Liver TAG Research Articles

Increasing intake of long-chainn-3 PUFA enhances lipoperoxidation and modulates hepatic gene expression in a dose-dependent manner

Long-chain (LC) n-3 PUFA have a broad range of biological properties that can be achieved at the gene expression level. This has been well described in liver, where LC n-3 PUFA modulate the expression of genes related to lipid metabolism. However, the complexity of biological pathway modulations and the nature of bioactive molecules are still under investigation. The present study aimed to investigate the dose-response effects of LC n-3 PUFA on the production of peroxidised metabolites, as potential bioactive molecules, and on global gene expression in liver. Hypercholesterolaemic rabbits received by daily oral administration (7 weeks) either oleic acid-rich oil or a mixture of oils providing 0.1, 0.5 or 1 % (groups 1, 2 and 3 respectively) of energy as DHA. Levels of specific peroxidised metabolites, namely 4-hydroxyhexenal (4-HHE)-protein adducts, issued from LC n-3 PUFA were measured by GC/MS/MS in liver in parallel to transcription profiling. The intake of LC n-3 PUFA increased, in a dose-dependent manner, the hepatic production of 4-HHE. At the highest dose, LC n-3 PUFA provoked an accumulation of TAG in liver, which can be directly linked to increased mRNA levels of lipoprotein hepatic receptors (LDL-receptor and VLDL-receptor). In groups 1 and 2, the mRNA levels of microsomal TAG transfer protein decreased, suggesting a possible new mechanism to reduce VLDL secretion. These modulations of genes related to lipoprotein metabolism were independent of PPARα signalling but were probably linked to the activation of the farnesol X receptor pathway by LC n-3 PUFA and/or their metabolites such as HHE.

Lipid metabolism of orchiectomised rats was affected by fructose ingestion and the amount of ingested fructose

We examined whether lipid metabolism in orchiectomised (ORX) rats was affected by fructose ingestion and the amount of ingested fructose. Sucrose was used as a fructose source. Sham-operated and ORX rats were fed one of the following three diets for 28 d: a maize starch-based diet without sucrose (SU0), a diet by which half or all of maize starch was replaced by sucrose (SU50 or SU100). Body-weight gain and food intake were increased by sucrose ingestion, but decreased by ORX. Plasma total cholesterol concentration was increased by ORX and dose-dependently by sucrose ingestion. Plasma TAG concentration was decreased by ORX, but was increased dose-dependently by sucrose ingestion. Plasma insulin concentration was decreased by ORX, but was not affected by sucrose ingestion. Liver TAG was increased by sucrose ingestion and ORX; however, liver cholesterol concentration was not affected by sucrose ingestion and ORX. The hepatic activity of cholesterol 7α-hydroxylase 1 was not affected by sucrose ingestion and ORX; however, faecal excretion of bile acids was decreased. The mRNA level of microsomal TAG transfer protein, which is the gene related to hepatic VLDL production, was increased by ORX and sucrose ingestion. The mRNA level of uncoupling protein-1 was decreased by ORX, but not by sucrose ingestion. Plasma insulin concentration tended to correlate with the level of sterol-regulatory element-binding protein-1c mRNA (r 0·747, P = 0·088). These results show that lipid metabolism in ORX rats would be affected by the consumption of fructose-rich sweeteners such as sucrose and high-fructose syrup.

Rat liver mitochondrial membrane characteristics and mitochondrial functions are more profoundly altered by dietary lipid quantity than by dietary lipid quality: effect of different nutritional lipid patterns

Dietary lipids are known to affect the composition of the biological membrane and functions that are involved in cell death and survival. The mitochondrial respiratory chain enzymes are membrane protein complexes whose function depends on the composition and fluidity of the mitochondrial membrane lipid. The present study aimed at investigating the impact of different nutritional patterns of dietary lipids on liver mitochondrial functions. A total of forty-eight Wistar male rats were divided into six groups and fed for 12 weeks with a basal diet, lard diet or fish oil diet, containing either 50 or 300g lipid/kg. The 30% lipid intake increased liver NEFA, TAG and cholesterol levels, increased mitochondrial NEFA and TAG, and decreased phospholipid (PL) levels. SFA, PUFA and unsaturation index (UI) increased, whereas MUFA and trans-fatty acids (FA) decreased in the mitochondrial membrane PL in 30% fat diet-fed rats compared with 5% lipid diet-fed rats. PL UI increased with fish oil diet v. basal and lard-rich diets, and PL trans-FA increased with lard diet v. basal and fish oil diets. The 30% lipid diet intake increased mitochondrial membrane potential, membrane fluidity, mitochondrial respiration and complex V activity, and decreased complex III and IV activities. With regard to lipid quality effects, β-oxidation decreased with the intake of basal or fish oil diets compared with that of the lard diet. The intake of a fish oil diet decreased complex III and IV activities compared with both the basal and lard diets. In conclusion, the characteristics and mitochondrial functions of the rat liver mitochondrial membrane are more profoundly altered by the quantity of dietary lipid than by its quality, which may have profound impacts on the pathogenesis and development of non-alcoholic fatty liver disease.

Resveratrol attenuates steatosis in obese Zucker rats by decreasing fatty acid availability and reducing oxidative stress

Non-alcoholic fatty liver disease (NAFLD) is one of the most common manifestations of chronic liver disease worldwide. The aim of the present study was to assess the effect of resveratrol on liver fat accumulation, as well as on the activity of those enzymes involved in lipogenesis and fatty acid oxidation in fa/fa Zucker rats. A total of thirty rats were assigned to three experimental groups and orally treated with resveratrol for 6 weeks, or without resveratrol (C: control group; RSV15 group: 15mg/kg body weight per d; RSV45 group: 45mg/kg body weight per d). Liver histological analysis was performed by microscopy. Levels of hepatic carnitine palmitoyltransferase-Ia (CPT-Ia), acyl-coenzyme A oxidase (ACO), fatty acid synthase, glucose-6-phosphate dehydrogenase and malic enzyme were assessed by spectrophotometry, and acetyl-CoA carboxylase was assessed by radiometry. Commercial kits were used to determine serum TAG, NEFA, total HDL and non-HDL-cholesterol, glycerol, ketonic bodies, glucose, insulin, adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), hepatic TAG, thiobarbituric acid reactive substrates, GSH (GSSG) and superoxide dismutase. Resveratrol reduced liver weight and TAG content. It did not modify the activity of lipogenic enzymes but it did increase CPT-Ia and ACO activities. NEFA and ALP were reduced in both resveratrol-treated groups. AST/GOT was reduced only by the lowest dose. ALT/GPT, TAG and adiponectin remained unchanged. Resveratrol reduced liver oxidative stress. This study demonstrates that resveratrol can protect the liver from NAFLD by reducing fatty acid availability. Moreover, resveratrol also protects liver from oxidative stress.

Fish oil combined with SCFA synergistically prevent tissue accumulation of NEFA during weight loss in obese mice

Based on their proposed metabolic effects, we examined whether fish oil (FO) and SCFA, alone or in combination, accelerate weight loss and the resultant metabolic improvements. Obesity was induced in male C57BL/6J mice by high-energy feeding for 10 weeks. The mice were transferred to a low-fat diet (2·5w%) for 4 weeks, the source of fat being either FO, a lard-safflower oil mix (control), or both types combined with SCFA. Weight, fasting insulin, tissue and serum lipid concentrations, as well as mRNA amount of genes related to adipose inflammation and hepatic fat oxidation were determined. All groups lost weight and showed reduced fasting insulin concentrations and reduced liver TAG. However, weight loss on the control-fat diet caused significant increase in hepatic and cardiac NEFA. Substituting 20% of the fat with SCFA increased weight loss by 48% and reduced fasting insulin 1·5-fold more than the no-SCFA diets. It furthermore significantly increased the amount of mRNA for PPAR-α, and decreased the mRNA amount for NF-κB in the liver and white adipose tissue. The FO diets enhanced improvement of tissue lipid levels. Thus, FO improved liver TAG and NEFA levels compared with weight loss on the control diet. Combining FO and SCFA further reduced tissue NEFA accumulation. In conclusion, we found that dietary SCFA had a significant impact on gene expression in the liver and adipose tissue, and that the effect of FO on tissue NEFA content was modified by SCFA. Thus, interactions between fatty acids should be considered when studying the effects of specific fatty acids.

Dietary plant proteins and vegetable oil blends increase adiposity and plasma lipids in Atlantic salmon (Salmo salarL.)

In order to study whether lipid metabolism may be affected by maximum replacement of dietary fish oil and fish meal with vegetable oils (VO) and plant proteins (PP), Atlantic salmon (Salmo salar L.) smolts were fed a control diet containing fish oil and fish meal or one of three plant-based diets through the seawater production phase for 12 months. Diets were formulated to meet all known nutrient requirements. The whole-body lipid storage pattern was measured after 12 months, as well as post-absorptive plasma, VLDL and liver TAG. To further understand the effects on lipid metabolism, expression of genes encoding for proteins involved in VLDL assembly (apoB100), fatty acid uptake (FATP1, cd36, LPL and FABP3, FABP10 and FABP11) were measured in liver and visceral adipose tissue. Maximum dietary VO and PP increased visceral lipid stores, liver TAG, and plasma VLDL and TAG concentrations. Increased plasma TAG correlated with an increased expression of apoB100, indicating increased VLDL assembly in the liver of fish fed the high-plant protein- and VO-based diet. Atlantic salmon fed intermediate replacement levels of VO or PP did not have increased body fat or visceral mass. Overall, the present results demonstrate an interaction between dietary lipids and protein on lipid metabolism, increasing overall adiposity and TAG in the body when fish meal and fish oil are replaced concomitantly at maximised levels of VO and PP.

A polyphenol extract modifies quantity but not quality of liver fatty acid content in high-fat–high-sucrose diet-fed rats: possible implication of the sirtuin pathway

High-fat or high-fat-high-sucrose diets are known to induce non-alcoholic fatty liver disease and this is emerging as one of the most common liver diseases worldwide. Some polyphenols have been reported to decrease rat hepatic lipid accumulation, in particular those extracted from red grapes such as resveratrol. The present study was designed to determine whether a polyphenol extract (PPE), from red grapes, modulates liver fatty acid composition and desaturase activity indexes in rats fed a high-fat-high-sucrose (HFHS) diet, and to explore whether sirtuin-1 deacetylase activation was implicated in the effect of the PPE against liver steatosis. The effect of this PPE on mitochondriogenesis and mitochondrial activity was also explored. The PPE decreased liver TAG content in HFHS+PPE diet-fed rats in comparison with HFHS diet-fed rats. The PPE had no effect on liver fatty acid composition, desaturase activity indexes and stearoyl-CoA desaturase 1 (SCD1) gene expression. Sirtuin-1 deacetylase protein expression was significantly increased with the PPE; AMP kinase protein expression was higher with the PPE in comparison with the HFHS rats, but no modification of phosphorylated AMP kinase was observed. Protein expression of phospho-acetyl-CoA carboxylase was decreased in HFHS rats and returned to basal values with the PPE. Finally, the PPE modulated PPARγ coactivator-1α (PGC-1α) but did not modify mitochondriogenesis and mitochondrial activity. In conclusion, the PPE partially prevented the accumulation of TAG in the liver by regulating acetyl-CoA carboxylase phosphorylation, a key enzyme in lipid metabolism, probably via sirtuin-1 deacetylase activation. However, the PPE had no effect on the qualitative composition of liver fatty acids.

The hypocholesterolaemic effects ofLactobacillus acidophilusAmerican Type Culture Collection 4356 in rats are mediated by the down-regulation of Niemann-Pick C1-Like 1

The objective of the present study was to evaluate the effect of Lactobacillus acidophilus 4356 on cholesterol metabolism in vivo. Rats were fed a cholesterol-enriched experimental diet with or without L. acidophilus 4356 supplementation at a dose of 10(9) colony-forming units per d. L. acidophilus 4356 feeding significantly lowered total serum cholesterol, LDL-cholesterol and TAG concentrations, but there was no change in the serum HDL-cholesterol concentrations. In addition, total liver cholesterol and TAG were decreased in the L. acidophilus 4356-fed group. The expression of Niemann-Pick C1-Like 1 (NPC1L1) in the duodenum and jejunum was significantly decreased following L. acidophilus 4356 feeding. Lactobacillus acidophilus 4356 increased the population of lactobacilli and bifidobacteria in the small intestine and faeces compared with the control. These results indicate that the probiotic potential of the L. acidophilus 4356 strain in the control of cholesterol is at least partially mediated by the down-regulation of NPC1L1. Furthermore, these results also potentially suggest a new mechanism that is responsible for the cholesterol-reducing effects of probiotics.

Effect of phospholipid n‐3 polyunsaturated fatty acids on rat lipid metabolism

AbstractIt has been demonstrated that the amount and type of dietary fat are factors involved in the risk of arteriosclerosis and coronary or cerebral artery disease through lipid metabolism. In this study, we investigated the effects of phospholipids (PLs) containing n‐3PUFAs on lipid metabolism in rats. PLs containing n‐3PUFAs were prepared from squid (Todarodes pacificus) mantle muscle. Groups of male Wistar rats were fed AIN93G diet containing soybean oil (SO, 7%), fish oil (1.2%) + SO (5.8%), soybean PLs (1.8%) + SO (5.2%), or PLs containing n‐3PUFAs (1.8%) + SO (5.2%). The following indicators were assayed as indexes of lipid metabolism: TAG and cholesterol in serum and liver, fecal cholesterol, bile‐acid excretion, and liver mRNA expression levels of genes encoding proteins involved in cholesterol homeostasis. Serum and liver TAG contents decreased significantly in the group fed PLs containing n‐3PUFAs as compared to other groups, accompanied by a significant decline in the expression level of sterol regulatory element binding protein‐1c. The decrease in cholesterol content in the group fed PLs containing n‐3PUFAs was due to the increase in fecal cholesterol excretion and the increase of mRNA expression levels of ATP‐binding cassette (ABC) G5 and ABCG8 in liver.Practical applications: PLs containing n‐3PUFAs decreased serum and liver TAG contents compared with that induced by soybean PLs. Further, PLs containing n‐3PUFAs can induce a reduction in serum and liver cholesterol concentrations as well as the triglyceride‐reducing effect of conventional n‐3PUFAs containing TAG. In other words, dietary n‐3PUFAs contained in PLs can prevent life‐style diseases such as hyperlipidemia, arteriosclerosis and coronary, or cerebral artery disease more effectively than TAG containing n‐3PUFAs. Therefore, it is expected that the risk of lifestyle diseases would be decreased if PL containing n‐3PUFAs can be supplied routinely. In this study, PLs containing n‐3PUFAs were prepared from squid mantle muscle. On an industrial scale, such PLs can be produced from various unused resources and waste materials of fisheries. We conclude that highly functional foods could be developed based on the findings of this study, and would be available for health promotion worldwide.

Betaine supplementation affects the cholesterol but not the lipid profile of pigs

AbstractThis study was undertaken to investigate the effects of long term betaine intake on the cholesterol and lipid profile of Alentejano (AL) pigs. At ˜36 kg body weight (BW), castrated male and female pigs fed a commercial (C) diet, were divided into two groups: i) Group C, consuming the C diet; and ii) Group CB, consuming the C diet supplemented with 1 g/kg betaine. Pigs were slaughtered at ˜100 kg BW. Fasting plasma concentrations of protein, urea, glucose, TAG, phospholipids, homocysteine, total and LDL‐ and HDL‐cholesterol were determined. Liver TAG, phospholipids, and total and free cholesterol were analyzed, as well as total lipids, cholesterol contents, and fatty acid (FA) composition of M. semimembranosus and dorsal subcutaneous fat. Betaine supplemented pigs presented significantly higher plasma concentrations of TAG, phospholipids, cholesterol, and lipoprotein cholesterol. Dorsal subcutaneous fat cholesterol concentration was also significantly higher in CB than in C pigs. No differences were detected in the most abundant FA profile (including the unsaturated to saturated FA ratio) of muscle and subcutaneous fat tissues among treatments. These data suggest that betaine induces dyslipidemia, and increases cholesterol concentration in dorsal subcutaneous fat, without affecting the FA profile of M. semimembranosus and dorsal subcutaneous fat.

Inflammation and adipose tissue: effects of progressive load training in rats

IntroductionCytokines (IL-6, IL-10 and TNF-α) are increased after exhaustive exercise in the rat retroperitoneal (RPAT) and mesenteric adipose tissue (MEAT) pads. On the other hand, these cytokines show decreased expression in these depots in response to a chronic exercise protocol. However, the effect of exercise with overload combined with a short recovery period on pro- and anti-inflammatory cytokine expression is unknown. In the present study, we investigated the regulation of cytokine production in the adipose tissue of rats after an overtraining-inducing exercise protocol.MethodsMale Wistar rats were divided into four groups: Control (C), Trained (Tr), Overtrained (OT) and recovered overtrained (R). Cytokines (IL-6, TNF-α and IL-10) levels and Toll Like Receptor 4 (TLR4), Nuclear Factor kBp65 (NF-kBp65), Hormone Sensitive Lipase (HSL) and, Perilipin protein expression were assessed in the adipose tissue. Furthermore, we analysed plasma lipid profile, insulin, testosterone, corticosterone and endotoxin levels, and liver triacylglycerol, cytokine content, as well as apolipoprotein B (apoB) and TLR4 expression in the liver.ResultsOT and R groups exhibited reduced performance accompanied by lower testosterone and increased corticosterone and endotoxin levels when compared with the control and trained groups. IL-6 and IL-10 protein levels were increased in the adipose tissue of the group allowed to recover, in comparison with all the other studied groups. TLR-4 and NF-kBp65 were increased in this same group when compared with both control and trained groups. The protein expression of HSL was increased and that of Perilipin, decreased in the adipose in R in relation to the control. In addition, we found increased liver and serum TAG, along with reduced apoB protein expression and IL-6 and IL-10 levels in the of R in relation to the control and trained groups.ConclusionIn conclusion, we have shown that increases in pro-inflammatory cytokines in the adipose tissue after an overtraining protocol may be mediated via TLR-4 and NF-kBp65 signalling, leading to an inflammatory state in this tissue.

Effect of prebiotic fibre supplementation on hepatic gene expression and serum lipids: a dose–response study in JCR:LA-cp rats

Prebiotic fibres have been proposed to promote weight loss and lower serum cholesterol; however, the mechanisms are not fully understood. The aim of the present research was to identify possible mechanisms through which prebiotic fibres improve serum lipids. Lean and obese JCR:La-cp rats aged 8 weeks consumed one of three diets supplemented with 0, 10 or 20 % prebiotic fibre for 10 weeks. Rats were anaesthetised and a fasting blood sample was taken for lipid analysis. Real-time PCR was used to determine gene expression for cholesterol and fatty acid regulatory genes in liver tissue. Liver and caecal digesta cholesterol and TAG content were quantified. Both doses of prebiotic fibre lowered serum cholesterol levels by 24 % in the obese hyperlipidaemic rats (P < 0.05). This change was associated with an increase in caecal digesta as well as an up-regulation of genes involved in cholesterol synthesis and bile production. Additionally, there was a 42 % reduction in TAG accumulation in the liver of the obese rats with 10 % prebiotic diet (P < 0.05); however, no change in liver fatty acid synthase (FAS). Prebiotic fibres appear to lower cholesterol levels through increased cholesterol excretion in the form of bile and inhibit the accumulation of TAG in the liver through a mechanism unrelated to FAS. These effects appear to be limited to the obese model and particularly the 10 % dose. The present work is significant as it provides insight into the mechanisms of action for prebiotic fibres on lipid metabolism and furthers the development of dietary treatments for hypercholesterolaemia.

Oral supplementation of propionyl-l-carnitine reduces body weight and hyperinsulinaemia in obese Zucker rats

Propionyl-L-carnitine (PLC) is an SCFA esterified to carnitine that plays an important role in fatty acid oxidation and energy expenditure, in addition to having a protective effect on the endothelium. In order to evaluate the effect of PLC on an animal model of obesity, insulin resistance and, consequently, endothelial dysfunction, lean and obese Zucker rats (OZR) received either vehicle- or PLC-supplemented drinking water (200 mg/kg per d) for 20 weeks. Body weight, food intake, systolic blood pressure and heart rate were controlled weekly and an oral glucose tolerance test was performed. Fasting glucose, TAG, cholesterol, HDL, NEFA, adiponectin and insulin were analysed in serum. Visceral adipose tissue and liver were weighed and liver TAG liver composition was evaluated. Endothelial and vascular functions were assessed in the aorta and small mesenteric arteries by response to acetylcholine, sodium nitroprusside and phenylephrine (Phe); NO participation was evaluated after incubation with the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and endothelial NOS protein expression by Western blotting. PLC decreased body-weight gain, food intake, adiposity, insulin serum concentration and TAG liver content and improved insulin resistance. Aortae from OZR receiving either vehicle or PLC exhibited a lower contractile response to Phe. PLC-treated OZR showed an enhanced release of endothelial NO upon the adrenergic stimulation. The protection of vascular function found after treatment with PLC in an animal model of insulin resistance supports the necessity of clinical trials showing the effect of L-carnitine supplements on metabolic disorders.

Trans-10,cis-12-conjugated linoleic acid reduces the hepatic triacylglycerol content and the leptin mRNA level in adipose tissue in obese Zucker fa/fa rats

Conjugated linoleic acid (CLA) isomers have been reported to reduce body weight and beneficially affect glucose metabolism in animals, but the results are inconsistent and seem to depend on animal model and type of CLA isomer. In the present study, feeding male Zucker fa/fa rats diets supplemented with 1% trans-10, cis-12-CLA for 10 d reduced the liver TAG content without improving the overall adiposity, and enhanced hepatic mitochondrial and peroxisomal beta-oxidation. The increased carnitine palmitoyltransferase (CPT)-I activity and mRNA level as well as the increased n-3:n-6 PUFA ratio in liver suggest that trans-10, cis-12-CLA increased the hepatic beta-oxidation by stimulation of PPARalpha. The reduced hepatic TAG content may be partly due to lower activity of stearoyl-CoA desaturase, as the ratios of 18 : 1n-9:18 : 0 and 16 : 1n-7:16 : 0 were reduced in liver. Trans-10, cis-12-CLA increased the CPT-I mRNA in retroperitoneal white adipose tissue (WAT), and increased uncoupling protein-2 mRNA in epididymal and inguinal WAT depots. Leptin mRNA level was decreased in all examined WAT depots, implying reduced insulin sensitivity. The resistin mRNA level was increased in all WAT depots, whereas adiponectin mRNA was reduced in inguinal and retroperitoneal WAT. The present results suggest that dietary supplementation with trans-10, cis-12-CLA may increase the catabolism of lipids in liver and adipose tissue. Moreover, we provide new data suggesting that trans-10, cis-12-CLA modulates the expression of resistin and adiponectin inversely in adipose tissue. Hence, the present results suggest that trans-10, cis-12-CLA may have some beneficial effects on lipid metabolism and adiposity but possibly reduces insulin sensitivity.

Effect of dietary conjugated linoleic acid isomers on lipid metabolism in hamsters fed high-carbohydrate and high-fat diets

Dietary conjugated linoleic acids (CLA) have been reported to have a number of isomer-dependent effects on lipid metabolism including reduction in adipose tissue deposition, changes in plasma lipoprotein concentrations and hepatic lipid accumulation. The aim of this study was to compare the effect of individual CLA isomers against lipogenic and high 'Western' fat background diets. Golden Syrian hamsters were fed a high-carbohydrate rodent chow or chow supplemented with 17.25 % fat formulated to represent the type and amount of fatty acids found in a typical 'Western' diet (including 0.2 % cholesterol). Diets were further supplemented with 0.25 % (w/w) rapeseed oil, cis9, trans11 (c9,t11)-CLA or trans10, cis12 (t10,c12)-CLA. Neither isomer had a significant impact on plasma lipid or lipoprotein concentrations. The t10,c12-CLA isomer significantly reduced perirenal adipose tissue depot mass. While adipose tissue acetyl CoA carboxylase and fatty acid synthase mRNA concentrations (as measured by quantitative PCR) were unaffected by CLA, lipoprotein lipase mRNA was specifically reduced by t10,c12-CLA, on both background diets (P < 0.001). This was associated with a specific reduction of sterol regulatory element binding protein 1c expression in perirenal adipose tissue (P = 0.018). The isomers appear to have divergent effects on liver TAG content with c9,t11-CLA producing lower concentrations than t10,c12-CLA. We conclude that t10,c12-CLA modestly reduces adipose tissue deposition in the Golden Syrian hamster independently of background diet and this may possibly result from reduced uptake of lipoprotein fatty acids, as a consequence of reduced lipoprotein lipase gene expression.

Liver TAG Transiently Decreases While PL n‐3 and n‐6 Fatty Acids are Persistently Elevated in Insulin Resistant Mice

Changes in fatty acid metabolism associated with insulin resistance have been described in rats and humans but have not been well characterized in the frequently used mouse model of diet-induced obesity. To analyse the early phase as well as established insulin resistance, C57BL/6 mice were placed for 1 or 16 weeks on a high fat diet (1w-HFD, 16w-HFD). Endocrine and metabolic parameters indicated that 1w-HFD mice showed a moderate but significant induction of insulin resistance while 16w-HFD mice exhibited profound obesity-associated insulin resistance and dyslipidemias. Significant alterations in fatty acid composition were observed in plasma and liver in both groups. Liver phospholipid-associated arachidonate and docosahexaenoate were increased in both 1w-HFD and 16w-HFD mice, possibly due to increased expression of the desaturases Fads1 and Fads2. Unexpectedly, SCD1 activity and gene expression in liver were decreased in the 1w-HFD group accompanied by diminished total hepatic lipid levels, while they were increased in chronically fed mice. Our data indicate that the early phase of HFD-induced insulin resistance is not associated with elevated liver lipid concentration. Furthermore, the early and persistent rise of arachidonate and docosahexaenoate indicates that insulin resistance is not due to insufficient availability (or concentrations) of polyunsaturated fatty acids as postulated previously.

Long-term consumption of saponins derived from Platycodi radix (22 years old) enhances hepatic insulin sensitivity and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed a high-fat diet

Crude saponins derived from Chinese Platycodi radix have been reported to prevent increases in body weight and liver TAG in mice fed a high-fat diet. We investigated the effects of an extract (PR) taken from Korean Platycodi radix, which is cultivated for 22 years in the ground (Jangsaeng doraji), and its saponins (PRS) on insulin resistance and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed high-fat diets. Four groups were orally supplemented with 2 g PR, 0.2 g PRS, 20 mg rosiglitazone (positive control) or 0.5 g cellulose (negative control) per kg body weight on a daily basis for 8 weeks. We found that PRS lowered body weight, visceral fat mass and serum leptin levels in pancreatectomized rats in comparison to the control. PR enhanced first- and second-phase insulin secretion while PRS stimulated only first-phase insulin secretion. Glucose infusion rates to maintain euglycaemia at hyperinsulinaemic states decreased in a descending order of rosiglitazone, PRS, PR and control, but they increased hepatic glucose output in the same order. This reduction was associated with the storage of decreased TAG and increased glycogen, which was a result of enhanced tyrosine phosphorylation of anti-insulin receptor substrate-2 and serine473 phosphporylation of protein kinase B (PKB, Akt). Improved hepatic insulin signalling led to decreased phosphoenolpyruvate carboxykinase expression and reduced hepatic glucose output accordingly. In conclusion, PRS principally improves glucose homeostasis by enhancing hepatic insulin sensitivity as a consequence of reducing fat storage and stimulating insulin signalling in diabetic rats. In addition, PR contains components that promote glucose-stimulated insulin secretion.

Hypolipidaemic effect of maize starch with different amylose content in ovariectomized rats depends on intake amount of resistant starch

The effect of amylose content on digestibility of starch in the small intestine and on the concentration of plasma lipid were studied in ileorectostomized rats and in ovariectomized rats, respectively. Seven kinds of starch with different amylose content (0, 27, 54, 62, 76, 79, 86 %) were used as test starch, which contained 0.4, 5.6, 37.1, 40.2, 45.6, 36.9 and 36.1 % resistant starch (RS), respectively. Rats were fed one of test diets containing 30 % test starch with different amylose content for 14 d in ileorectostomized and for 21 d in ovariectomized rats. Food intake was not significantly different among the groups. In ileorectostomized rats, the small intestinal starch digestibility decreased with increasing intakes of amylose and RS. In ovariectomized rats, body weight gain was lower on the higher amylose maize starch diets. The concentrations of plasma TAG and cholesterol decreased with increasing intake of RS. The concentrations of liver total lipids and TAG decreased with increasing intake of RS, but that of liver cholesterol did not. There was significant positive correlation between the level of sterol regulatory element-binding protein-1c mRNA and concentration of liver TAG. Total SCFA amount in the caecum increased logarithmically with increasing dry weight of caecal contents. The amount of bile acids in the small intestinal content and the excretions of bile acids and neutral steroids in faeces increased with increasing RS intake. These results show that starch rich in RS is more effective in preventing ovarian hormone deficiency-induced hyperlipidaemia.

Lupin protein influences the expression of hepatic genes involved in fatty acid synthesis and triacylglycerol hydrolysis of adult rats

To assess the effect of lupin protein on concentrations of lipids in plasma lipoproteins and liver and hepatic mRNA concentrations of genes involved in lipid metabolism, adult rats were fed egg albumin-based diets containing either lupin protein from Lupinus albus or casein (50 g/kg) supplemented (hypercholesterolaemic) or not (normolipaemic) with a cholesterol-cholate mixture for 20 d. Lupin protein compared with casein lowered the concentrations of TAG in liver (P < 0.01) and circulating VLDL + chylomicrons (P < 0.05) of hypercholesterolaemic rats, but not of normolipaemic rats. Hepatic mRNA concentrations of genes involved in fatty acid synthesis such as sterol regulatory element-binding protein-1c, glucose-6-phosphate dehydrogenase, fatty acid synthase, stearoyl-CoA desaturase-1 and acyl-CoA:glycerol-3-phosphate acyltransferase were lower and mRNA concentrations of lipoprotein lipase, hepatic lipase and apoA5 involved in TAG hydrolysis were higher in rats fed lupin protein than in rats fed casein. These effects were stronger in hypercholesterolaemic rats than in normolipaemic rats. Hypercholesterolaemic rats fed the lupin protein had higher liver cholesterol concentrations (P < 0.01) and lower levels of LDL-cholesterol (P < 0.05) than rats fed casein. No effect of lupin protein was observed on cholesterol concentration in VLDL + chylomicrons and HDL and hepatic mRNA concentrations of genes involved in cholesterol and bile acid metabolism. In conclusion, the present study shows that lupin protein has hypotriacylglycerolaemic action possibly via down regulation of fatty acid synthesis genes and up regulation of genes involved in TAG hydrolysis. Alterations in cholesterol metabolism could not be explained on the basis of mRNA data.

Effects of milk fermented byLactobacillusgasseriSBT2055 on adipocyte size in rats

Despite adequate scientific evidence of the potential benefits of probiotics to human health or disease prevention, their contribution to the growth of adipose tissue remains to be established. Four-week-old male Sprague-Dawley rats were fed a diet containing skim milk (control diet) or skim milk fermented by Lactobacillus gasseri SBT2055 (LGSP diet) for 4 weeks. Their body weight gain, adipose tissue weight, adipocyte size distribution profile, blood and hepatic lipids, and serum leptin, glucose and adiponectin levels were determined. There was a significant reduction in average adipocyte size in mesenteric white adipose tissue (P = 0.004). Moreover, the rats fed the LGSP diet displayed greater numbers of small adipocytes from mesenteric and retroperitoneal adipose tissues than did those on the control diet. Whereas adiponectin concentrations did not differ between the groups, serum leptin concentrations were decreased to 32 % in the LGSP diet group compared with the control group. Concentrations of serum glucose and lipids, and liver lipids, except for the liver TAG level, were similar in the two groups. These results indicate a possible role for a fermented milk product in the regulation of adipose tissue growth.