Foraging on anthropogenic food predicts problem-solving skills in a seabird.

Species and populations with greater cognitive performance are more successful at adapting to changing habitats. Accordingly, urban species and populations often outperform their rural counterparts on problem-solving tests. Paradoxically, urban foraging also might be detrimental to the development and integrity of animals' brains because anthropogenic foods often lack essential nutrients such as the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are important for cognitive performance in mammals and possibly birds. We tested whether urbanization or consumption of EPA and DHA are associated with problem-solving abilities in ring-billed gulls, a seabird that historically exploited marine environments rich in omega-3 fatty acids but now also thrives in urban centres. Using incubating adults nesting across a range of rural to urban colonies with equal access to the ocean, we tested whether urban gulls preferentially consumed anthropogenic food while rural nesters relied on marine organisms. As we expected individual variation in foraging habits within nesting location, we characterized each captured gulls' diet using stable isotope and fatty acid analyses of their red blood cells. To test their problem-solving abilities, we presented the sampled birds with a horizontal rendition of the string-pull test, a foraging puzzle often used in animal cognitive studies. The isotopic and fatty acid profiles of urban nesters indicated a diet comprising primarily anthropogenic food, whereas the profiles of rural nesters indicated a high reliance on marine organisms. Despite the gulls' degree of access to urban foraging habitat not predicting solving success, birds with biochemical profiles reflecting anthropogenic food (less DHA and a higher carbon-13 ratio in their red blood cells) had a greater probability of solving the string-pull test. These results suggest that experience foraging on anthropogenic food is the main explanatory factor leading to successful problem-solving, while regular consumption of omega-3s during incubation appears inconsequential.

Treatment of preadipocytes with fish oil, mixed oil, or soybean oil-based lipid emulsions have differential effects on the regulation of lipogenic and lipolytic genes in mature 3T3-L1 adipocytes.

The key adipose tissue characteristics are established during early development, where lipids play an essential role. Lipid emulsions used in total parenteral nutrition have different omega-(n) 6 to n-3 fatty acid ratios. A lower n-6:n-3 fatty acid decreases lipid accumulation; however, the effects of lipid emulsions with different n-6 to n-3 fatty acid ratios on the programming of preadipocytes to affect lipid accumulation in mature adipocytes is not known. This study compared the effects of Fish oil (FO), Mixed oil (MO), and Soybean oil (SO) based lipid emulsion on genes involved in adipogenesis, lipogenesis, lipolysis, and ß-oxidation in 3T3-L1 adipocytes. Preadipocytes were treated with specific lipid emulsions and then differentiated to mature adipocytes in the absence of lipid emulsions. In a separate experiment, mature 3T3-L1 adipocytes were treated with lipid emulsions to investigate the effects on genes involved in lipolysis. Fatty acid composition, triacylglycerol levels, and the mRNA expression of genes involved in adipogenesis, lipogenesis, lipolysis, and ß-oxidation were measured. Preadipocytes and mature adipocytes treated with FO showed higher incorporation of n-3 polyunsaturated fatty acids, lower triacylglycerol levels, and decreased mRNA expression of adipogenic and lipogenic genes, followed by MO and SO. FO and MO increased the mRNA expression of carnitine palmitoyltransferase-1, while FO decreased the mRNA expression of lipolytic genes compared to untreated cells. Our findings suggest that FO programs preadipocytes to prevent adipose tissue dysfunction in mature adipocytes; the effects of FO-based lipid emulsion were followed by MO and SO.

Maternal omega-3 fatty acids maintained positive maternal lipids and cytokines profile, and improved pregnancy outcomes of C57BL/6 mice.

Omega (n)-3 polyunsaturated fatty acids (PUFA) are known to regulate lipid metabolism and inflammation; however, the regulation of maternal lipid metabolism and cytokines profile by n-3 PUFA during different gestation stages, and its impact on fetal sustainability is not known. We investigated the effects of maternal diet varying in n-3 PUFA prior to, and during gestation, on maternal metabolic profile, placental inflammatory cytokines, and fetal outcomes. Female C57BL/6 mice were fed either a high, low or very low (9, 3 or 1% w/w n-3 PUFA) diet, containing n-6:n-3 PUFA of 5:1, 20:1 and 40:1, respectively for two weeks before mating, and throughout pregnancy. Animals were sacrificed prior to mating (NP), and during pregnancy at gestation days 6.5, 12.5 and 18.5. Maternal metabolic profile, placental cytokines and fetal outcomes were determined. Our results show for the first time that a maternal diet high in n-3 PUFA prevented dyslipidemia in NP mice, and maintained the expected lipid profile during pregnancy. However, females fed the very low n-3 PUFA diet became hyperlipidemic prior to pregnancy, and carried this profile into pregnancy. Maternal diet high in n-3 PUFA maintained maternal plasma progesterone and placental pro-inflammatory cytokines profile, and sustained fetal numbers throughout pregnancy, while females fed the low and very-low n-3 PUFA diet had fewer fetuses. Our findings demonstrate the importance of maternal diet before, and during pregnancy, to maintain maternal metabolic profile and fetus sustainability. These findings are important when designing dietary strategies to optimize maternal metabolism during pregnancy for successful pregnancy outcome.

Shrimp Oil Extracted from Shrimp Processing By-Product Is a Rich Source of Omega-3 Fatty Acids and Astaxanthin-Esters, and Reveals Potential Anti-Adipogenic Effects in 3T3-L1 Adipocytes.

The province of Newfoundland and Labrador, Canada, generates tons of shrimp processing by-product every year. Shrimp contains omega (n)-3 polyunsaturated fatty acids (PUFA) and astaxanthin (Astx), a potent antioxidant that exists in either free or esterified form (Astx-E). In this study, shrimp oil (SO) was extracted from the shrimp processing by-product using the Soxhlet method (hexane:acetone 2:3). The extracted SO was rich in phospholipids, n-3 PUFA, and Astx-E. The 3T3-L1 preadipocytes were differentiated to mature adipocytes in the presence or absence of various treatments for 8 days. The effects of SO were then investigated on fat accumulation, and the mRNA expression of genes involved in adipogenesis and lipogenesis in 3T3-L1 cells. The effects of fish oil (FO), in combination with Astx-E, on fat accumulation, and the mRNA expression of genes involved in adipogenesis and lipogenesis were also investigated. The SO decreased fat accumulation, compared to untreated cells, which coincided with lower mRNA expression of adipogenic and lipogenic genes. However, FO and FO + Astx-E increased fat accumulation, along with increased mRNA expression of adipogenic and lipogenic genes, and glucose transporter type 4 (Glut-4), compared to untreated cells. These findings have demonstrated that the SO is a rich source of n-3 PUFA and Astx-E, and has the potential to elicit anti-adipogenic effects. Moreover, the SO and FO appear to regulate adipogenesis and lipogenesis via independent pathways in 3T3-L1 cells.

Intraperitoneal Administration of Short-Chain Fatty Acids Improves Lipid Metabolism of Long-Evans Rats in a Sex-Specific Manner.

Short-chain fatty acids (SCFAs) are microbial metabolites, mainly generated by the action of gut microbiota on dietary fibers. Acetate, propionate, and butyrate are the three main SCFAs produced typically in a 60:20:20 molar ratio in the colon. Acetate, propionate, and butyrate, when given individually as supplements, have shown a protective role in obesity and hyperglycemia; however, the sex-specific effects of a mixture of SCFAs, when given in 60:20:20 ratio, on the regulation of lipid metabolism and lipid profile are not known. Male and female Long-Evans rats were given a mixture of SCFAs (acetate, propionate, and butyrate; molar ratio 60:20:20) each day for seven days intraperitoneally; plasma and hepatic lipids, gene expression, and lipidomics profile were analyzed. SCFAs significantly decreased plasma and hepatic triglycerides and cholesterol in males, whereas the fatty acyl composition of cholesteryl esters, triglycerides, and phospholipids was modulated in females. SCFAs decreased the mRNA expression of hepatic acetyl-CoA carboxylase-1 in both males and females. Our findings demonstrate for the first time that SCFAs (60:20:20) improved plasma and hepatic lipid levels and fatty acyl composition in a manner that may provide cardio-protective and anti-inflammatory effects in both sexes, via independent mechanisms.

Omega-3 fatty acids accelerate fledging in an avian marine predator: a potential role of cognition.

Consuming omega-3 fatty acids (n-3 LCPUFAs) during development improves cognition in mammals, but the effect remains untested in other taxa. In aquatic ecosystems, n-3 LCPUFAs are produced by phytoplankton and bioaccumulate in the food web. Alarmingly, the warming and acidification of aquatic systems caused by climate change impair n-3 LCPUFA production, with an anticipated decrease of 80% by the year 2100. We tested whether n-3 LCPUFA consumption affects the physiology, morphology, behaviour and cognition of the chicks of a top marine predator, the ring-billed gull. Using a colony with little access to n-3 LCPUFAs, we supplemented siblings from 22 fenced nests with contrasting treatments from hatching until fledging; one sibling received n-3 LCPUFA-rich fish oil and the other, a control sucrose solution without n-3 LCPUFAs. Halfway through the nestling period, half the chicks receiving fish oil were switched to the sucrose solution to test whether n-3 LCPUFA intake remains crucial past the main growth phase (chronic versus transient treatments). Upon fledging, n-3 LCPUFAs were elevated in the blood and brains of chicks receiving the chronic treatment, but were comparable to control levels among those receiving the transient treatment. Across the entire sample, chicks with elevated n-3 LCPUFAs in their tissues fledged earlier despite their morphology and activity levels being unrelated to fledging age. Fledging required chicks to escape fences encircling their nest. We therefore interpret fledging age as a possible indicator of cognition, with chicks with improved cognition fledging earlier. These results provide insight into whether declining dietary n-3 LCPUFAs will compromise top predators' problem-solving skills, and thus their ability to survive in a rapidly changing world.

Maternal diet high in Omega-3 fatty acids upregulate genes involved in neurotrophin signalling in fetal brain during pregnancy in C57BL/6 mice.

Neurotrophins play a critical role in the development, maintenance, and proper function of the brain. We investigated the effects of maternal diet high in omega (n)-3 polyunsaturated fatty acids (PUFA) on fatty acids composition and the gene expression of neurotrophins in fetal brain at different gestation stages. Female C57BL/6 mice (7-weeks old, n = 8/group) were fed a diet containing high, low or very low n-3 PUFA (9, 3 or 1% w/w, respectively), with an n-6:n-3 PUFA of 5:1, 20:1 and 40:1, respectively, for two weeks before mating and throughout pregnancy. Animals were sacrificed during pregnancy at gestation day 12.5 and 18.5 to determine placental and fetal-brain fatty acids composition. The gene expressions of endothelial lipase (EL) and plasma membrane fatty acid-binding protein (FABPpm) were measured in the placenta, while major facilitator superfamily domain-containing 2a (Mfsd2a), brain-derived neurotrophic factor (BDNF), tropomyosin-receptor kinase (TrK)-B, and cAMP response element-binding protein (CREB) were measured in fetal-brain, using qPCR. The protein expression of phosphorylated CREB (pCREB) was determined using ELISA. The high n-3 PUFA diet increased the mRNA expression of EL, FABPpm, and Mfsd2a at both gestation days, compared to other groups. Docosahexaenoic acid (DHA) and total n-3 PUFA were significantly higher in the high n-3 PUFA group, compared to the other groups at both gestation days. The high n-3 PUFA diet also increased the mRNA expressions of BDNF, TrKB and CREB, as well as the protein concentration of pCREB as gestation progressed, compared to the other groups. Our findings show for the first time that maternal diet high in n-3 PUFA increased the mRNA expression of Mfsd2a, which correlated with an increase in DHA accretion in the fetal-brain. A diet high in n-3 PUFA increased neurotrophin signalling in fetal-brain as gestation progressed, demonstrating the importance of n-3 PUFA during brain development.

A high fat diet enriched with sea cucumber gut powder provides cardio-protective and anti-obesity effects in C57BL/6 mice.

We have previously reported that sea cucumber (SC) inhibits fat accumulation and insulin resistance in 3T3-L1 cells. The present study investigated the anti-obesity and cardio-protective effects of SC freeze-dried gut powder using C57BL/6 as an animal model. Male mice were fed a normal chow diet, a high fat diet (HFD) or a HFD enriched with 2.5, 5 or 7.5% SC gut powder for 4, 8 and 12weeks. Diets enriched with SC caused a significant reduction in body weight gain and fat weight, compared to the HFD, without affecting food intake. Both 2.5% and 5% SC treatment showed a significant reduction in plasma glucose, triacylglycerol (TG), total cholesterol (TC) and non-esterified fatty acids, compared to the HFD. However, animals fed the 7.5% SC diet showed an increase in liver weight, liver TG and TC, compared to the HFD diet. Diets enriched with 2.5% SC caused an increase in adiponectin mRNA expression in adipose tissue and reduced plasma interleukin-6, compared to the HFD diet. Fecal cholesterol excretion increased after 2.5% SC treatment, coinciding with an increase in ATP-binding cassette-5 and -8 mRNA expression in the small intestine. Although both 2.5 and 5% SC treatment caused weight and fat reduction to a similar extent, 2.5% SC was more effective at improving the metabolic profile. None of the tested SC doses caused any toxic effects. Our findings demonstrate for the first time that SC freeze-dried gut powder has the potential as a nutraceutical to target obesity and related disorders.

Arachidonic acid has a dominant effect to regulate lipogenic genes in 3T3-L1 adipocytes compared to omega-3 fatty acids.

BACKGROUND: The effects of long-chain n-3 and n-6 polyunsaturated fatty acids (PUFA) on the regulation of adipocytes metabolism are well known. These fatty acids are generally consumed together in our diets; however, the metabolic regulation of adipocytes in the presence of these fatty acids when given together is not known. OBJECTIVE: To investigate the effects of n-3 PUFA and arachidonic acid (AA), an n-6 PUFA, on the regulation of adipogenic and lipogenic genes in mature 3T3-L1 adipocytes. METHODS: 3T3-L1 adipocytes were incubated in the presence or absence of 100 µM of eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA; docosapentaenoic acid, DPA and AA, either alone or AA+n-3 PUFA; control cells received bovine serum albumin alone. The mRNA expression of adipogenic and lipogenic genes was measured. The fatty acid composition of adipocytes was analyzed using gas chromatography. RESULTS: Individual n-3 PUFA or AA had no effect on the mRNA expression of peroxisome-proliferator-activated receptor-γ; however, AA+EPA and AA+DPA significantly increased (P<0.05) the expression compared to control cells (38 and 42%, respectively). AA and AA+EPA increased the mRNA expression of acetyl-CoA carboxylase 1 (P<0.05). AA treatment decreased the mRNA expression of stearoyl-CoA desaturase (SCD1) (P<0.01), while n-3 PUFA, except EPA, had no effect compared to control cells. AA+DHA and AA+DPA inhibited SCD1 gene expression (P<0.05) suggesting a dominant effect of AA. Fatty acids analysis of adipocytes revealed a higher accretion of AA compared to n-3 PUFA. CONCLUSIONS: Our findings reveal that AA has a dominant effect on the regulation of lipogenic genes in adipocytes.

Anti-diabetic activity of swertiamarin is due to an active metabolite, gentianine, that upregulates PPAR-γ gene expression in 3T3-L1 cells.

We have previously shown the anti-diabetic effects of swertiamarin; however, pharmacokinetic analysis showed that swertiamarin had a plasma half-life of 1.3 h. Gentianine is an active metabolite of swertiamarin that possesses a pharmacophoric moiety. The aim of this study was to explore the possibility whether the anti-diabetic effect of swertiamarin is due to gentianine. Swertiamarin treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-γ and GLUT-4; however, there was a significant increase in the mRNA expression of adiponectin. On the other hand, treatment with gentianine significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-γ, GLUT-4 and adiponectin. These findings suggest, for the first time, that the anti-diabetic effect of swertiamarin is due to gentianine, an active metabolite of swertiamarin.

Bio F1B hamster: a unique animal model with reduced lipoprotein lipase activity to investigate nutrient mediated regulation of lipoprotein metabolism.

BACKGROUND: Bio F1B hamster is an inbred hybrid strain that is highly susceptible to diet-induced atherosclerosis. We previously reported that feeding a high fat fish oil diet to Bio F1B hamster caused severe hyperlipidaemia. In this study we compared the effects of various diets in the Bio F1B hamster and the Golden Syrian hamster, which is an outbred hamster strain to investigate whether genetic background plays an important role in dietary fat mediated regulation of lipoprotein metabolism. We further investigated the mechanisms behind diet-induced hyperlipidaemia in F1B hamster. METHODS: The Bio F1B and Golden Syrian hamsters, 8 weeks old, were fed high fat diets rich in either monounsaturated fatty acids, an n-6: n-3 ratio of 5 or a fish oil diet for 4 weeks. Animals were fasted overnight and blood and tissue samples were collected. Plasma was fractionated into various lipoprotein fractions and assayed for triacylglycerol and cholesterol concentrations. Plasma lipoprotein lipase activity was measured using radioisotope method. Microsomal triglyceride transfer protein activity was measured in the liver and intestine. Plasma apolipoproteinB48, -B100 and apolipoprotein E was measured using Western blots. Two-way ANOVA was used to determine the effect of diet type and animal strain. RESULTS: The fish oil fed F1B hamsters showed milky plasma after a 14-hour fast. Fish oil feeding caused accumulation of apolipoproteinB48 containing lipoprotein particles suggesting hindrance of triglyceride-rich lipoprotein clearance. There was no significant effect of diet or strain on hepatic or intestinal microsomal triglyceride transfer protein activity indicating that hyperlipidaemia is not due to an increase in the assembly or secretion of lipoprotein particles. F1B hamsters showed significantly reduced levels of lipoprotein lipase activity, which was inhibited by fish oil feeding. CONCLUSION: Evidence is presented for the first time that alterations in lipoprotein lipase activity and mRNA levels contribute to varied response of these hamsters to dietary fat, highlighting the importance of genetic background in the regulation of lipid and lipoprotein metabolism by dietary fats. Bio F1B hamster may prove to be an important animal model to investigate nutrient mediated regulation of metabolic parameters under lipoprotein lipase deficiency.

Differential regulation of cholesterol homeostasis in transgenic mice expressing human cholesterol ester transfer protein.

We investigated whether expression of cholesterol ester transfer protein (CETP) in mice alters the regulation of cholesterol metabolism. Transgenic mice expressing human CETP (CETP-TG) and nontransgenic littermates (non-TG) were fed either a monounsaturated fatty acid (MUFA) or a saturated fatty acid (SFA)-rich diet in the presence or absence of cholesterol. Mice fed with MUFA diet had higher CETP activity compared with SFA-fed mice. Addition of cholesterol to the MUFA diet decreased CETP activity, whereas addition of cholesterol to the SFA diet had no effect. Cholesterol 7alpha-hydroxylase (Cyp7a) activity was higher in CETP-TG mice compared with non-TG mice when fed a MUFA diet, whereas SFA fed CETP-TG mice showed lower Cyp7a activity as compared with non-TG. Microsomal triglyceride transfer protein (MTTP) activity was higher in CETP-TG mice compared with non-TG mice when fed a MUFA diet. HMG-CoA reductase activity was lower in CETP-TG mice compared with non-TG mice when fed a MUFA or a SFA diet. These data demonstrate that the regulation of Cyp7a, HMG-CoA reductase, and MTTP is altered in CETP-TG mice as compared with non-TG mice and these alterations are further modulated by the quality of dietary fats. These findings highlight the importance of CETP in regulating cholesterol homeostasis.

Maternal diet rich in saturated fats has deleterious effects on plasma lipids of mice.

BACKGROUND AND OBJECTIVES: High dietary fat intake has been reported to cause an alteration in lipid metabolism that is associated with an increased risk of cardiovascular disease. In the present study, an animal model was used to evaluate the effects of feeding diets rich in different fatty acids to mothers during pregnancy and lactation, and the effects of the maternal diet on parameters of lipid metabolism in adult offspring. The interaction between the offspring's own diet and the programming due to the maternal diet was also evaluated. METHODS: Female C57BL/6 mice were fed a high-fat diet (20% fat [weight to weight]) rich in either saturated fatty acids (SFA) or polyunsaturated fatty acids (PUFA) for two weeks before mating, during pregnancy and until weaning. The offspring were divided into two groups; each group was fed a high-fat diet enriched in either SFA or PUFA for eight weeks after weaning. The groups were designated as SFA/SFA (diet of the mother/diet of the offspring), SFA/PUFA, PUFA/PUFA and PUFA/SFA. Blood and tissues were collected at the end of the eight-week feeding period after an overnight fast. RESULTS: The plasma total cholesterol and low density lipoprotein cholesterol concentrations were significantly higher in the SFA/SFA group than in all other groups, whereas the PUFA/PUFA group had the lowest total cholesterol and low density lipoprotein cholesterol concentrations. Plasma high density lipoprotein cholesterol concentrations were significantly higher in the PUFA/SFA group than in the PUFA/PUFA and SFA/PUFA groups, whereas plasma triglyceride concentrations were not different among the groups. CONCLUSIONS: The data suggest that high maternal dietary fat intake during pregnancy affects lipid metabolism in the adult offspring. However, it appears that the offspring's own diet is also important in maintaining the regulation of lipid metabolism.

Lack of stimulation of cholesteryl ester transfer protein by cholesterol in the presence of a high-fat diet.

Cholesteryl ester transfer protein (CETP) is a key protein involved in the reverse cholesterol transport pathway. The regulation of CETP by dietary fats is not clearly understood. Transgenic mice expressing human CETP under the control of its natural flanking region were fed low- or high-fat diets enriched in monounsaturated fatty acids (MUFAs) or saturated fatty acids in the presence or absence of cholesterol. Addition of cholesterol to the low-fat MUFA diet increased CETP activity and mRNA expression, whereas addition of cholesterol to the high-fat MUFA diet led to a decrease in CETP activity and mRNA expression. In SW 872 cells, oleic acid and cholesterol stimulated CETP gene expression when given alone. However, addition of fatty acids along with cholesterol interfered with the stimulatory effect of cholesterol on CETP gene regulation. Cholesterol-mediated stimulation of CETP involves the transcription factor liver X receptor alpha (LXRalpha). High-fat MUFA diets inhibited the expression of LXRalpha, and addition of cholesterol to the high-fat MUFA diet did not rescue LXRalpha expression. Therefore, we present evidence for the first time that inhibition of LXRalpha expression by a high-fat MUFA diet leads to inhibition of CETP stimulation by cholesterol.

The levels of plasma low density lipoprotein are independent of cholesterol ester transfer protein in fish-oil fed F1B hamsters.

BACKGROUND: Cholesterol ester transfer protein (CETP) plays a major role in regulating the levels of LDL- and HDL-cholesterol. We previously observed a fish-oil-induced elevation of low-density lipoprotein (LDL)-and very-low-density lipoprotein (VLDL)-cholesterol concentrations and a decrease in high-density lipoprotein (HDL)-cholesterol concentration in F1B hamsters. The molecular mechanism/s by which fish oil induces hyperlipidaemic effect was investigated in this study. We examined whether the effects of dietary fish oil on plasma lipoprotein concentrations are due to fish-oil-induced alterations in plasma CETP activity. MIX diet, a diet supplemented with a mixture of lard and safflower oil, was used as the control diet. RESULTS: We found that fish oil feeding in hamsters reduced CETP mass as well as CETP activity. Increasing the dietary fat level of fish-oil from 5% to 20% (w/w) led to a further decrease in CETP mass. Supplementation with dietary cholesterol increased both CETP mass and CETP activity in fish-oil and MIX-diet fed hamsters. However, there was no correlation between CETP mass as well as CETP activity and LDL-cholesterol concentrations. CONCLUSION: These findings suggest that cholesterol ester transfer between HDL and LDL is not likely to play a major role in determining fish-oil-induced changes in LDL- and HDL-cholesterol concentrations in F1B hamsters. A possible role of reduced clearance of LDL-particles as well as dietary fat level and dietary cholesterol dependent changes in LDL-lipid composition have been discussed.

Hyperlipidaemic effect of fish oil in Bio F1B hamsters.

We investigated the dietary influence of low and high levels of fish oil, supplemented with or without dietary cholesterol, on the plasma lipoprotein profile in Bio F1B hamsters, a model susceptible to diet-induced hyperlipidaemia. The MIX diet, a diet supplemented with a mixture of lard and safflower-seed oil, was used as the control diet to maintain the saturated MUFA and PUFA levels similar to the fish-oil diet. The animals were fed the specific diets for 2 weeks and fasted for 14 h before killing. The plasma from the animals fed high levels of fish oil was milky and rich in chylomicron-like particles. The plasma total cholesterol, VLDL- and LDL-cholesterol and -triacylglycerol concentrations were significantly higher, whereas HDL-cholesterol was lower in hamsters fed fish oil compared with the MIX-diet-fed hamsters. Increasing the amount of fat in the diet increased plasma lipids in both the fish-oil- and the MIX-diet-fed hamsters; however, this hyperlipidaemic effect of dietary fat level was greater in the hamsters fed the fish-oil diet. The hepatic lipid concentrations were not dramatically different between the fish-oil-fed and the MIX-diet-fed hamsters. However, the hepatic LDL-receptor mRNA levels were significantly low in the fish-oil-fed hamsters compared with the MIX-diet-fed hamsters. Increasing the amount of fish oil in the diet further decreased the hepatic LDL-receptor mRNA expression. It is concluded that F1B hamsters are susceptible to fish-oil-induced hyperlipidaemia, especially at high fat levels, and this increase is partially explained by the inhibition of hepatic LDL-receptor mRNA expression.

Streptozotocin-induced increase in cholesterol ester transfer protein (CETP) and its reversal by insulin in transgenic mice expressing human CETP.

High plasma triacylglycerol and low high-density lipoprotein levels are risk factors for cardiovascular disease in diabetes. Plasma high-density lipoprotein levels are regulated by cholesterol ester transfer protein (CETP). The regulation of CETP under diabetic conditions is not clear, and this is due to a lack of appropriate models. We used transgenic mice expressing human CETP to study the regulation of this protein under type-1 diabetic conditions and further investigated whether insulin reverses the effect of diabetes. Mice expressing human CETP under the control of its natural flanking region and age-matched littermates not expressing this protein were made diabetic by injecting streptozotocin, and the reversal of diabetes was assessed by injecting insulin. The plasma total cholesterol, low-density lipoprotein-cholesterol, and triacylglycerol concentrations were elevated, whereas high-density lipoprotein-cholesterol concentrations were reduced after the onset of diabetes. Insulin injection partially recovered this effect. The plasma cholesterol ester transfer activity, CETP mass, and hepatic CETP mRNA abundance were significantly higher in diabetic mice that were partially restored by insulin administration. There was a strong correlation between high-density lipoprotein-cholesterol concentrations and cholesterol ester transfer activity. These results suggest that an increase in CETP under diabetic conditions might be a major factor responsible for increased incidence of diabetes-induced atherosclerosis.

Dietary rhubarb (Rheum rhaponticum) stalk fibre does not lower plasma cholesterol levels in diabetic rats.

Rhubarb (Rheum rhapontiam) stalk fibre was previously shown to be hypolipidaemic under clinical and experimental conditions. The present study was undertaken to investigate whether rhubarb stalk fibre has a hypolipidaemic effect under diabetic conditions. Two models of diabetic rats were used: streptozotocin-induced diabetic rats, and diabetes-prone BB (BBdp) rats. The plasma cholesterol and triacylglycerol concentrations were elevated after the onset of diabetes in BBdp rats, but not in sterptozotocin-induced diabetic rats. The rhubarb-fibre diet had no effect on the plasma cholesterol or triacylglycerol concentrations of diabetic rats. The hypolipidaemic effect of rhubarb stalk fibre has been suggested to be due to the bile-acid-binding capacity of rhubarb fibre, which in turn up regulates cholesterol 7alpha-hydroxylase (cyp7a) activity. cyp7a is the first and the rate-limiting enzyme in the breakdown of cholesterol to bile acids. We measured the cyp7a activity and mRNA levels in control and diabetic rats fed rhubarb- and cellulose-fibre diets. The cyp7a activity and mRNA abundance were increased in both diabetic rat models, indicating that bile acid synthesis is enhanced in diabetes. Feeding a diet enriched with rhubarb fibre caused a slight but significant increase (P<0.05) in cyp7a enzyme activity in BBdp rats, but no change in cyp7a mRNA abundance was detected. These results suggest that although a rhubarb-fibre-enriched diet increased cyp7a activity in BBdp rats, there was no apparent therapeutic benefit in terms of lowering plasma cholesterol concentrations.