Effects of high-fat diet and physical activity on pyruvate dehydrogenase kinase-4 in mouse skeletal muscle

Background

The expression of PDK4 is elevated by diabetes, fasting and other conditions associated with the switch from the utilization of glucose to fatty acids as an energy source. It is previously shown that peroxisome proliferator-activated receptor ?? coactivator 1?? (PGC-1??), a master regulator of energy metabolism, coactivates in cell lines pyruvate dehydrogenase kinase-4 (PDK4) gene expression via the estrogen-related receptor ?? (ERR??). We investigated the effects of long-term high-fat diet and physical activity on the expression of PDK4, PGC-1?? and ERR?? and the amount and function of mitochondria in skeletal muscle.

Methods

Insulin resistance was induced by a high-fat (HF) diet for 19?weeks in C57BL/6?J mice, which were either sedentary or with access to running wheels. The skeletal muscle expression levels of PDK4, PGC-1?? and ERR?? were measured and the quality and quantity of mitochondrial function was assessed.

Results

The HF mice were more insulin-resistant than the low-fat (LF) -fed mice. Upregulation of PDK4 and ERR?? mRNA and protein levels were seen after the HF diet, and when combined with running even more profound effects on the mRNA expression levels were observed. Chronic HF feeding and voluntary running did not have significant effects on PGC-1?? mRNA or protein levels. No remarkable difference was found in the amount or function of mitochondria.

Conclusions

Our results support the view that insulin resistance is not mediated by the decreased qualitative or quantitative properties of mitochondria. Instead, the role of PDK4 should be contemplated as a possible contributor to high-fat diet-induced insulin resistance.     

Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring

Purpose

Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch.

Methods

Female MF-1 mice were fed a normal protein (NP, 18 % casein) or a protein-restricted (PR, 9 % casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45 % kcal fat) or standard chow (C, 7 % kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups (n = 7–11 per group).

Results

PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring (P < 0.01), but not in PR/HF offspring, compared with their chow-fed counterparts. However, the PR/HF offspring exhibited greater adiposity (P < 0.01) v the NP/HF group. The NP/HF offspring had increased energy expenditure and increased mRNA expression of uncoupling protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P < 0.01). No such differences in energy expenditure and iBAT gene expression were observed between the PR/HF and PR/C offspring.

Conclusions

These data suggest that a mismatch between maternal diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood.     

Maternal high-fat diet is associated with altered pancreatic remodelling in mice offspring

Purpose

To investigate whether a maternal high-fat diet (HF) during pregnancy and/or suckling periods predisposes adult C57BL/6 mice offspring to morphological pancreatic modifications.

Methods

Male pups were divided into 5 groups: SC (standard chow)—from dams fed SC during gestation and lactation, maintaining an SC diet from postweaning to adulthood; G—from dams fed HF diets during gestation; L—from dams fed HF diets during lactation; GL—from dams fed HF diets during gestation and lactation; and GL/HF—from dams fed HF diets during gestation and lactation, maintaining an HF diet from postweaning to adulthood. We analysed body mass (BM), plasma insulin, pancreas and adipose tissue structures.

Results

During the entire experiment, the SC group had the lowest BM. However, GL/HF offspring were heavier than the other groups. This weight gain was also accompanied by adipocyte hypertrophy. At 3 months, G offspring showed an increased insulin levels and impairment in carbohydrates metabolism. Furthermore, pancreatic islets were hypertrophied in G, GL and GL/HF offspring in comparison with SC offspring.

Conclusion

HF diet administration during the gestation period is more harmful than during the lactation period, exerting deleterious effects on pancreatic morphology in addition to larger fat deposits in adult mice offspring.     

Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance

Purpose

Obesity increases the risk of diabetes. The dysregulation of estrogen metabolism has been associated with the susceptibility to obesity and diabetes. Here, we explore the role estrogen plays in sex differences in obesity and glucose metabolism, specifically adipocyte biology.

Methods

We randomized C57BL/6?J male, non-ovariectomized female, ovariectomized female, and ovariectomized female mice supplemented with 17β estradiol to receive a calorie-restricted, low- or a high-fat diet (15 mice per group). We measured weight gained, calories consumed, percent body fat, abdominal adipose tissue, adipocyte size, lipogenic and adipogenic gene expression, and glucose tolerance.

Results

Male mice had a higher susceptibility to obesity than intact female mice. However, removal of the ovaries in female mice eliminated the protection to obesity and estrogen supplementation restored this protection. Male and ovariectomized female mice gained weight predominately in the form of abdominal adipose tissue possibly due to an increase in adipocyte size. Moreover, for mice consuming the high-fat diet, male and ovariectomized female mice had significantly higher levels of leptin mRNA and lower hormone-sensitive lipase mRNA relative to intact female mice and ovariectomized female mice supplemented with estrogen. Additionally, estrogen had a strong inhibitory effect on key adipogenic genes in non-ovariectomized female and ovx-female mice supplemented with estrogen. Finally, we show that male and ovariectomized female mice consuming the high-fat diet had a higher incidence of glucose intolerance.

Conclusion

Estrogen protects female mice from obesity and impaired glucose tolerance possibly by modulating the expression of genes regulating adipogenesis, lipogenesis, and lipolysis.     

High Fructose and High Fat Exert Different Effects on Changes in Trabecular Bone Micro-structure

Objectives

To compare the effects of high-fat diet (HFD) and high-fructose diet (HFrD) on bone metabolism at different time points, dynamically observe the bone histology and femur trabecular micro-architecture, and analyze the underlying mechanisms.

Methods

Sixty–Five male 6- to 7-week-old C57BL/6J mice were given HFD, HFrD, or standard diets (SD) for 8, 16, and 24 weeks. Micro-computed tomography (μCT) and bone histology were used to measure bone mass and trabecular micro-structure. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of genes related to bone and lipid metabolisms.

Results

Compared to SD mice, femoral trabecular bone mass was significantly increased in both HFrD mice and HFD mice at 8 weeks, it continued to be higher in HFrD mice at 16 and 24 weeks with the highest level at 16 weeks, but it was significantly decreased in HFD mice at 16 and 24 weeks. HFD mice showed more epididymal fat accumulation than HFrD mice. mRNA expression of Runx2 was up-regulated at 8 and 16 weeks, but down-regulated at 24 weeks similarly in both HFrD mice and HFD mice. mRNA expression of MMP9 and CTSK was up-regulated at 8 and 16 weeks in HFD mice, but down-regulated at 24 weeks in both HFrD mice and HFD mice.

Conclusions

Our data indicated that the HFrD and HFD had different modulating effects on bone mass. After short-term feeding, both HFrD and HFD showed positive effects on bone mass; however, after long-term feeding, bone mass was decreased in HFD mice. In contrast, the bone mass was first increased and then decreased in the HFrD mice. On the basis of these findings, we speculated that chronic consumption of fat and fructose would exert detrimental effects on bone mass which might a combination action of body mass, fat mass, and bone formation/bone resorption along with proinflammatory factor and bone marrow environment.

     

High-fat feeding increases hepatic vitamin C synthesis and its circulatory mobilization in mice

Purpose

Vitamin C (vitC) deficiency has been linked to obesity and increased risk of cardiovascular disease and type 2 diabetes. Whereas humans are unable to synthesize vitC and therefore to compensate for increased turnover, we investigated whether mice—independent of dietary vitC—are able to modulate their vitC homeostasis during high-fat (HF) feeding.

Methods

Twenty-five male 5-week-old C57BL/6 mice were fed high- or low-fat diets for 14 weeks. An oral glucose tolerance test (OGTT) was performed after 12 weeks of intervention. Terminal fasting plasma samples were analyzed for insulin, glucose and vitC concentrations. Hepatic vitC concentration and gulonolactone oxidase (GLO) capacity, as a measure of vitC de novo biosynthesis, were analyzed in liver homogenates.

Results

HF diet significantly increased plasma concentrations of vitC compared with a control diet low in fat (P < 0.05). Hepatic de novo biosynthesis of vitC was upregulated (P < 0.05) as measured by GLO capacity, and liver vitC was reduced (P < 0.01) by HF feeding compared with low-fat feeding. Moreover, plasma concentration of vitC was significantly positively correlated with plasma glucose and insulin concentrations as well as glucose intolerance as measured by an OGTT (P < 0.05).

Conclusion

Our data suggest that mice have the ability to adapt to increased vitC turnover induced by HF diet by increasing hepatic de novo synthesis and mobilization.     

High-fat diets affect energy and bone metabolism in growing rats

Background

High-fat diets are usually associated with greater weight (W) gain and body fat (BF). However, it is still unclear whether the type and amount of fat consumed influence BF. Additionally, dietary fat intake may also have consequences on skeletal health.

Objective

To evaluate in healthy growing rats the effects of high-fat diets and type of dietary fat intake (saturated or vegetable oils) on energy and bone metabolism.

Methods

At weaning, male Wistar rats (n?=?50) were fed either a control diet (C; fat?=?7% w/w) or a high-fat diet (20% w/w) containing either: soybean oil, corn oil (CO), linseed oil (LO), or beef tallow (BT) for 8?weeks. Zoometric parameters, BF, food intake and digestibility, and total and bone alkaline phosphatase (b-AP) were assessed. Total skeleton bone mineral density (BMD) and content (BMC), BMC/W, spine BMD, and bone volume (static-histomorphometry) were measured.

Results

Animals fed BT diet achieved lower W versus C. Rats fed high-fat vegetable oil diets showed similar effects on the zoometric parameters but differed in BF. BT showed the lowest lipid digestibility and BMC. In contrast, high vegetable oil diets produced no significant differences in BMC, BMC/W, BMD, spine BMD, and bone volume. Marked differences were observed for LO and BT groups in b-AP and CO and BT groups in bone volume.

Conclusion

BT diet rich in saturated fatty acids had decreased digestibility and adversely affected energy and bone metabolisms, in growing healthy male rats. There were no changes in zoometric and bone parameters among rats fed high vegetable oil diets.     

Effect of dietary fatty acid composition on substrate utilization and body weight maintenance in humans

Background/purpose

Dietary fat content is a primary factor associated with the increase in global obesity rates. There is a delay in achieving fat balance following exposure to a high-fat (HF) diet (≥ 40 % of total energy from fat) and fat balance is closely linked to energy balance. Exercise has been shown to improve this rate of adaptation to a HF diet. Recently, however, the role of dietary fatty acid composition on energy and macronutrient balance has come into question.

Methods

We chose studies that compared monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and saturated fatty acids (SFA). We have reviewed studies that measured diet-induced thermogenesis (DIT), energy expenditure (EE), or fat oxidation (FOx) in response to a HF meal challenge, or long-term dietary intervention comparing these fatty acids.

Results

While single-meal studies show that SFA induce lower DIT and FOx compared to unsaturated fats, the effect of the degree of unsaturation (MUFA vs. PUFA) appears to yet be determined. Long-term dietary interventions also support the notion that unsaturated fats induce greater EE, DIT, and/or FOx versus SFA and that a high MUFA diet induces more weight loss compared to a high SFA diet. Sex and BMI status also affect the metabolic responses to different fatty acids; however, more research in these areas is warranted.

Conclusion

SFA are likely more obesigenic than MUFA, and PUFA. The unsaturated fats appear to be more metabolically beneficial, specifically MUFA ≥ PUFA > SFA, as evidenced by the higher DIT and FOx following HF meals or diets.     

Adipocyte gene expression is altered in formerly obese mice and as a function of diet composition

In the development of obesity, the source of excess energy may influence appetite and metabolism. To determine the effects of differences in diet composition in obesity, mice were fed either a high-carbohydrate diet (HC; 10% fat energy) or a high-fat energy-restricted diet (HFR; 60% fat energy) over 18 wk in weight-matched groups of mice. To identify obesity-associated genes with persistently altered expression following weight reduction, mice were fed either a standard low-fat diet (LF; 10% fat energy), an unrestricted high-fat diet (HF; 60% fat energy), or a HF diet followed by weight reduction (WR). Mice fed a HF diet had significantly greater gonadal fat mass and higher whole blood glucose concentrations than mice fed an HC diet. Of the mice fed a high-fat diet, total body weight and serum insulin concentrations were greater in HF than in HFR. Microarray analysis revealed that HF vs. HC feeding resulted in global differences in adipocyte gene expression patterns. Although we identified genes whose expression was altered in both moderately and severely obese mice, there were also a large number of genes with altered expression only in severe obesity. Formerly obese, WR mice did not differ significantly from lean controls in total body weight or physiological measures. However, microarray analysis revealed distinctly different patterns of adipocyte gene expression. Furthermore, there were 398 genes with altered expression in HF mice that persisted in WR mice. Genes with persistently altered expression following obesity may play a role in rebound weight gain following weight reduction.     

Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice

Background

Lead (Pb) exposure and obesity are co-occurring risk factors for decreased bone mass in the young, particularly in low socioeconomic communities.

Objectives

The goal of this study was to determine whether the comorbidities of Pb exposure and high-fat diet–induced obesity amplify skeletal deficits independently associated with each of these risk factors, and to explore associated mechanisms of the observed deficiencies.

Methods

Five-week-old male C57BL/6J mice were placed on low-fat (10% kcal, LFD) or high-fat (60% kcal, HFD) diets for 12 weeks. Mice were exposed to lifetime Pb (50 ppm) through drinking water.

Results

HFD was associated with increased body mass and glucose intolerance. Both HFD and Pb increased fasting glucose and serum leptin levels. Pb and HFD each reduced trabecular bone quality and together had a further detrimental effect on these bone parameters. Mechanical bone properties of strength were depressed in Pb-exposed bones, but HFD had no significant effect. Both Pb and HFD altered progenitor cell differentiation, promoting osteoclastogenesis and increasing adipogenesis while suppressing osteoblastogenesis. In support of this lineage shift being mediated through altered Wnt signaling, Pb and non-esterified fatty acids in MC3T3 cells increased in vitro PPAR-γ activity and inhibited β-catenin activity. Combining Pb and non-esterified fatty acids enhanced these effects.

Conclusions

Pb and HFD produced selective deficits in bone accrual that were associated with alterations in progenitor cell activity that may involve reduced Wnt signaling. This study emphasizes the need to assess toxicants together with other risk factors relevant to human health and disease.

Citation

Beier EE, Inzana JA, Sheu TJ, Shu L, Puzas JE, Mooney RA. 2015. Effects of combined exposure to lead and high-fat diet on bone quality in juvenile male mice. Environ Health Perspect 123:935–943; http://dx.doi.org/10.1289/ehp.1408581     

Differential effects of high-fat-diet rich in lard oil or soybean oil on osteopontin expression and inflammation of adipose tissue in diet-induced obese rats

Purpose

To examine the effect of different dietary fat types on osteopontin (OPN) expressions and inflammation of adipose tissues in diet-induced obese rats.

Methods

Male Sprague–Dawley rats were randomly assigned to one control group fed standard diet (LF, n = 10) and two high-fat diet groups fed isoenergy diet rich in lard or soybean oil (HL or HS, n = 45 each). Diet-induced obese rats in HL and HS group were then subdivided into two groups either continuously fed high-fat diet or switched to low-fat diet for 8 more weeks. Fasting serum glucose, insulin, and OPN concentrations were assayed and QUICKI was calculated; the expression of OPN, IL-6, IL-10, TNF-α, NF-κB, and F4/80 in adipose tissue was determined.

Results

Both high-fat diets lead to comparable development of obesity characterized by insulin resistance and adipose tissue inflammation. Obese rats continuously fed high-fat diet rich in lard oil exhibited the highest fasting serum insulin level and adipose tissue OPN, F4/80, TNF-α, and NF-κB expression level. In both high-fat diet groups, switching to low-fat diet resulted in less intra-abdominal fat mass, decreased expression of F4/80, TNF-α, and NF-κB, while decreased OPN expression was only observed in lard oil fed rats after switching to low-fat diet.

Conclusions

Reducing diet fat or replacing lard oil with soybean oil in high-fat diet alleviates obesity-related inflammation and insulin resistance by attenuating the upregulation of OPN and macrophage infiltration into adipose tissue induced by high-fat diet.     

Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes

Background

Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue.

Methods

The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6) leading to rapid obesity development, or selected for high treadmill performance (DUhTP) leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein), or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein) or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein) for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways.

Results

Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor β protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue.

Conclusions

A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.     

Sex-specific association of rs16996148 SNP in the NCAN/CILP2/PBX4 and serum lipid levels in the Mulao and Han populations

Background

This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines.

Methods

Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \ groups (control, colitis, HFD and colitis + HFD).

Results

Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group.

Conclusion

Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream.     

Arctiin inhibits adipogenesis in 3T3-L1 cells and decreases adiposity and body weight in mice fed a high-fat diet

BACKGROUND/OBJECTIVES

The purpose of this study was to examine the effects and associated mechanisms of arctiin, a lignan compound found in burdock, on adipogenesis in 3T3-L1 cells. Also, the effects of arctiin supplementation in obese mice fed a high-fat diet on adiposity were examined.

MATERIALS/METHODS

3T3-L1 cells were treated with arctiin (12.5 to 100 µM) during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes related to adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were first fed either a control diet (CON) or high-fat diet (HF) to induce obesity, and then fed CON, HF, or HF with 500 mg/kg BW arctiin (HF + AC) for four weeks.

RESULTS

Arctiin treatment to 3T3-L1 pre-adipocytes markedly decreased adipogenesis in a dose-dependent manner. The arctiin treatment significantly decreased the protein levels of the key adipogenic regulators PPARγ and C/EBPα, and also significantly inhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatly increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoA carboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fat diet. The epididymal, perirenal or total visceral adipose tissue weights of mice were all significantly lower in the HF + AC than in the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal adipose tissue.

CONCLUSIONS

Arctiin inhibited adipogenesis in 3T3-L1 adipocytes through the inhibition of PPARγ and C/EBPα and the activation of AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing obesity.     

Plasma homocysteine level and hepatic sulfur amino acid metabolism in mice fed a high-fat diet

Purpose

Obesity, a feature of metabolic syndrome, is a risk factor for cardiovascular disease, and elevated plasma homocysteine is associated with increased cardiovascular risk. However, little published information is available concerning the effect of obesity on homocysteine metabolism.

Methods

Hepatic homocysteine metabolism was determined in male C57BL/6 mice fed a high-fat diet for 12 weeks.

Results

High-fat diet increased plasma homocysteine but decreased hepatic homocysteine levels. Hepatic S-adenosylhomocysteine hydrolase levels were down-regulated in the obese mice, which was in part responsible for the decrease in hepatic S-adenosylmethionine/S-adenosylhomocysteine, which served as an index of transmethylation potential. Despite the decrease in hepatic cysteine, hepatic taurine synthesis was activated via up-regulation of cysteine dioxygenase. Hepatic levels of methionine adenosyltransferase I/III, methionine synthase, methylene tetrahydrofolate reductase, and gamma-glutamylcysteine ligase catalytic subunit were unchanged. Obese mice showed elevated betaine-homocysteine methyltransferase and decreased cystathionine beta-synthase activities, although the quantities of these enzymes were unchanged.

Conclusion

This study suggests that plasma homocysteine level is increased in obesity-associated hepatic steatosis, possibly as a result of increased hepatic homocysteine efflux along with an altered sulfur amino acid metabolism.     

Effects of dietary inulin, statin, and their co-treatment on hyperlipidemia, hepatic steatosis and changes in drug-metabolizing enzymes in rats fed a high-fat and high-sucrose diet

Background

Rats fed a high-fat and high-sucrose (HF) diet develop hepatic steatosis and hyperlipidemia. There are several reports that a change in nutritional status affects hepatic levels of drug-metabolizing enzymes. Synthetic inulin is a dietary component that completely evades glucide digestion. Supplementing a HF diet with inulin ameliorates hypertriglycemia and hepatic steatosis, but not hypercholesterolemia. This study aimed at distinguishing the effects of synthetic inulin and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), which inhibit cholesterol biosynthesis.

Methods

We examined effects of co-treatment with synthetic inulin (5%) and fluvastatin (0, 4, and 8 mg/kg, per os) on body weight, epidydimal white adipose tissue weight, serum and hepatic lipid profiles, and hepatic cytochrome P450 (CYP) mRNA and protein profiles in rats fed a standard diet or a HF diet for 3 weeks.

Results

Treatment with the synthetic inulin (5%) or fluvastatin at 4 mg/kg (lethal dose in rats fed the HF diet, 8 mg/kg) ameliorated the elevation in hepatic triacylglycerol and total cholesterol levels in rats fed the HF diet. Whereas co-treatment with the inulin (5%) and fluvastatin (4 mg/kg) had a tendency to more strongly suppress the elevation in serum levels of very low density lipoprotein triacylglycerol than either treatment alone, no additive or synergistic effect was found in decrease in hepatic lipid levels. Hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein and methoxyresorufin O-demethylase and ethoxyresorufin O-deethylase activities were reduced in rats fed the HF diet. The synthetic inulin alleviated the reduction in hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein more strongly than fluvastatin, and no synergistic effects were observed on co-treatment. Furthermore, hepatic levels of aryl hydrocarbon receptor mRNA were decreased in rats fed the HF diet and recovered to near normal values with the intake of dietary inulin, which correlated with change in CYP1A1/2.

Conclusions

Dietary inulin alone was effective to prevent the development of hepatic steatosis, ameliorate nutritional effects, and alleviate the hepatic change in the expression of CYP1A1/2 and CYP2E1, while co-treatment with statin did not have additive or synergistic effects and statin may cause adverse effects in rats fed the HF diet.     

Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats

Background

Fruits and nuts may prevent or reverse common human health conditions such as obesity, diabetes and hypertension; together, these conditions are referred to as metabolic syndrome, an increasing problem. This study has investigated the responses to ellagic acid, present in many fruits and nuts, in a diet-induced rat model of metabolic syndrome.

Methods

Eight- to nine-week-old male Wistar rats were divided into four groups for 16-week feeding with cornstarch diet (C), cornstarch diet supplemented with ellagic acid (CE), high-carbohydrate, high-fat diet (H) and high-carbohydrate, high-fat diet supplemented with ellagic acid (HE). CE and HE rats were given 0.8 g/kg ellagic acid in food from week 8 to 16 only. At the end of 16 weeks, cardiovascular, hepatic and metabolic parameters along with protein levels of Nrf2, NF-κB and CPT1 in the heart and the liver were characterised.

Results

High-carbohydrate, high-fat diet-fed rats developed cardiovascular remodelling, impaired ventricular function, impaired glucose tolerance, non-alcoholic fatty liver disease with increased protein levels of NF-κB and decreased protein levels of Nrf2 and CPT1 in the heart and the liver. Ellagic acid attenuated these diet-induced symptoms of metabolic syndrome with normalisation of protein levels of Nrf2, NF-κB and CPT1.

Conclusions

Ellagic acid derived from nuts and fruits such as raspberries and pomegranates may provide a useful dietary supplement to decrease the characteristic changes in metabolism and in cardiac and hepatic structure and function induced by a high-carbohydrate, high-fat diet by suppressing oxidative stress and inflammation.     

Pomegranate and its derivatives can improve bone health through decreased inflammation and oxidative stress in an animal model of postmenopausal osteoporosis

Purpose

Recently, nutritional and pharmaceutical benefits of pomegranate (PG) have raised a growing scientific interest. Since PG is endowed with anti-inflammatory and antioxidant activities, we hypothesized that it may have beneficial effects on osteoporosis.

Methods

We used ovariectomized (OVX) mice as a well-described model of postmenopausal osteoporosis to study the influence of PG consumption on bone health. Mice were divided into five groups as following: two control groups sham-operated and ovariectomized (OVX CT) mice fed a standard diet, versus three treated groups OVX mice given a modified diet from the AIN-93G diet, containing 5.7 % of PG lyophilized mashed totum (OVX PGt), or 9.6 % of PG fresh juice (OVX PGj) or 2.9 % of PG lyophilized mashed peel (OVX PGp).

Results

As expected, ovariectomy was associated with a decreased femoral bone mineral density (BMD) and impaired bone micro-architecture parameters. Consumption of PGj, PGp, or PGt induced bone-sparing effects in those OVX mice, both on femoral BMD and bone micro-architecture parameters. In addition, PG (whatever the part) up-regulated osteoblast activity and decreased the expression of osteoclast markers, when compared to what was observed in OVX CT animals. Consistent with the data related to bone parameters, PG consumption elicited a lower expression of pro-inflammatory makers and of enzymes involved in ROS generation, whereas the expression of anti-inflammatory markers and anti-oxidant actors was enhanced.

Conclusion

These results indicate that all PG parts are effective in preventing the development of bone loss induced by ovariectomy in mice. Such an effect could be partially explained by an improved inflammatory and oxidative status.     

Nutrient reference values for bioactives: new approaches needed? A conference report

Purpose

To comprehensively review the data on the relationship between the consumption of dairy fat and high-fat dairy foods, obesity, and cardiometabolic disease.

Methods

We have conducted a systematic literature review of observational studies on the relationship between dairy fat and high-fat dairy foods, obesity, and cardiometabolic disease. We have integrated these findings with data from controlled studies showing effects of several minor dairy fatty acids on adiposity and cardiometabolic risk factors, and data on how bovine feeding practices influence the composition of dairy fat.

Results

In 11 of 16 studies, high-fat dairy intake was inversely associated with measures of adiposity. Studies examining the relationship between high-fat dairy consumption and metabolic health reported either an inverse or no association. Studies investigating the connection between high-fat dairy intake and diabetes or cardiovascular disease incidence were inconsistent. We discuss factors that may have contributed to the variability between studies, including differences in (1) the potential for residual confounding; (2) the types of high-fat dairy foods consumed; and (3) bovine feeding practices (pasture- vs. grain-based) known to influence the composition of dairy fat.

Conclusions

The observational evidence does not support the hypothesis that dairy fat or high-fat dairy foods contribute to obesity or cardiometabolic risk, and suggests that high-fat dairy consumption within typical dietary patterns is inversely associated with obesity risk. Although not conclusive, these findings may provide a rationale for future research into the bioactive properties of dairy fat and the impact of bovine feeding practices on the health effects of dairy fat.     

Inhibitory effects of Doenjang,Korean traditional fermented soybean paste,on oxidative stress and inflammation in adipose tissue of mice fed a high-fat diet

BACKGROUND/OBJECTIVES

Doenjang, Korean traditional fermented soybean paste has been reported to have an anti-obesity effect. Because adipose tissue is considered a major source of inflammatory signals, we investigated the protective effects of Doenjang and steamed soybean on oxidative stress and inflammation in adipose tissue of diet-induced obese mice.

MATERIALS/METHODS

Male C57BL/6J mice were fed a low fat diet (LF), a high-fat diet (HF), or a high-fat containing Doenjang diet (DJ) or a high-fat containing steamed soybean diet (SS) for 11 weeks.

RESULTS

Mice fed a DJ diet showed significantly lower body and adipose tissue weights than those in the HF group. Although no significant differences in adipocyte size and number were observed among the HF diet-fed groups, consumption of Doenjang alleviated the incidence of crown-like structures in adipose tissue. Consistently, we observed significantly reduced mRNA levels of oxidative stress markers (heme oxygenase-1 and p40^phox), pro-inflammatory adipokines (tumor necrosis factor alpha and macrophage chemoattractant protein-1), macrophage markers (CD68 and CD11c), and a fibrosis marker (transforming growth factor beta 1) by Doenjang consumption. Gene expression of anti-inflammatory adipokine, adiponectin was significantly induced in the DJ group and the SS group compared to the HF group. The anti-oxidative stress and anti-inflammatory effects observed in mice fed an SS diet were not as effective as those in mice fed a DJ diet, suggesting that the bioactive compounds produced during fermentation and aging may be involved in the observed health-beneficial effects of Doenjang.

CONCLUSIONS

Doenjang alleviated oxidative stress and restored the dysregulated expression of adipokine genes caused by excess adiposity. Therefore, Doenjang may ameliorate systemic inflammation and oxidative stress in obesity via inhibition of inflammatory signals of adipose tissue.