High Levels Of Dietary Fat Research Articles

Dietary fat and high energy density diet: Influence on intestinal health, oxidative stressand performance of weaned piglets.

The utilization of dietary components to support gut function and the health of young animals is an important factor for improved performance. The influence of high dietary fat levels in a lowor high energy density diet on the performance of weaned piglets in relation to intestinal absorptive function, amino acid utilization, oxidative stress, and microbial metabolites was assessed in this study. The study examined the effect of two different diets containing either a low energy density/high-fat level or a high energy density/high-fat level. A total of 16 healthy weaners (9.60 ± 0.13 kg) were allocated to one of the two dietary treatments. There were eight weaners per treatment. Results showed that feed intake and body weight gain of weaners were increased by the diet of high energy density/high-fat level (p < 0.05), but the feed efficiency showed an increased tendency of significance (p = 0.05). In the duodenum, the villus height(VH) and VH/crypt depth (CD) ratio (VH:CD) were increased by dietary high energy density/high fat. In the jejunum and ileum, the CD was increased by low energy density/high-fat diet, while the goblet cell count and VH:CD were increased by dietary high energy density/high-fat level. Methionine, lysineand phenylalanine concentrations were increased by high energy density/high-fat diet while low energy density/high-fat diet showed an increased tendency to increase citrulline and ornithine concentrations in the piglet. Oxidative stress marker, lactase enzyme activity and serum calcium concentration were increased by a high energy density/high-fat diet. Increased dietary fat in all diets induced diarrhoea in the weaners (p < 0.01). It was concluded that a dietary high energy density/high-fat diet seems to positively modulate gut absorptive function, serum amino acid (methionine and lysine), calcium levels and increased oxidative stress markers in the weaned piglets.

Lentils counteract the ability of dietary fat to increase adiposity in growing C57BL/6J female mice (1031.4)

Pulse consumption can prevent obesity in rodents challenged with high levels of dietary fat. In the C57BL/6J mouse, high fat diets also have been shown to reduce mammary ductal development. In this study, we hypothesized that dietary lentils would prevent the increased adiposity and diminished mammary ductal development that occurs in high fat‐fed C57BL/6J mice. Female mice (5/treatment) were fed either Harlan‐Teklad 2020x (2020x, 6.5% fat), Harlan TD.88137 (HF, 21% fat, 34% sucrose), or Harlan TD.88137 with cooked, freeze‐dried lentils added at 15% (HFL). After 4 weeks on the diets, females fed HFL had higher (P&lt;0.05) weight gain than both 2020x and HF. However, body fat mass and percent fat were similar among 2020x and HFL, and both lower (P&lt;0.05) than that of HF females. In addition, wet weight of both the parametrial and mammary fat pads were similar among 2020x and HFL, and lower in weight (P&lt;0.05) than HF females. Comparison of mammary ductal morphometry measurements revealed only modest dietary effects. These data demonstrate that dietary lentils can counteract the increased body fatness effect of a high fat diet in growing female mice.Grant Funding Source: Supported by The American Pulse Association

Evaluation of the Contribution of the ATP Binding Cassette Transporter, P-glycoprotein, to in Vivo Cholesterol Homeostasis

P-glycoprotein (Pgp, encoded by ABCB1, commonly known as MDR1), an ATP-dependent transporter with a broad range of hydrophobic drug substrates, has been associated with the in vitro intracellular transport of cholesterol; however, these findings have not been confirmed in vivo. In this manuscript we tested the contributions of Pgp to in vivo cholesterol homeostasis by comparing the cholesterol phenotype of wild type mice with mice lacking both murine isoforms of Pgp (Abcb1a(-/-)/1b(-/-)) by measuring cholesterol absorption, circulating cholesterol, and lipoprotein cholesterol profiles. The mice were fed diets containing normal or high levels of dietary fat (25% vs 45% kcal from fat) and cholesterol (0.02% vs 0.20% w/w) for 8 weeks to challenge their capacity to maintain homeostasis. There were no significant differences in cholesterol absorption, circulating cholesterol levels, and lipoprotein profiles between Pgp knockout and wild type mice fed matching diets. Compensatory shifts were observed in the activation of two key transcription factors involved in maintaining cholesterol balance, the Liver X Receptor and SREBP-2, which may have maintained the wild type phenotype in the knockout mice. Deletion of Pgp affected the molar composition of gallbladder bile, when the mice were fed diets containing high levels of dietary fat, cholesterol, or both. The mole fraction of bile salts was reduced in the gallbladder bile of Pgp knockout mice, while the mole fraction of cholesterol was increased. In this paper, we provide evidence that Pgp knockout mice maintain cholesterol homeostasis, even when challenged with high cholesterol diets. We suggest that the specific shifts in cholesterol regulatory networks identified in the jejunum and liver of the knockout mice may have compensated for the lack of Pgp. Our finding that Pgp knockout mice were unable to maintain gallbladder bile composition when challenged with high dietary fat and/or cholesterol compliments recent reports that Pgp may be a secondary bile salt export pump.

Effects of Fat and Cinnamon Feeding on Adiponectin after Rat Injection with Dexamethasone

Chronically excessive numbers of glucocorticoids are known to induce insulin resistance, which is possibly involved in impairing the insulin signaling in liver, muscle, and adipose tissues. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia ,all of these features are shared by the condition of insulin resistance .Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance [7]. Fatty acid composition in the diet is another mechanism implicated in the development of insulin resistance [6]. Several environmental factors, including high-fat diet, are reported to activate the functioning of the hypothalamus-pituitary-adrenal axis [HPA]. Frequently evoked HPA-axis secretes excessive amount of cortisol [21] and elevated cortisol level is implicated in the development of entire spectrum of the metabolic syndrome, including insulin resistance, visceral obesity and dyslipidemia as well as the kinds of [21]. Cinnamon contains biologically active substances that have demonstrated insulin-mimetic properties. In vitro [3] and in vivo [1, 20] studies have shown that cinnamon enhances glucose uptake by activating insulin receptor kinase activity, autophosphorylation of the insulin receptor, and glycogen synthase activity. Other recent studies have demonstrated the ability of cinnamon to reduce lipid levels in fructose-fed rats, potentially via inhibiting hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity [2]. Adiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone,playing a central role in glucose and lipid metabolism [7] Furthermore, adiponectin levels are inversely associated with visceral adiposity [15]. Moreover, adiponectin has been reported to exhibit anti-atherosclerotic and anti-inflammatory effects [17,16].

High levels of dietary fat impair glucose homeostasis in rainbow trout

This study was designed to assess the effects of dietary fat levels on glucose homeostasis in rainbow trout under prolonged hyperglycaemia induced by high carbohydrate intake. Trout were fed identical amounts of one of two iso-energetic diets containing either a low (LFD, 3%) or a high fat level (HFD, 20%) and similar amounts of digestible carbohydrates (26-30%) for 14 days. While a single high fat meal reduced glycaemia compared with a low fat meal, the consumption of a high fat diet for 14 days resulted in prolonged hypergylcaemia and reduced plasma glucose clearance in response to an exogenous glucose or insulin challenge. The hyperglycaemic phenotype in trout was characterised by a reduction of the activities of lipogenic and glucose phosphorylating enzymes with a concomitant stimulation of enzymes involved in glucose production in the liver and reduced glycogen levels in the white muscle. Impaired glucose tolerance (IGT) was further associated with a significant reduction of insulin receptor substrate 1 (IRS1) protein content in muscle, and with a poor response of HFD fed fish to an exogenous insulin load, suggestive of impaired insulin signalling in trout fed with a HFD. To our knowledge, this is the first study showing that a teleost can also develop a high fat-induced IGT, characterised by persistent hyperglycaemia and reduced insulin sensitivity, established symptoms of IGT and the prediabetic insulin-resistant state in mammals. Our results also provide evidence that persistent hyperglycaemia after a high carbohydrate meal stems from a metabolic interaction between dietary macronutrients rather than from high carbohydrate intake alone.

Deficiency of MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain

Acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) is thought to be crucial for dietary fat absorption. Indeed, mice lacking the enzyme (Mogat2(-/-)) are resistant to obesity and other metabolic disorders induced by high-fat feeding. However, these mice absorb normal quantities of fat. To explore whether a high level of dietary fat is an essential part of the underlying mechanism(s), we examined metabolic responses of Mogat2(-/-) mice to diets containing varying levels of fat. Mogat2(-/-) mice exhibited 10-15% increases in energy expenditure compared with wild-type littermates; although high levels of dietary fat exacerbated the effect, this phenotype was expressed even on a fat-free diet. When deprived of food, Mogat2(-/-) mice expended energy and lost weight like wild-type controls. To determine whether MGAT2 deficiency protects against obesity in the absence of high-fat feeding, we crossed Mogat2(-/-) mice with genetically obese Agouti mice. MGAT2 deficiency increased energy expenditure and prevented these mice from gaining excess weight. Our results suggest that MGAT2 modulates energy expenditure through multiple mechanisms, including one independent of dietary fat; these findings also raise the prospect of inhibiting MGAT2 as a strategy for combating obesity and related metabolic disorders resulting from excessive calorie intake.

High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations

BackgroundAdiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. In addition, it increases fatty acid oxidation in the muscle and potentiates insulin inhibition of hepatic gluconeogenesis. Two adiponectin receptors have been identified: AdipoR1 is the major receptor expressed in skeletal muscle, whereas AdipoR2 is mainly expressed in liver. Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia; of note, all of these features are shared by the condition of insulin resistance. Although it has been shown that glucocorticoids inhibit adiponectin expression in vitro and in vivo, little is known about the regulation of adiponectin receptors. The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues.ResultsFeeding of a high-fat diet increased serum glucose levels and decreased adiponectin and adipoR2 mRNA expression in subcutaneous and retroperitoneal adipose tissues, respectively. Moreover, it increased both adipoR1 and adipoR2 mRNA levels in muscle and adipoR2 protein levels in liver. Adrenalectomy combined with the synthetic glucocorticoid dexamethasone treatment resulted in increased glucose and insulin levels, decreased serum adiponectin levels, reduced adiponectin mRNA in epididymal adipose tissue, reduction of adipoR2 mRNA by 7-fold in muscle and reduced adipoR1 and adipoR2 protein levels in muscle. Adrenalectomy alone increased adiponectin mRNA expression 3-fold in subcutaneous adipose tissue and reduced adipoR2 mRNA expression 2-fold in liver.ConclusionHyperglycemia as a result of a high-fat diet is associated with an increase in the expression of the adiponectin receptors in muscle. An excess of glucocorticoids, rather than their absence, increase glucose and insulin and decrease adiponectin levels.

Differential association of adipophilin and TIP47 proteins with cytoplasmic lipid droplets in mouse enterocytes during dietary fat absorption

Recently, we found that enterocytes dynamically store triglycerides (TGs) in cytoplasmic lipid droplets (CLDs) during dietary fat absorption. A dynamic pool of TG in the form of CLDs which expands and depletes relative to time post dietary fat challenge is present in the absorptive cells of the small intestine, enterocytes. To identify cellular factors which may play a role in the regulation of this dynamic process we investigated the expression and localization of a lipid droplet associated protein family, PAT proteins, in enterocytes of mice chronically and acutely challenged by dietary fat. We found that adipophilin and Tip47 are the only PAT genes present in mouse intestinal mucosa and both genes are present at higher levels after high-fat challenges. We found TIP47 protein present in the intestine from chow and high-fat challenged mice; however, adipophilin protein was only present after high-fat challenges. In addition, TIP47 protein level was higher after an acute than a chronic high-fat challenge whereas adipophilin protein level was higher after a chronic than an acute high-fat challenge. We co-imaged TG in CLDs using CARS microscopy and TIP47 or adipophilin using immunocytochemistry in isolated enterocytes from mice challenged chronically and acutely by high levels of dietary fat. TIP47, but not adipophilin, coats CLDs in enterocytes after an acute high-fat challenge suggesting that TIP47 plays a role in the synthesis of CLDs from newly synthesized TG at the beginning of the process of dietary fat absorption in enterocytes. Adipophilin, on the other hand, coats CLDs only in enterocytes of chronic high-fat fed mice suggesting that adipophilin may play a role in the stabilization of TG stored in CLDs in longer term. These results suggest distinct roles for TIP47 and adipophilin in dietary fat absorption.

Effects of dietarycisandtransunsaturated and saturated fatty acids on the glucose metabolites and enzymes of rats

The aim of the present study was to examine whether the level of dietary cis fatty acid (cFA), or the isomers (trans or cis) and/or the saturation of the fatty acids at high dietary fat levels altered the intracellular glucose metabolites and certain regulatory enzyme activities in the skeletal muscle and liver of rats. The animals were fed for 30 d on either a recommended control diet (7 % cFA, w/w) or a high-fat diet (20 % fatty acids, w/w). The high-fat diet was enriched with either cFA, trans fatty acid (tFA), a moderate proportion of saturated fatty acid (MSFA), or a high proportion of saturated fatty acid (HSFA). The most striking findings were observed in the gastrocnemius muscle with a HSFA diet. There was a significant increase in glucose-6-phosphate (306 %), glucose-1-phosphate (245 %), fructose-6-phosphate (400 %), fructose-1,6-bisphosphate (86 %), glyceraldehyde-3-phosphate (38 %), pyruvate (341 %), lactate (325 %), citrate (79 %) and the bisphosphorylated sugars as compared with the cFA diet. These changes were paralleled by an increase in muscle triacylglycerol content (49 %) and a decrease in glucose (39 %). In addition, the amount of cFA and the other types of fatty acid (i.e. tFA and MSFA) led to no great differences in glucose metabolism as compared with the respective control group. These data support the hypothesis that glucose changes induced by a HSFA diet are a multifaceted abnormality. Glucose and lactate transport and intracellular glucose metabolism could be the key biochemical defects involved in this detrimental effect on glucose metabolism.

Effects of increased dietary fat and exercise on skeletal muscle lipid peroxidation and antioxidant capacity in male rats

Elevated dietary fat increases oxidative metabolism and has been linked to increased oxidative stress, while exercise training may augment antioxidant capacity. Most studies examining oxidative stress in skeletal muscle employ extremely high levels of dietary fat and/or intense exercise training that may not adequately model human diet and activity patterns. The purpose of this study was to examine the interaction between an elevated (40% of calories) monounsaturated fat diet and a moderate-intensity exercise program similar to recommended human exercise prescriptions, on skeletal muscle oxidative stress and antioxidant defenses. Twenty-four male Sprague-Dawley rats (approximately 500 g) were randomly divided into 4 groups (n = 6/group): Standard Diet-Sedentary (SD-Sed), Standard Diet-Exercise (SD-Ex), Elevated Fat Diet-Sedentary (EFD-Sed), and Elevated Fat Diet-Exercise (EFD-Ex). The SD groups consumed 76% of calories from CHO, 14% from protein, and 10 % from fat, while the EFD groups received a diet of 46% of calories from CHO, 14% from protein, and 40 % from fat (high oleic sunflower oil). The exercise groups were progressively treadmill trained at 20 m/min, 4 days/week increasing from 15 min/day to 35 min/day by the end of 4 wks. Antioxidant adaptations associated with exercise training or an elevated fat diet individually reduced basal lipid peroxidation levels in the plantaris muscle. However, the combination of exercise plus a monounsaturated fat diet increased lipid peroxidation levels above that with either treatment alone. This suggests an exhaustion of the antioxidant capacity in the plantaris muscle when both exercise and increased dietary fat diet are combined.

The influence of dietary fat on insulin resistance.

Dietary fat has been implicated in the development of insulin resistance in both animals and humans. Most, although not all, studies suggest that higher levels of total fat in the diet result in greater whole-body insulin resistance. Although, in practice, obesity may complicate the relationship between fat intake and insulin resistance, clinical trials demonstrate that high levels of dietary fat can impair insulin sensitivity independent of body weight changes. In addition, it appears that different types of fat have different effects on insulin action. Saturated and certain monounsaturated fats have been implicated in causing insulin resistance, whereas polyunsaturated and omega-3 fatty acids largely do not appear to have adverse effects on insulin action. Given the importance of insulin resistance in the development of diabetes and heart disease, establishing appropriate levels of fat in the diet is an important clinical goal.

Reduction in Dietary Nutrient Density Aids in Utilization of High Protein Cottonseed Meal in Broiler Diets

This trial was conducted to determine if the reduction in weight gains and feed intake observed for broilers fed 30% cottonseed meal diets was associated with the high fat level of the diets necessary to maintain the diets isocaloric compared to corn-soybean meal control diets. Three series of energy levels were formulated to contain 2950/3000, 3000/3050, 3050/3100 ME Kcal/kg with values representing the starter/grower (S/G) dietary energy values, respectively. Within each energy series, diets were formulated to contain either soybean meal as the primary protein source (0% CSM) or 30 % cottonseed meal (30 % CSM). Male broilers were fed starter diets 0 to 21 days followed by grower diets to 42 days. At the end of the trial, six birds per pen were processed to determine carcass and parts yield. Results showed that 21 and 42 days body weights, feed consumption and mortality of the birds receiving the 30 % CSM diets were comparable to the performance of birds receiving the 0% CSM diet for the similar energy series. There was an interaction effect for 21 days feed conversion with the feed conversion of the 0% CSM 3000/3050 series significantly lower than all of the other conversion rates. Feed conversion rates at 21 and 42 days were significantly depressed for the birds receiving the 30 % CSM diets. Although the dressing percentage was lower for the 30 % CSM birds, abdominal fat was also lower and breast meat yield equaled the 0 % CSM birds. Increasing the dietary energy level increased abdominal fat. The results indicated that the high dietary fat levels used in previou s experiments could to be interfering with optimum usage of a 30 % CSM diet for growth but not for feed conversion.

Spin trapping evidence for alcohol-associated oxidative stress 1,2

The spin trapping method combined with EPR spectroscopy has been employed by a number of laboratories to study alcohol-induced oxidative stress. Ethanol is converted to a free radical metabolite, the 1-hydroxyethyl radical in chemical reactions that generate hydroxyl radicals, in incubations of rat liver microsomes and in vivo. Furthermore, both acute and chronic ethanol administration leads to formation of radicals in the liver that are presumed to be products of lipid peroxidation. In general, overall radical production is enhanced by treatments known to be involved in alcoholic liver injury, such as chronic alcohol administration along with high levels of dietary fat.

High Dietary Fat Intake Increases Renal Cyst Disease Progression in Han:SPRD-cy Rats

The effect of a high level of dietary fat on renal cyst disease was examined in the Han:SPRD-cy rat model of polycystic kidney disease. Control and diseased rats at 4 wk of age were fed either a low fat or high fat diet (5 or 20 g/100 g diet) for 6 wk. In rats with kidney disease fed the high fat rather than the low fat diet, kidneys were 17% larger, renal fluid content was 19% higher and cyst scores were 30% higher, indicating greater disease progression. In diseased rats fed the high fat diet, serum urea was 25% higher, indicating worsened renal function. Serum creatinine was 49% higher only in males. To examine whether high dietary fat worsened renal cyst disease by altering sex hormone concentrations, serum testosterone and estrogen concentrations were determined. In normal compared with diseased male rats, serum testosterone concentrations were one to three times higher. Serum testosterone concentrations were higher in normal male rats fed the high compared with the low fat diet, but were not affected by diet in diseased rats. Serum estrogen concentrations were unaffected by dietary fat levels or by disease state. Although it remains to be elucidated how dietary fat influences sex hormone concentrations in this disease, the current study demonstrates that a high dietary fat intake increases kidney disease progression in Han:SPRD-cy rats.

Saponins and phenolic content in plant dietary additives of a traditional subsistence community, the Batemi of Ngorongoro District, Tanzania

Reports of plants added to milk and meat-based soups by the Maasai and Batemi in East Africa support a role for phenolic antioxidants and hypocholesterolemic agents in the diet, and provide explanation of the low incidence of cardiovascular disease of populations that traditionally consume high levels of dietary fat and cholesterol. Plant food additives used by the Batemi of Ngorongoro District, Tanzania, were tabulated, based on interviews with 22 informants, while 17 specimens were collected in the field and analyzed for saponin and phenolic content. A total of 81% of the Batemi additives and 82% of those known to be used by the Maasai contain potentially hypocholesterolemic saponins and/or phenolics.

Influence of dietary factors on actinically-induced skin cancer

The first indication that high dietary fat intake could influence the development of ultraviolet (UV) radiation-induced skin cancer in experimental animals was reported in 1939. In the 1980s a series of animal studies showed that a high level of dietary fat intake markedly shortened the time between UV exposure and tumor appearance and increased the number of tumors that developed. Further, high levels of dietary fat affected skin cancer development at the promotional stage of UV-carcinogenesis, i.e., after the cancer causing dose of UV had been delivered. Perhaps more important, switching from a high-fat to a low-fat diet immediately after delivery of the UV-initiating dose negated the exacerbating effect of high fat intake. The latter finding suggested that dietary modification, even after a cancer-causing exposure to UV, might represent a potentially important intervention strategy in the prevention of non-melanoma skin cancer (NMSC) and provided the rationale for undertaking a dietary intervention trial. One hundred and fifteen skin cancer patients completed the 2-year clinical trial on the effect of a low-fat diet on occurrence of actinic keratosis (AK) and NMSC. Patients were randomly assigned to either continue their usual diet (control group, NI) or to adopt a diet with 20% of total caloric intake as fat (diet intervention group, DI). All patients were examined at 4-month intervals for new AK and NMSC. At baseline, the mean percent of caloric intake as fat was 40±4% in the NI group and 39±3% in the DI group. After 4 months of dietary therapy, the percent calories as fat had decreased to 21±7% in the DI group. The percent of calories as fat in the NI group did not drop below 37% during the study period. The cumulative number of new AK per patient from months 4 through 24 was 11.6±17 in the NI group and 3.2±6 in the DI group ( P<0.001). Numbers of new NMSC were analyzed in 8-month periods. There were no significant changes in NMSC occurrence in the NI group. However, NMSC occurrence in the DI group declined significantly ( P<0.02) in the last 8-month period. Patients in the DI group also had significantly ( P<0.01) fewer NMSC in the last 8-month period than did patients in the NI group (0.02 versus 0.26). Practical dietary advice, with respect to reduction of percent of calories as fat, could make an important contribution to the prevention and management of AK and NMSC.

A diet rich in coconut oil decreases the expression of retinoic acid and triiodothyronine nuclear receptors in rat liver

A considerable part of the total energy consumed by western populations is accounted for by lipids and particularly by lipids containing saturated fatty acids. A high level of dietary fat induces a lipid status characterized by a changing fatty acid profil which, in turn, could affect several hormonal actions. Thus, the aim of this study was to explore the effect of a high fat diet rich in saturated fatty acids on the expression of nuclear receptors of retinoic acid (RAR) and triiodothyronine (TR) in rat liver. This expression was mainly evaluated as binding properties of RAR and TR (evaluated by an isotopic displacement analysis), and quantitation of mRNAs of these receptors (using a semi-quantitative RT-PCR method). Following seven weeks of a diet containing 30% coconut oil and 5% olive oil, the maximum binding capacity of RAR and TR was decreased by 36% and 23%, respectively (the apparent affinity of the receptors was not affected). The abundance of mRNAs of these receptors was also lowered (by approximately 37–40%), suggesting that the decreased number of receptors results from a mechanism occuring, at least in part, at a transcriptional level.

Immunobiology of lipid-modulated UV-carcinogenesis

Previous studies have demonstrated that high levels of dietary fat exacerbate UV-carcinogenic expression and suppress immunoresponsiveness. The latter may account for the former response. We have explored this possibility through T-lymphocyte transfer studies. Groups of HRA.HRII-c/ + /Skh hairless mice were fed isocaloric diets containing high (12%, wt./wt.) or low (0.75%) levels of corn oil and irradiated 5 days/week (1.0 J cm −2/day) for 11 weeks with filtered FS-40 sunlamps. At weeks nine and 12, enriched T-cells from high-fat donors that had received 11 weeks of UV were transferred intravenously to low-fat recipients. Median tumor times for high-fat, low-fat recipient, and low-fat groups were 15.8, 18.5, and 21.6 weeks, respectively. The significantly ( P<0.03) shortened primary tumor latent period in low-fatfed animals resulting from transfer of relatively low levels of T-cells derived from chronically irradiated high-fat donors demonstrates that the influence of dietary fat upon UV-carcinogenic expression is, at least partially, mediated via immunologic mechanisms. Further studies suggest that fat-modulated carcinogenesis can, itself, be regulated immunologically. A soluble T-14 (mouse squamous carcinoma cell line) cell-free fraction was injected subcutaneously at axillae and inguen of animals fed the high-fat diet during the first three weeks of UV or immediately post-UV. At week four post-UV, animals were challenged with T-14 cells injected subcutaneously at both flanks. 21 days post-challenge the tumor volumes of low-fat and high-fat immunized animals were zero versus 593 mm 3 for the high-fat group ( P < 0.007). Such treatment significantly ( P< 0.03) increases the latent period of UV-induced primary tumors as well, when compared to non-treated high-fatfed animals.

Role of adiposity in food intake control of juvenile chinook salmon ( Oncorhynchus tshawytscha)

Experiments were conducted to determine if adiposity affected feed intake in juvenile chinook salmon ( Oncorhynchus tshawytscha) with different nutritional histories. Fry were fed high-fat (23%) or low-fat (3%) diets at high (satiation) and low (one-half satiation) ration levels for 7 months before the start of the intake experiment. This pre-treatment produced fish averaging 22 g with 11.3% (high-fat diet) and 5.4% (low-fat diet) body fat when fed to satiation or 11 g with 7.0% (high-fat diet) and 3.3% (low-fat diet) body fat when fed at one-half satiation. Experiment 1 had a 2 × 2 factorial design where duplicate groups of 20 fish from the high-ration groups (22 g) were fed high- (16%) or low- (4%) fat diets twice daily to satiation 6 days/wk for 3 weeks. Daily feed intake was recorded. The same protocol was used in experiment 2 on fish (40 fish per tank) from the smaller low-ration groups (11 g). Feed intakes on day 1, cumulative feed intakes after 21 days and plasma levels of insulin and insulin-like growth factor 1 (IGF-1) were compared using two-way ANOVA with initial whole body fat and dietary fat as the independent variables. In both experiments, high body fat led to significantly lower feed intake on day 1 and after 21 days of feeding. High dietary fat levels caused greater intake on day 1, but by the end of the experiments, this effect was not significant, suggesting some adaptation to the diets. Insulin in plasma showed greater response to dietary fat (high-fat diets causing higher insulin levels), whereas IGF-1 responded more to body fat level (high body fat led to higher IGF-1 levels). Our results show that in both-fast- and slow-growing juvenile chinook salmon, adiposity plays a role in regulation of feed intake and that adiposity appears to interact with IGF-1. Dietary fat levels had transient effects on intake, but plasma insulin levels consistently reflected the dietary fat levels. An important implication of our findings is that food intake, and possibly growth, could be retarded if a feeding regime results in high body fat levels.

Spin Trapping Studies of Alcohol-Initiated Radicals in Rat Liver: Influence of Dietary Fat

We conducted spin trapping experiments to test the effects of acute and chronic alcohol consumption in livers from rats that had been fed either high fat (35% of energy) or low fat (12% of energy) liquid diets. Rats were anesthetized with isoflurane, the spin trapping agent POBN [α-(4-pyridyl-1-oxide)-N-t-butylnitrone] was administered by intravenous injection, and bile samples were collected for electron paramagnetic resonance (EPR) analyses. Two different types of EPR spectra were observed in bile from the animals in these studies. One set of spectral lines was from the 1-hydroxyethyl radical adduct of POBN, which was conclusively identified by injecting the rats with [1-13C]ethanol. The EPR signals of a second type of radical adduct in bile could be observed both before and after acute administration of ethanol. Although the radical(s) responsible for this second series of signals could not be conclusively identified, it is likely that lipid radicals were formed under these conditions and trapped by POBN. For both types of radical adducts, the most intense EPR signals were observed in rats that had been fed alcohol in combination with a high fat diet for 2 wk before the experiments. These results confirm and extend previous data indicating that high levels of dietary fat enhance alcohol-associated free radical formation in the liver.