAT) in young 28 or 5 degrees C adapted rats (9 weeks old). With a low-fat diet in vivo incorporation of 3H2O into BAT fatty acids was 8 times lower during the day than during the night and was not modified by a 6-hour fast during the day (28 degrees C). Cold acclimation doubled (night) or increased 8 times (day) BAT lipogenesis. Fasting led to a halving of the diurnal rate. A high-fat diet led to large decrease in synthesis rate during the night but had a weak effect on diurnal synthesis. The specific activity of fatty acids was 3 times lower in phospholipids than in neutral lipids. A comparison between 9- and 15-week-old rats indicated that in older warm-adapted rats BAT lipogenesis decreased by half but that cold stimulation was unaltered. These results were compared with hepatic and epididymal white adipose tissue lipogenesis. In conclusion, we showed that BAT of 5 degrees C rats is an important but not the major site for the conversion of carbohydrate to fat and that the proportional involvement of each tissue is age-dependent.