Effect of exercise and tepary bean type diet on body composition and fat accretion in obese Zucker rats

OBJECTIVE: The effectiveness of a tepary bean high fat type diet, compared to a purified type high fat diet and exercise, on body composition in fatty Zucker rats was determined. SUBJECTS AND DESIGN: Approximately 6-week-old female fa/fa Zucker rats were divided into four groups of 10 rats each: TE, fed the tepary bean type diet and exercised; TN, fed the tepary bean type diet and not exercised; CE, fed the purified type control diet and exercised; CN, fed the purified type control diet and not exercised. The exercise modality was treadmill running and the experiment lasted 13 weeks. MEASUREMENTS: Body weight, cumulative food intake, body composition, weights of adipose tissues and liver, heart and gastrocnemius muscle. RESULTS: At the end of the 13 week experiment, TE rats weighed 511 +/- 22 g and were significantly lighter than TN, 588 +/- 15 g; CE, 606 +/- 22 g; and CN, 660 +/- 27 g. All are means +/- s.e.m. The carcass of CN rats had 58, 20 and 13% more fat than TE, TN and CE rats, respectively; P < 0.01. Lean body mass was the same for all the groups of rats and ranged from means of 216-228 g. However, TE rats had significantly more fat free dry mass (FFDM) than CN rats; 68 +/- 4 vs 58 +/- 2 (means +/- s.e.m.) and tended to have more FFDM than TN and CE rats. Inguinal fat depots weighed 20-30% less in T than in C rats (diet comparisons) and also 20-30% less in E than in N rats (exercise comparisons). Perirenal/retroperitoneal fat depots weighed 25% less in TN than in CN rats and 38% less in TE than in CE rats. Exercise did not reduce perirenal/retroperitoneal fat depot weights. Parametrial fat depot weights were not influenced by diet or exercise. CONCLUSIONS: In diets which provided 37% of the energy from fat, the incorporation of tepary beans attenuated weight gain, and subcutaneous and visceral fat gain compared to a purified type diet. Exercised rats gained less weight and subcutaneous, but not visceral fat, than non-exercised rats.     

Growth and development of the kidneys, heart and liver in S 5B/P1 and Osborne-Mendel rats fed high or low-fat diets

Male Osborne-Mendel (OM) and S 5B/P1 rats were overfed from birth to 24 or 105 days. The effects of feeding a diet with 44 per cent or 3 per cent (w/w) fat, supplementary feeding during the suckling period, and reduced litter size, on body weight and on the weight and cellularity of the heart, liver and kidneys were evaluated. Three overfeeding techniques were used: (1) feeding a high fat diet, (2) reducing litter size, (3) force-feeding from 1-24 days. The overfeeding technique which exerted the greatest effect on growth was feeding a high-fat diet. In comparison to OM rats that suckled dams fed the low-fat diet, body weight as well as organ weight, DNA, protein and lipid were significantly elevated in 24-day-old OM rats that suckled dams fed the high-fat diet. In comparison to OM rats not overfed, the organs of the rats fed the high-fat diet contained significantly more cells at both 24 and 105 days, except for the heart which by 105 days contained more protein, but not DNA. Liver weight and growth in S 5B/P1 rats was similar, regardless of dietary manipulation. Compared to S 5B/P1 rats that suckled dams fed the low-fat-diet, kidneys were 12 per cent larger at 24 days and 19 per cent larger at 105 days in rats that suckled dams fed the high-fat diet and were thereafter fed a high-fat diet. Hearts of the latter rats were larger than the former rats at 24 days, but not at 105 days.     

Energy restriction with high-fat diet enriched with coconut oil gives higher UCP1 and lower white fat in rats

OBJECTIVE: To investigate the effects of overfeeding on a high fat diet, enriched in coconut oil, and the influence of food restriction on the uncoupling protein (UCP1) expression and on body fat content. DESIGN AND SUBJECTS: In experiment I, female Wistar rats were fed ad libitum either a normal-fat diet (control group, C) or a high-fat diet (HF), enriched in coconut oil, for 7 weeks. In experiment II, HF rats after finishing experiment I were fed (for 3 weeks) either the normal-fat diet (group CAHF, Control After High Fat) or food restricted diets which provided 60% of the energy intake of group CAHF: a group fed a low-energy, normal-fat diet (LENF) and another fed a low-energy, high-fat diet (LEHF). MEASUREMENTS: Body and fatty depot weights. Food intake. Protein and UCP1 levels of interscapular brown adipose tissue. RESULTS: High-fat diet feeding promoted an increase in body fat content, body weight and UCP1 levels. Energy restriction induced similar body weight reduction in groups LENF and LEHF. However, some adipose depots were more strongly reduced in the rats fed the high-fat diet enriched in coconut oil (group LEHF) than in the rats fed the normal-fat diet (Group LENF). Specific UCP1 was 2.0 (group LENF) and 3.4 (group LEHF) times higher than in controls (group CAHF). CONCLUSION: The coconut-oil enriched diet is effective in stimulating UCP1 expression during ad libitum feeding and in preventing its down regulation during food restriction, and this goes hand in hand with a decrease of the white fat stores.     

The effects of a high fat diet on leptin mRNA, serum leptin and the response to leptin are not altered in a rat strain susceptible to high fat diet-induced obesity

Osborne-Mendel (OM) and S5B/Pl rats differ in their sensitivity to develop obesity when fed a high fat (HF) diet; OM rats become obese, whereas S5B/Pl rats remain thin. We have investigated the possibilities that either an impaired leptin response or resistance to leptin action underlies the sensitivity to this form of obesity in OM rats. In Experiment 1, OM and S5B/Pl rats fed a nonpurified diet were killed at d 0 or were fed either a HF (56% fat energy) or a low fat (LF, 10% fat energy) diet for 2 or 7 d. The HF diet increased serum leptin significantly by d 2 to levels that were similar in both rat strains. At 7 d, leptin levels were lower than at d 2 but remained higher than levels in the d 0 control groups. The leptin mRNA:18S RNA ratio in epididymal adipose tissue increased to higher levels in HF-fed OM rats than in S5B/Pl rats fed that diet. However, although the LF diet had no effect in S5B/Pl rats, it increased leptin mRNA levels in epididymal adipose tissue of OM rats compared with the controls fed the nonpurified diet. In Experiment 2, OM and S5B/Pl rats were fed HF or LF diets for 5 wk. At that time, their feeding response to a range of leptin doses (0, 1, 5 or 10 microgram) given intracerebroventricularly was tested after overnight food deprivation. There was a similar dose-dependent reduction in energy intake in response to leptin in both OM and S5B/Pl rats. These responses were independent of the diet. The data suggest that the susceptibility of OM rats to HF diet-induced obesity is not related to either a loss of central sensitivity to leptin or a failure to enhance leptin production acutely, although the failure to maintain chronically increased levels of serum leptin could contribute to the obesity.     

Glucose contribution to in vivo synthesis of glyceride-glycerol and fatty acids in rats adapted to a high-protein, carbohydrate-free diet

Triacylglycerol (TAG) synthesis from all carbon sources and from glucose carbon was evaluated in rats fed a high-protein, carbohydrate-free (HP) diet or control diet by determining simultaneously in the same animal the rate of incorporation of 3H2O and of 14C-glucose into the two TAG moieties in the carcass, liver, and retroperitoneal and epididymal adipose tissue. Incorporation rates of 3H2O into TAG-fatty acids (FAs) in the two adipose tissues and in liver were reduced in HP rats to about 20% and 50%, respectively, of the rates in control rats. In the two experimental groups, glucose was a poor precursor for FA synthesis, contributing only 22.8% of whole-body (carcass plus liver) total FA synthesis in control rats and even less (14%) in HP rats. In contrast to the reduction in FA synthesis, incorporation of 3H2O into TAG-glycerol in HP rats did not differ significantly or was even higher (in epididymal tissue) versus the control level. In all tissues of both HP and control rats, the rate of 14C-glucose incorporation into TAG-glycerol was much higher than the rate of incorporation into FA. Glyceroneogenesis, estimated by subtracting TAG-glycerol synthesis from glucose from the rate obtained with 3H2O, was significantly increased in adipose tissue from HP rats, with almost all of the glycerol formed by this route being used to esterify preformed FAs. It is suggested that the increased adipose tissue glyceroneogenesis is important for esterification of diet-derived FA and preservation of body fat stores in rats adapted to the HP diet.     

Positive association between dietary fat intake and risk of gastric stump carcinoma in rats

Effect of high- and low-fat diets on gastric stump carcinogenesis was experimentally investigated. A total of 130 Wistar male rats weighing 250-300 g received either sham operation or Billroth II partial gastrectomy, the resection of the distal two-thirds glandular stomach and reconstruction of gastro-jejunostomy. After surgery, each group of rats was switched from a standard diet (CRF-1) to a special diet containing either 15% soybean oil (high-fat) or 0.5% soybean (low-fat), fed ad libitum and tap water, and were killed 50 weeks after surgery. Gastric tumours were observed only in the animals that underwent gastrectomy while no tumours were detected in the animals following the sham operation. Tumours located invariably at the gastrojejunostoma, were carcinomas or adenomas in histology. Carcinomas developed in 12 of 29 gastrectomy animals (41%) fed the high-fat diet and 4 of 27 gastrectomy animals (15%) fed the low-fat diet. The difference was significant (P < 0.05). The incidence of adenoma was also significantly higher in the gastrectomy animals fed the high-fat diet (38%) than that in those fed the low-fat diet (15%) (P < 0.05). A daily faecal output of bile acids was significantly greater in the gastrectomy animals fed the high-fat diet (19.0 +/- 16.4 micromol/day) than that in those fed the low-fat diet (11.2 +/- 6.2 [micromol/day; P < 0.05). This study suggests that increased fat intake is associated with a high risk of gastric stump carcinoma.     

Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study

We conducted a controlled feeding study to evaluate the effects of fat and fiber consumption on plasma and urine sex hormones in men. The study had a crossover design and included 43 healthy men aged 19-56 y. Men were initially randomly assigned to either a low-fat, high-fiber or high-fat, low-fiber diet for 10 wk and after a 2-wk washout period crossed over to the other diet. The energy content of diets was varied to maintain constant body weight but averaged approximately 13.3 MJ (3170 kcal)/d on both diets. The low-fat diet provided 18.8% of energy from fat with a ratio of polyunsaturated to saturated fat (P:S) of 1.3, whereas the high-fat diet provided 41.0% of energy from fat with a P:S of 0.6. Total dietary fiber consumption from the low- and high-fat diets averaged 4.6 and 2.0 g.MJ-1.d-1, respectively. Mean plasma concentrations of total and sex-hormone-binding-globulin (SHBG)-bound testosterone were 13% and 15% higher, respectively, on the high-fat, low-fiber diet and the difference from the low-fat, high-fiber diet was significant for the SHBG-bound fraction (P = 0.04). Men's daily urinary excretion of testosterone also was 13% higher with the high-fat, low-fiber diet than with the low-fat, high-fiber diet (P = 0.01). Conversely, their urinary excretion of estradiol and estrone and their 2-hydroxy metabolites were 12-28% lower with the high-fat, low-fiber diet (P < or = 0.01). Results of this study suggest that diet may alter endogenous sex hormone metabolism in men.     

A high glycemic index starch diet affects lipid storage-related enzymes in normal and to a lesser extent in diabetic rats

The of this study was to evaluate the chronic effects of a high (waxy corn) vs. a low (mung beans) glycemic index starch diet on the lipogenic enzymes, fatty acid synthase (FAS) and lipoprotein lipase (LPL). Normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats consumed a diet containing 575 g/kg carbohydrates either as waxy cornstarch (WCS) or as mung bean starch (MBS). After 3 wk, neither body weights nor relative epididymal fat pad weights differed. In diabetic rats, the WCS diet induced high basal plasma insulin levels. Plasma triglycerides were not significantly affected by diet in either normal or diabetic rats. Adipose tissue and liver LPL activities were not modified by the type of starch in the diet. In normal rats, FAS activity and gene expression in epididymal adipose tissue but not in liver were greater in rats consuming the WCS diet than in those consuming MBS. To evaluate the implication of insulin in this regulation, two genes regulated by insulin [GLUT4 and phosphoenolpyruvate carboxykinase (PEPCK)] were also studied. The high glycemic index WCS diet compared with the low glycemic index MBS diet resulted in lower hepatic PEPCK mRNA in both normal and diabetic rats. Normal, but not diabetic rats fed WCS had greater GLUT4 gene expression in adipocytes than did those fed MBS. We conclude that the total replacement of 575 g/kg low glycemic index starch by a high glycemic index starch for 3 wk caused the following in normal rats: 1) high FAS activity and mRNA in adipose tissue but not in liver and 2) high GLUT4 gene expression in adipose tissue. In both normal and diabetic rats this same diet resulted in lower hepatic PEPCK mRNA. Therefore, high glycemic index starch diet is implicated in stimulating FAS activity and lipogenesis and might have undesirable long-term metabolic effects.     

Noncompensation of adipose mass in partially lipectomized mice and rats

The effects of surgical ablation of adipose tissue were studied in normal mice and rats. It was found that: 1) restortation of adipose tissue does not occur locally in epididymal fat pads of young rats. 2) Bilateral epididymal fat pad removal in mice disrupts the testes and causes the other fat depots to accumulate excess lipid, but these effects are not sustained; After a sufficient recovery period, testes appear normal and no excess lipid is found in the remaining depots; 3) Temporary enlargement of remaining depots is probably due specifically to epididymal pad removal. It does not occur in response to inguinal depot removal, nor in response to disruption of the testes alone; 4)The quantity of lipid stored by a rapidly growing mouse depends on the number of intact depots in the mouse. These results suggest that surgical removal of fat does not lead to compensatory growth of fat. Autoregulation of adipose tissue mass, if it occurs, most likely operates through detection of adipocyte size rather than adipocyte number or total fat mass.     

Chemoprevention of colon cancer by organoselenium compounds and impact of high- or low-fat diets

BACKGROUND: Observational and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of colon cancer. However, many forms of selenium are toxic. Consequently, the development of efficacious compounds with low toxicity has been pursued. PURPOSE: Two synthetic organoselenium compounds, p-methoxy-benzyl selenocyanate (p-methoxy-BSC) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC), were tested for their ability to inhibit colon carcinogenesis in rats that were treated with the carcinogen azoxymethane and fed low- or high-fat diets. METHODS: Groups of 5-week-old male F344 rats (42 animals/ group) were fed either a high-fat diet or a low-fat diet with or without added p-methoxy-BSC (10 or 20 parts per million [ppm]) or p-XSC (20 ppm). Two weeks later, 30 animals in each group received a subcutaneous injection of azoxymethane (15 mg/kg body weight); 1 week later, they received a second injection. The remaining 12 rats in each group received two injections of saline. Three days after the second injection of carcinogen or saline, animals being fed diets with p-methoxy-BSC or p-XSC were switched to corresponding organoselenium-free low- or high-fat diets for the remainder of the study to determine the effects of the selenium compounds on the initiation phase of colon carcinogenesis. At that time, groups of animals that had been maintained on organoselenium-free low- or high-fat diets were switched to diets containing p-methoxy-BSC or p-XSC until the end of the study to determine the effects of these compounds on the postinitiation phase of colon carcinogenesis. All animals were killed during the 38th week after azoxymethane or saline treatment, and histopathologic analysis of the colon tumors was performed. Colon tumor incidence and multiplicity were analyzed statistically. RESULTS: No obvious toxic effects were observed following dietary administration of 10 or 20 ppmp-methoxy-BSC or 20 ppm p-XSC. Administration of 20 ppm p-methoxy-BSC in a high-fat diet during the initiation and postinitiation phases of colon carcinogenesis significantly (statistically) reduced colon tumor incidence; 10 ppmp-methoxy-BSC in a high-fat diet significantly reduced colon tumor incidence but only when it was given during the postinitiation phase. Colon tumor incidence was also significantly reduced when 20 ppm p-XSC was given in a high-fat diet during the initiation phase of colon carcinogenesis. When 20 ppm p-XSC was administered in either a high-fat diet or a low-fat diet during the postinitiation phase, both colon tumor incidence and multiplicity were significantly reduced; the greatest reductions were in animals fed a low-fat diet. CONCLUSIONS: In this model system, p-methoxy-BSC and p-XSC are effective agents for the chemoprevention of colon cancer. The effects of p-XSC were enhanced in animals fed a low-fat diet.     

Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice

The C57BL/6 (B6) mouse is more sensitive to the effects of a high-fat diet than the A/J strain. The B6 mouse develops severe obesity, hyperglycemia, and hyperinsulinemia when fed this dietary regimen. This study was conducted to determine the effects of dietary fat and sucrose concentrations on body composition and intestinal sucrase (EC 3.2.1.48) and maltase (EC 3.2.1.20) activity in these two mouse strains. High-fat diets, regardless of sucrose content, resulted in significant weight gain, higher body fat, and lower body protein and water content in both strains of mice. The shift toward higher body fat and lower protein and water content was far greater in the B6 strain. Low-fat, high-sucrose diets resulted in lower body weight in both strains, as well as significantly greater body protein content in B6 mice. Analysis of intestinal sucrase showed that the enzyme was less active in B6 mice when the diet was high in sucrose. Both sucrase and maltase had lower activity in the presence of high dietary fat in both mouse strains. The percent reduction of intestinal enzyme activity due to dietary fat was similar in both strains. The B6 mouse exhibits disproportionate weight gain and altered body composition on a high-fat diet. This coupled with the reduced body weight and increased body protein on a low-fat, high-sucrose diet suggests that factors-relative to fat metabolism rather than sucrose metabolism are responsible for obesity.     

Changes in fatty acid composition in rat adipose tissue induced by dietary obesity

The aim of the study was to evaluate the effects of cafeteria feeding on the composition of fatty acids in retroperitoneal fat pad and also to determine what happens to fatty acids when rats previously fed the cafeteria diet are returned to regular rat chow. The study of the post-cafeteria rats enabled us to determine the effects of dietary induced excess weight in the absence of artefactual interferences from the diet because these rats, unlike the cafeteria obese rats, ate the same diet as controls. In response to cafeteria feeding there were increases in the majority of adipose tissue fatty acids. However, significant decreases were observed in the relative proportions of 18:2n-6 and in two related n-6 polyunsaturated fatty acids (18:3n-6 and 20:3n-6), as well as in 16:1. In the post-cafeteria obesity model the previous dietary influence on fatty acid composition was still evident. The maintenance of both the high levels and proportions of 18:1 and the decrease of 16:1 percentage in the post-cafeteria rats argues in favour of an alteration in the activity of the elongation metabolic pathway. Certain changes affecting polyunsaturated fatty acid adipose depot composition of obese rats, mainly the decreased levels of 18:2n-6, are long lasting and could be related to the maintenance of the obese status. On the whole, although the fatty acid composition of adipose tissue is influenced by the composition of the diet, there are some differences in both the maintenance of the effects and also in the selectivity of adipose tissue for the different fatty acids of obese and lean rats.     

Exercise, dietary obesity, and growth in the rat

Four regimens: high-fat diet, exercised (I); chow, exercised (II); high-fat sedentary (III); and chow, sedentary (IV) were initiated in 35-day-old male rats. Growth was exponential in I and II and exponential progressing to rectilinear in III and IV. The exponential model predicted the decreasing rank order in asymptotic weight to be: III, IV, I, II. Body composition data (9 components) showed rank order in masses of fat and the fat-free body mass compartment (FFBM) to be the same as for asymptotic live weight. The rectilinear growth mode probably reflected fat accretion. High-fat diet increased and treadmill exercise decreased FFBM, the latter being reversible. These effects depended on regimen initiations by the 5-7th wk of age. During growth, masses of H2O, muscle, and skin increased as functions of body size; bone as a function of age; and heart, liver, gut, testevity, and diet. Growth in body size was expressed more precisely with FFBM, instead of live weight, as the index of size.     

Silage or limit-fed grain growing diets for steers: II. Empty body and carcass composition

The influence of energy source (silage- or grain-based) on empty body and carcass composition and adipocyte cellularity independent of rate of gain was tested. Sixty-four Angus steers were allotted to either a forage (ad libitum) or grain (limit-fed) diet for a growing phase (145 d) followed by 45, 75, or 105 d of ad libitum access to a grain-based diet. Eight steers were slaughtered initially and eight from each treatment were slaughtered at the end of the growing phase, and at each of the termination dates. The silage growing diet consisted (DM basis) of 55% sorghum silage (approximately 24% dry matter), 22% alfalfa hay, 11% ground shelled corn, and 11% soybean meal. The grain-based growing diet was composed of 77% ground shelled corn, 5% soybean meal, 14% cottonseed hulls, 3% molasses, and 1% salt and mineral; it was limit-fed to produce the same rate of gain as the silage diet. No implants or ionophores were used. At the end of the growing phase, the steers fed grain were heavier and had a higher percentage of fat in the empty body (24 vs 19% fat) and the carcass (26 vs 21% fat) than did steers fed forage. Rate of gain during the growth phase was related positively to percentage of carcass fat; when corrected for fill, data for both diets fit one regression line for fat vs rate of gain. When adjusted for gain during the growing phase, fat content was not different in empty body or carcass, but internal fat was higher (P < .10) for steers fed grain. After 45 d on the finishing diet, carcass fat remained low (23%), but after 75 and 105 d, fat content reached 27%. Source of energy did not detectably affect carcass composition independent of rate of gain. Cell size of adipocytes from four adipose depots increased with time on feed but were not affected by diet during the growing phase. Lean Choice beef can be produced in only 45 d in the feedlot with medium-framed Angus cattle.     

Determination of total proteinuria: a comparative study of automated trichloracetic acid and pyrogallol red techniques for samples with monoclonal light chains

Chronic feeding of dehydroepiandrosterone (DHEA) and its sulfated metabolite, dehydroepiandrosterone sulfate (DHEAS), has previously been reported to decrease hyperglycemia, obesity, cancer, and autoantibody generation in a number of animal models and to increase muscle mass and physiological and psychological well-being in elderly humans, although these latter studies remain controversial. The present study was carried out to determine whether large amounts of DHEAS given orally would prevent the occurrence of spontaneous and iodine-induced autoimmune lymphocytic thyroiditis (LT) and/or spontaneous insulin-dependent diabetes mellitus (DM) in male and female BB/Wor rats. DHEAS was administered by gavage (44 mg/rat/day) or in the chow (133 mg/rat/day) to LT- and DM-prone rats from 30 to 120 days of life; some of these rats also received iodine in the drinking water to enhance the incidence and intensity of LT. Onset of DM requiring protamine zinc insulin and its maintenance dose were assessed. Rats were killed at 90 or 120 days of age and blood, thyroid, adrenals, pancreases, testes, and ovaries were removed. Serum glucose, DHEA, DHEAS, thyroxine (T4), tri-iodothyronine (T3) and thyrotropin (TSH) concentrations were measured in all rats in both experiments. Serum DHEAS concentrations were 10-fold higher in the rats given the steroid by gavage or in the diet compared with levels in control rats. DHEAS administered over a prolonged period of time had no significant effect on body weight, incidence and severity of DM, incidence and intensity of spontaneous and iodine-induced LT, and thyroid, pancreas and testes weights but did significantly decrease adrenal and ovarian weights. Serum T4, T3, and TSH concentrations were similar in control and DHEAS-treated rats. In conclusion, DHEAS did not prevent the occurrence of iodine-induced or spontaneous autoimmune LT or spontaneous DM in the BB/Wor rat, at variance with its reported immunosuppressive effects in other animal models.     

Missed opportunities for prevention: smoking cessation counseling and the competing demands of practice

Activating mutations in and expression of the Ha-ras gene were examined in benign and malignant female Sprague-Dawley rat mammary gland tumors induced by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by a diet high in polyunsaturated fat. Ha-ras mutations were detected in codons 12 and 13 by selective polymerase chain reaction amplification of mutated sequences and nucleotide sequencing. The percentage of Ha-ras mutations in carcinomas from PhIP-treated rats was significantly higher in rats on a low-fat diet than in rats on a high-fat diet (82% (nine of 11) vs 26% (seven of 27), respectively, P < 0.01). In addition, whereas 56% of the carcinomas with Ha-ras mutations from rats on a low-fat diet carried double Ha-ras mutations, none of the carcinomas from rats on a high-fat diet had double mutations. Ha-ras mutations were also detected in benign tumors (largely adenomas) induced by PhIP in rats on different diets; two of eight and three of four benign tumors examined from rats on low-fat and high-fat diets, respectively, had Ha-ras mutations, suggesting that activating Ha-ras mutations alone are not sufficient for PhIP-induced tumors to become malignant. No differences were observed in the level of Ha-ras mRNA expression in the different groups. In our animal model, a high-fat diet increased the incidence and percentage of malignant PhIP-induced mammary gland tumors yet decreased the percentage of carcinomas showing Ha-ras mutations. Thus, the complement of genetic alterations associated with PhIP-induced mammary gland carcinogenesis is probably altered by the level of dietary fat.     

Long-term effects of feeding high carbohydrate diet in pre-weaning period by gastrostomy: a new rat model for obesity

In the present study, we report the long-term metabolic consequences of feeding a milk substitute formula that is high in carbohydrate-derived calories during the suckling period. Male Sprague-Dawley rat pups were raised by gastrostomy on a high carbohydrate (HC) formula or a high fat (HF) formula (which mimicked rat milk composition in macronutrients) during the pre-weaning period (day 4 to 24). These rats were then weaned to a laboratory stock diet and subsequently challenged with a high sucrose diet to augment the development of obesity. The pups receiving the HC formula developed obesity in later life, even though there was no change in the body weight of this group compared to mother-fed (MF) controls or HF formula fed animals during the pre-weaning period. The HC rats were hyperinsulinemic and their growth rates were greater than MF rats starting at day 55. The lipogenic capacity of liver as well as adipose tissues (epididymal and omental) was higher in HC animals compared to MF control animals, as reflected by increases in two key lipogenic enzymes (fatty acid synthase and glucose-6-phosphate dehydrogenase) and in vitro synthesis of lipids. An analysis of adipose tissue morphology in adult rats showed an increase in cell size in epididymal adipose tissue of HC rats compared to the MF group. However, there was no significant difference in cell size in omental adipose tissue between the MF and HC rats. The HF group behaved similarly to the MF control group in growth pattern and measured metabolic parameters.     

Suppression of fatty acids synthesis in brown adipose tissue of mice fed diets rich in long chain fatty acids

The influence of dietary lipid on fatty acid synthesis in brown adipose tissue has been investigated by feeding different high-fat diets to cold-acclimated mice for a period of 2 weeks. Fatty acid synthesis was measured in vivo with 3H2O, and the fats used in the study were maize oil, beef tallow and medium chain triacylglycerol oil. In the mice fed the maize oil and the beef tallow diets fatty acids synthesis was inhibited in all tissue examined--interscapular brown adipose tissue, epididymal white adipose tissue, the liver and the carcass. Synthesis was more inhibited, however, in brown adipose tissue than in other tissues, and the inhibition was greater on the maize oil diet than on the beef tallow. The medium chain triacylglycerol oil had no inhibitory effect on fatty acid synthesis in any tissue, and hepatic synthesis was even elevated on this diet. It is concluded that fatty acid synthesis in brown adipose tissue, as in other lipogenic tissues, is subject to strong suppression by dietary long chain fatty acids, and particularly by linoleic acid.     

Effect of a stearic acid-rich, structured triacylglycerol on plasma lipid concentrations

BACKGROUND: Structured lipids are being incorporated into foods to reduce their energy value. One such lipid is rich in stearic acid. OBJECTIVE: The objective of this study was to compare the effects on plasma lipids of a stearic acid-rich triacylglycerol and a fat rich in palmitic acid in hypercholesterolemic subjects. DESIGN: Fifteen subjects with an average plasma cholesterol concentration of 6.13 +/- 0.80 mmol/L initially ate a low-fat diet for 2 wk (run-in period), followed in random order and blinded fashion by 2 high-fat diets (for 5 wk each) containing foods derived from margarines rich either in palmitic acid or in the structured, stearic acid-rich triacylglycerol. RESULTS: Plasma cholesterol concentrations with the low-fat, the stearic acid-rich, and the palmitic acid-rich diets were not significantly different (5.35 +/- 0.83, 5.41 +/- 0.78, and 5.52 +/- 0.68 mmol/L, respectively) but were significantly lower (P < 0.001) than those measured during the habitual diet period (ie, 2 wk before the study began). Neither HDL cholesterol nor plasma triacylglycerol differed significantly among the 3 study diets. CONCLUSION: A similar increase in the intake of stearic and palmitic acids (differing by approximately 5% of total energy) to ensure a high fat intake resulted in plasma total and LDL-cholesterol concentrations that did not differ significantly from concentrations measured during a period of low-fat intake.     

Evaluation of single cell sources of docosahexaenoic acid and arachidonic acid: a 4-week oral safety study in rats

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are secreted in human milk and consumed by the nursing neonate but are not present in infant formulas currently available in the US. Supplementation of formulas with DHA and ARA may be particularly important for premature infants, who have less accretion of these fatty acids in utero than term infants. Some experts suggest that DHA and ARA should be added to infant formulas. Common sources of these fatty acids (e.g. fish oils, egg yolk lipids) are not optimal for infants in that they contain disproportionate amounts of other fatty acids. This 4-wk study examined the safety of a high-DHA algal oil and a high-ARA fungal oil, blended so that the DHA:ARA ratio approximates that in human milk. Rats were fed the blend at levels representing three, 11 and 22 times the anticipated infant exposure. Control animals were fed either a high-fat diet (13.1%, w/w; equivalent to the fat content of the treated groups) or a low-fat diet (5%, w/w). There were no treatment-related differences in body weight, food intake, organ weights, haematology or clinical chemistry. Thus, this study indicates that a blend of algal and fungal oils is a safe source of DHA and ARA as it produced no adverse effects in rats when administered for 4 wk at levels up to 22 times the expected infant exposure.