Adaptive response of rat pancreatic lipase to dietary fat: effects of amount and type of fat

Pancreatic lipase adapts to changes in dietary fat by parallel changes in synthesis. The adaptation to changes in type of dietary fat (saturation or chain length) is unclear. The effects of changes in amount and type of dietary fat were examined in weanling rats fed for 1 wk diets low in fat (LF) with 10% kcal as corn oil, moderate in fat (MF) with 40% kcal as fat (corn oil, lard, safflower oil, butter, olive oil or coconut oil), or high in fat (HF) with 67% kcal as fat (as for MF). Growth was comparable among rats fed these diets. Pancreatic lipase activity increased in all HF diets (180%) compared to the LF diet. In MF diets, only the highly unsaturated safflower oil increased pancreatic lipase (162%) compared to the LF diet. Food consumption varied, but was not related to the response of pancreatic lipase. When weanling rats were fed diets with 11, 40, 47, 54, 67 and 75% kcal as corn oil, pancreatic lipase activity was not stimulated at or below 47% kcal fat, but was maximally stimulated (twofold) by 54 or 67% fat. These findings suggest that pancreatic lipase activity adapts primarily to the amount of dietary fat and responds to the type of fat only below the threshold level of dietary fat (47% kcal).     

Dietary modulation of epidermal growth factor action in cultured pancreatic acinar cells of the rat

The effects of epidermal growth factor (EGF) and its interaction with dietary adaptation were examined in pancreatic acinar cells isolated from rats fed for 1 wk diets with 67% kcal as fat (HF), 67% kcal as carbohydrate (HC), or unrefined, closed formula diet (UD). Cells were cultured for 48 h in serum-free medium containing 4.2 nM (control), 42 pM, 0.42 nM or 42 nM EGF. EGF at the concentrations tested did not affect cellular protein, DNA, amylase and lipase. In freshly isolated and cultured cells, specific activity of intracellular phenylalanine was affected by diet with the highest specific activity in HF cells, but was not affected by EGF. In freshly isolated cells, EGF increased the rate of phenylalanine incorporation into cellular protein only in HF cells at 42 nM. In cultured cells, EGF biphasically increased phenylalanine incorporation at 42 pM and 42 nM in UD and HC cells, but only increased phenylalanine incorporation in HF cells at 42 nM. These data suggest that diet can alter the response of pancreatic acinar cells to EGF. Dietary alterations of cellular responsiveness to regulatory peptides may participate in pancreatic regulation and dietary adaptation in vivo.     

Effects of manganese deficiency and dietary composition on rat pancreatic enzyme content

Recent studies show that manganese (Mn) deficiency increases pancreatic amylase content. Pancreatic adaptation to dietary composition also alters enzyme content. The present study investigated whether Mn deficiency alters pancreatic adaptation to diet. Weanling rats that were fed for 6 wk a high carbohydrate (HC) diet with less than 1 mg Mn/kg diet (Mn deficient) or 40 mg Mn/kg diet (control) were divided into three control and deficient dietary subgroups: 1) HC, 2) high protein (HP) or 3) high fat (HF). Rats were then fed these diets for 10 d. Body weights and food consumption were comparable among the groups. Pancreatic and hepatic Mn contents were significantly lower in Mn-deficient rats than in respective controls. Digestive enzymes adapted to diet in both control and Mn-deficient rats with the greatest amylase, lipase and trypsin activities in HC, HF and HP rats, respectively. Mn deficiency resulted in significantly greater amylase activity in HC and HP groups and lipase activity in only the HF group than in respective controls. These data suggest that Mn participates in the regulation of pancreatic amylase content and in the adaptive response of pancreatic lipase to dietary fat.     

Lactation decreases pancreatic lipase mRNA level in the rat

Lactation alters maternal metabolism and increases food intake in rats to support milk production. Pancreatic lipase (PL) is primarily responsible for fat digestion in adults and is regulated by dietary fat. The present research determined the regulation of PL by lactation and dietary fat. In Expt 1, eighteen Sprague-Dawley dams and twelve age-matched virgins (controls) were fed a low-fat diet (LF; 11 % energy as safflower oil) for 7-63 d. At postpartum (day 0), peak lactation (day 15) and post-lactation (day 56) and after 7 d in virgins, the pancreas was removed for mRNA and enzyme analyses. In Expt 2, thirty-six Sprague-Dawley dams were fed LF until day 9 postpartum when dams were divided into three groups of twelve; one continued to be fed LF, one was fed a moderate-fat diet (MF; 40 % energy as safflower oil); and one was fed a high-fat diet (HF; 67 % energy as safflower oil) diet. At peak lactation (day 15) and post-lactation (day 56), the pancreas was removed for mRNA and enzyme analyses. Expt 1 revealed that lactation and post-lactation significantly (P<0.001) decreased PL mRNA (67 % and 76 %, respectively), but only post-lactation decreased PL activity. Increased dietary fat in Expt 2 significantly increased PL mRNA (LF相似文献   

A controlled high-fat diet induces an obese syndrome in rats

The prevalence of obesity is increasing. Although the etiology of obesity is complex, dietary factors, particularly the consumption of a high-fat (HF) diet, is considered a risk factor for its development. Nonetheless, a causal role of dietary fat has never been definitively documented, in part because of inadequate animal models. We developed a rat model of diet-induced obesity that will be a powerful tool for assessment of this issue. In four experiments, Long-Evans rats ate ad libitum a synthetic semipurified diet containing 20 g (HF) or 4 g [low-fat (LF)] of fat/100 g of diet or a nonpurified diet. Other rats ate ad libitum the HF diet in amounts matched to the energy intake of the LF rats. When compared over 10 wk of free feeding, HF rats weighed 10% more (P < 0.01) than LF rats and had 50% more body fat (P < 0.01), as well as significant hyperleptinemia and insulin resistance. Compared with rats fed the nonpurified diet, the HF rats had even more marked differences in these variables. The rats fed the HF diet to match the rats fed the LF diet had similar body weights but significantly more adipose tissue than LF rats, suggesting that diet composition and/or energy density of the diet affects fat deposition. This dietary regimen has reproducible effects on body size and composition, and these are similar in male and female rats. This model of diet-induced obesity will be a useful tool for studying the mechanisms by which dietary fat influences the regulation of energy balance.     

Synthesis of amylase by cultured rat pancreatic acinar cells: effects of antecedent diet

Amylase synthesis in cultured pancreatic acinar cells was determined using an affinity adsorbent, alpha-glucohydrolase inhibitor--Sepharose 4B. This adsorbent exhibited a consistent binding capacity and was specific for amylase. To assess the effects of antecedent diet on amylase synthesis during culture, acinar cells from rats fed high fat (HF) or high carbohydrate (HC) diets for 7 d were cultured for 1-48 h in serum-free medium. Amylase activity remained significantly higher in cells from rats fed the HC diet than in cells from rats fed the HF diet through 24 h in culture, despite an overall decrease with time in culture. The relative synthesis of amylase [([3H]phenylalanine amylase/[3H]phenylalanine total protein) x 100] was also significantly higher in cells from HC-fed rats than in cells from HF-fed rats at isolation and remained higher during culture. The results demonstrate that these cultured acinar cells synthesize amylase in vitro and that the effect of diet on amylase activity and relative synthesis persists during culture.     

Adaptation of lingual lipase to dietary fat in rats

To study the adaptive response of lingual lipase and pancreatic lipase to dietary fat, three sets of experiments were performed in adult male rats. In the first experiment, rats were fed for 3 wk a low fat diet (4.5% fat) or a 10, 20 or 30% fat diet. In the second, rats were fed a 4.5% fat diet for 4 wk or a 20% fat diet for 1, 2 or 4 wk. In the third, rats were fed for 3 wk a 10% fat diet with various sources of fat (lard, sunflower oil, olive oil, peanut oil, butter, soybean oil, corn oil or salmon oil). The results demonstrated that 10% dietary fat was sufficient to promote a maximum significant increase in lingual lipase activity (expressed in units/g tissue and in units/mg protein), whereas pancreatic lipase responded steadily to 20 and 30% fat diets. After 1 wk of feeding 20% dietary fat, both enzyme specific activities had reached their maximum values. The fatty acid composition of dietary triglyceride molecules (chain length, number and location of double bonds) had no specific effect on the adaptation of lingual lipase. The physiological implications of these findings are discussed in regard to the role of intragastric lipolysis in fat digestion.     

Insulin action in rats is influenced by amount and composition of dietary fat

The chronic influence of dietary fat composition on obesity and insulin action is not well understood. We examined the effect of amount (20% vs 60% of total calories) and type (saturated vs polyunsaturated) of fat on insulin action and body composition in mature male rats. Six months of feeding a high fat (HF) diet led to obesity and impaired insulin action (determined by a euglycemic-hyperinsulinemic clamp), neither of which were reversed by a subsequent 6 months of feeding a low fat (LF) diet. Within HF fed rats, type of fat did not affect body composition or insulin action. Six months of feeding a low fat diet led to only a slight decline in insulin action, with no difference due to type of dietary fat. From 6-9 months, insulin action became more impaired in LF rats fed the saturated diet than in LF rats fed the polyunsaturated diet. By 12 months, all groups were obese and had a similar impairment in insulin action. The amount and type of fat in the diet did not influence the overall degree of impairment in insulin action but did affect the time course. Both feeding a high fat diet and feeding a low fat saturated diet accelerated the impairment in insulin action relative to rats fed a low fat polyunsaturated fat diet.     

Saponins from platycodi radix ameliorate high fat diet-induced obesity in mice

We examined the effects of crude saponins isolated from Platycodi radix on the degree on fat storage induced in mice by feeding a high fat diet for 9 wk. We reported previously that feeding mice a high fat diet for a longer time caused obesity and fatty liver compared with those fed a low fat diet, nonpurified diet. Feeding a high fat diet containing 10 or 30 g/kg crude saponins prevented the body and parametrial adipose tissue weight increases and hepatic steatosis of mice fed the high fat diet alone. Furthermore, crude saponins (375 mg/kg) inhibited the elevations in blood triacylglycerol in rats orally administered a lipid emulsion compared with that of rats given the lipid emulsion alone. Previously, we reported that crude saponins inhibited pancreatic lipase activity in vitro. To identify the active substance(s) of crude saponins, we examined the effects of purified platycodin D, the primary saponin in the crude mixture, on pancreatic lipase activity and on the blood triacylglycerol elevation in rats administered the oral lipid emulsion tolerance test. Platycodin D (0.5 and 1.0 g/L) inhibited pancreatic lipase activity in vitro and at a dose of 244 mg/kg, inhibited the elevation of blood triacylglycerol. Therefore, the antiobesity effect of the crude saponins in mice fed a high fat diet may be due to the inhibition of intestinal absorption of dietary fat by platycodin D.     

Bitter melon (Momordica charantia) reduces adiposity,lowers serum insulin and normalizes glucose tolerance in rats fed a high fat diet

Bitter melon (BM) is known for its hypoglycemic effect but its effect on rats fed a hyperinsulinemic high fat diet has not been examined. In a dose-response (0.375, 0.75 and 1.5%) study, oral glucose tolerance was improved in rats fed a high fat (HF; 30%) diet supplemented with freeze-dried BM juice at a dose of 0.75% or higher (P < 0.05). At the highest dose, BM-supplemented rats had lower energy efficiency (P < 0.05) and tended (P = 0.10) to have less visceral fat mass. In a subsequent experiment, rats habitually fed a HF diet either continued to consume the diet or were switched to a HF+BM, low fat (LF; 7%) or LF+BM diet for 7 wk. BM was added at 0.75%. Final body weight and visceral fat mass of the two last-mentioned groups were similar to those of rats fed a LF diet for the entire duration. Rats switched to the HF+BM diet gained less weight and had less visceral fat than those fed the HF diet (P < 0.05). The addition of BM did not change apparent fat absorption. BM supplementation to the HF diet improved insulin resistance, lowered serum insulin and leptin but raised serum free fatty acid concentration (P < 0.05). This study reveals for the first time that BM reduces adiposity in rats fed a HF diet. BM appears to have multiple influences on glucose and lipid metabolism that strongly counteract the untoward effects of a high fat diet.     

Detrimental effects of a high fat diet in early renal injury are ameliorated by fish oil in Han:SPRD-cy rats

Dietary fish oils containing (n-3) fatty acids can modulate renal inflammatory injury. We previously demonstrated that a high fat (HF) diet worsens early renal disease progression in the Han:SPRD-cy rat model of polycystic kidney disease (PKD). Therefore, using HF (20 g/100 g diet) and low fat (LF; 5 g/100 g diet) diets, we compared the effects of menhaden oil (MO), soybean oil (SO) and cottonseed oil (CO) on renal function and histology in male Han:SPRD-cy rats fed the diets for 6 wk in the early stages of renal disease. Overall, rats fed HF compared with those fed LF diets had larger kidneys, more renal fibrosis and lower creatinine clearance (main effects of fat level).Rats fed MO rather than CO and SO diets had significantly lower kidney weights, kidney water content, cyst volumes and serum cholesterol and triglyceride concentrations (main effects of fat type). Rats fed MO diets also had less renal fibrosis than those fed CO diets, but the least fibrosis was in rats fed SO diets. Analysis of simple effects (due to interactions between fat level and type) revealed that HF diets increased renal inflammation in rats fed CO diets, but reduced inflammation was present in those fed SO and MO diets; HF diets also increased compared with LF diets serum urea nitrogen concentrations in rats fed the MO and CO diets, but not the SO diet. These results confirm that high dietary fat worsens early disease progression in this model of renal disease, and further demonstrate that diets with oils containing (n-3) fatty acids ameliorate some of the detrimental effects of a high fat diet.     

Dietary-induced changes in the fatty acid profile of rat pancreatic membranes are associated with modifications in acinar cell function and signalling

The effects of dietary lipids on the fatty acid composition of rat pancreatic membranes and acinar cell function were investigated. Weaning rats were fed for 8 weeks on one of two diets which contained 100 g virgin olive oil (OO) or sunflower-seed oil (SO)/kg. Pancreatic plasma membranes were isolated and fatty acids determined. Amylase secretion and cytosolic concentrations of Ca(2+) and Mg(2+) were measured in pancreatic acini. Membrane fatty acids were profoundly affected by the diets; the rats fed OO had higher levels of 18 : 1n-9 (42.86 (sem 1.99) %) and total MUFA compared with the animals fed SO (25.37 (sem 1.11) %). Reciprocally, the SO diet resulted in greater levels of total and n-6 PUFA than the OO diet. The most striking effect was observed for 18 : 2n-6 (SO 17.88 (sem 1.32) %; OO 4.45 (sem 0.60) %), although the levels of 20 : 4n-6 were also different. The proportion of total saturated fatty acids was similar in both groups, and there was only a slight, not significant (P=0.098), effect on the unsaturation index. Compared with the OO group, acinar cells from the rats fed SO secreted more amylase at rest but less in response to cholecystokinin octapeptide, and this was paralleled by reduced Ca(2+) responses to the secretagogue. The results confirm that rat pancreatic cell membranes are strongly influenced by the type of dietary fat consumed and this is accompanied by a modulation of the secretory activity of pancreatic acinar cells that involves, at least in part, Ca(2+) signalling.     

Dietary cholesterol and experimental mammary cancer development

The effect of high‐ and low‐fat diets, with and without cholesterol supplementation, on the development of N‐methylnitrosourea (NMU)‐induced mammary tumors was assessed. Diets consisting of 1. high fat (HF) (20% lard), 2. HF + cholesterol, 3. low fat (LF) (4% lard) + cholesterol, and 4. LF were fed to F344 female rats (24 animals/group) 2 days after NMU administration, and cumulative mammary tumor incidence was monitored for a total of 26 weeks. Animals fed HF diets exhibited significantly greater tumor incidences and numbers of tumors/animal than did animals fed LF diets (p < .0001), regardless of whether cholesterol was present in the diet. These results are consistent with the hypothesis that the mammary‐tumor promoting effects of HF diets are exerted primarily by the triglyceride fraction rather than by the nonsaponifiable (sterol) fraction of total dietary fat.     

Effects of changing dietary fat content on plasma gut hormone concentrations in diet-induced obese and diet-resistant rats

Gut hormones play key roles in the regulation of energy homeostasis. However, little is known about the long- and short-term effects of changing dietary fat content on gut hormones. We aim to examine the effects of changing dietary fat content on plasma gut hormone concentrations in diet-induced obese (DIO) and diet-resistant (DR) rats. After inducing obesity with a high-fat (HF) diet, male Sprague-Dawley rats were divided into three groups according to their body-weight gain: DIO; DR; control (CON). The DIO and DR rats were further divided in random into two groups. One continued on a HF diet and the other switched to a low-fat (LF) diet for an additional 4 weeks. Finally, each group was randomly divided into three subgroups (n 8): fasted; fasted-refed HF; fasted-refed LF diet groups. Replacing a HF diet with a LF diet for 4 weeks resulted in less fat mass, higher fasting and post-HF plasma ghrelin concentration and lower postprandial plasma cholecystokinin concentration in the DIO and DR rats. Acute switching dietary fat resulted in significantly higher post-HF plasma ghrelin concentrations than post-LF ghrelin concentrations in the DR rats on LF diet (DRLF) and DIO rats on LF diet (DIOLF) rats, and significantly higher post-HF obestatin concentrations than post-LF obestatin concentrations in the CON, DR rats on HF diet (DRHF) and DRLF rats. Dietary fat content appears to play a role in the gut hormone profile, which may consequently influence fat mass.     

Effects of dietary pectin and fat on the small intestinal contents and exocrine pancreas of rats

The effects of dietary pectin and fat level on digestive enzyme activities in the pancreas and small intestine and on intestinal bile acid levels were investigated. In unfed rats, dietary pectin did not influence the pancreatic enzymes studied, but a higher level of corn oil in the diet lowered the amylase activity in the pancreas, increased pancreatic lipase activity and slightly lowered the chymotrypsin and trypsin activities. Diet did not change the dry weight of the pancreas. In the fed rats, dietary pectin increased the dry weight of the small gut wash plus the mucosal scraping. Dietary pectin increased the small intestinal lipase and chymotrypsin levels and at the low level of fat only, increased amylase and trypsin activities in the small intestine of fed rats. Intestinal lipase levels were higher and amylase levels lower in rats consuming the high level of corn oil. These results indicate that changes in dietary fat level led to changes in the amylase and lipase content of secreted pancreatic juice and that differences in absorption associated with diets containing pectin could be the result of increased material in the small intestine.     

Effects of feeding fat during pregnancy and lactation on growth performance, milk composition and very low density lipoprotein composition in ratstc "density lipoprotein composition in rats"

The effects of dietary fat during pregnancy and lactation on growth performance of pups, milk composition and very low density lipoprotein composition in rats were studied. A total of 33 dams were used in this study and each litter was adjusted to 8 pups per dam. The dams were fed on high fat (150 g fat/kg diet, HF), medium fat (75 g fat/kg of diet, MF) and low fat (2.5 g fat/kg diet, LF) diets. The body weights of dams increased during pregnancy and decreased after pregnancy. The HF pups had a higher body weight and higher weight gain than those of LF pups. The amount of feed intake of HF dams was significantly higher than LF and MF dams. The HF dams had significantly higher milk fat and water concentrations than LF dams. The milk protein was not significantly different among the treatment groups. All dams showed hypertriacylglycerolaemia in their very low density lipoprotein (VLDL) in late pregnancy. The VLDL-protein concentrations increased during the first week after parturition. The HF dams showed a greater response to the dietary fat than that of LF and MF dams. The findings suggest that addition of fat in the diet during pregnancy and lactation may improve the milk quality through modifying the composition of VLDL contents, leading to better growth of pups.     

Diurnal changes in plasma and liver lipids and lipoprotein lipase activity in heart and adipose tissue in rats fed a high and low fat diet

In order to evaluate a) the respective roles of adipose and muscle lipoprotein lipase (LPL) in the clearing of alimentary lipemia and b) the role of the resulting nonesterified fatty acids (NEFA) in controlling hepatic ketogenesis and liver triglyceride content, a number of parameters related to lipid metabolism were studied over the 24 hour period (the dark period being from 1930 to 0730 hours), in rats ad libitum fed either a low-fat (LF) or a high-fat (HF) diet containing respectively 1.1% and 41.5% lard. During spontaneous feeding (from 1500-1800 hours onwards), LPL activity in LF rats increased in adipose tissue and decreased in heart; in rats fed the HF diet for 3 weeks, the postprandial rise in adipose LPL was smaller and there was no decrease in heart LPL before 2100 hours. In HF rats, unlike the LF, feeding resulted in a large increase in circulating NEFA and total ketone concentrations, an increase in liver beta-hydroxybutyrate dehydrogenase activity, and a decrease in hepatic triglyceride content. The findings clearly indicate that in HF rats, muscle LPL controls the postprandial rise in plasma NEFA concentrations, which in turn appear to determine the extent of ketonemia and liver triglyceride changes. The possible control of these metabolic events by insulin is discussed.     

Body fat deposition: effects of dietary fat and two exercise protocols.

We evaluated the effects of two levels of dietary fat (0 and 20g beef tallow/100g diet) and two treadmill exercise protocols (low-intensity, high-intensity) on fat deposition in rats.

Male Wistar rats (n = 50) remained sedentary or were forced to run 840 meters/day, 5 days/week, on a rodent treadmill. Those on the high-intensity protocol covered this distance in less time (38 min) than those on the low-intensity program (60 min). Responses to high-fat (HF) and low-fat (LF) diets were compared within each exercise group for this 8-week study.

High fat feeding, as a single factor, did not affect energy intake, carcass fat, intramuscular fat, or fat associated with any tissue studied. The HF diet also did not affect responses to either exercise protocol. The high-intensity-exercised animals had less carcass fat (LF: 21% less; HF: 33% less), smaller omental fat pads (LF: 20% less; HF: 37% less), and retroperitoneal fat pads (LF: 19% less; HF: 38% less), and lower serum triglyceride levels (LF: 26% less; HF: 41% less) than sedentary rats. Those differences were less marked for the low-intensity-exercise rat. Neither mode of exercise or diet affected lipid concentrations in hindlimb muscles, livers, hearts, or kidneys.

Exercised animals generally had less fat deposition than sedentary rats but this was more pronounced for high-intensity than low-intensity-exercised rats, and was not affected by feeding a 20% beef tallow diet.     

Insulin insensitivity is rapidly reversed in rats by reducing dietary fat from 40 to 30% of energy.

The objective of this study was to determine the effect of reducing dietary fat content from 40 to 30% of total energy on body composition and insulin sensitivity in rats. Female Sprague-Dawley rats were fed either a control diet (30% energy as fat) or a high fat diet (40% energy as fat) for 10 wk. In vivo glucose tolerance tests indicated that both basal and glucose-stimulated insulin concentrations were elevated in rats fed the high fat diet. Two groups of rats offered the high fat diet were then fed the control diet (HF,C) and two that had received the high fat diet were then fed a diet (30% energy as fat) containing a fat-mimetic carbohydrate (HF,M). Two groups continued to receive the high fat diet and two groups continued to receive the control diet. Rats were killed 1 and 2 wk after the diet switch. In vivo glucose tolerance tests indicated that insulin sensitivity was corrected in HF,C and HF,M rats after 3 d. Body fat content was greater in rats fed the high fat diet and remained high after 7 d of consuming either diet with 30% of energy from fat. There was no effect of diet on liver fatty acid utilization or on diaphragm glucose oxidation. Adipocytes from all treatment groups were insulin resistant, possibly due to feeding status or age of the rats. The results of this study suggest that a moderate reduction in fat intake, from 40 to 30% of energy, can produce a rapid improvement of insulin sensitivity in insulin-insensitive rats, independent of changes in body fat content and irrespective of the means used to reduce dietary fat content.