Red grape berry-cultured cells reduce blood pressure in rats with metabolic-like syndrome

Purpose

Cumulative evidence suggests that moderate red wine consumption protects the cardiovascular system. The effect of cultured cells derived from red grape berry (RGC) on blood pressure (BP) has not been investigated. We therefore studied the antihypertensive effects of oral consumption of RGC in experimental rat model of metabolic-like syndrome and assessed its effect on human umbilical vein endothelial cells (HUVECs).

Methods

Forty male Sprague–Dawley rats were fed for 5 weeks with either a high fructose diet (HFD) (n = 10) or HFD supplemented, during the last 2 weeks, with different doses (200, 400 and 800 mg/kg/day) of RGC suspended in their food (n = 30). BP, plasma triglycerides, insulin and adiponectin levels were measured at the beginning and after 3 and 5 weeks of diet. RGC effect on vasodilatation was evaluated by its ability to affect endothelin-1 (ET-1) production and endothelial nitric oxide synthase (eNOS) expression in HUVECs.

Results

BP, plasma triglycerides, insulin and adiponectin increased significantly in rats fed with a HFD. The increase in BP, plasma triglycerides and insulin was attenuated by RGC supplementation. Incubation of HUVECs with RGC demonstrated a concentration-dependent inhibition of ET-1 secretion and increase in the level of eNOS, signaling a positive effect of RGC on vasodilatation.

Conclusion

In rats with metabolic-like syndrome, RGC decreased BP and improved metabolic parameters. These beneficial effects may be mediated by the cell constituents, highly rich with polyphenols and resveratrol, reside in their natural state.     

Cranberry (<Emphasis Type="Italic">Vaccinium macrocarpon</Emphasis>) extract treatment improves triglyceridemia,liver cholesterol,liver steatosis,oxidative damage and corticosteronemia in rats rendered obese by high fat diet

Purpose

Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model.

Methods

At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed.

Results

HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group.

Conclusion

Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.

     

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.     

Antioxidant activity of whole grain highland hull-less barley and its effect on liver protein expression profiles in rats fed with high-fat diets

Purpose

Whole grain exhibits potential for regulating lipid levels, possibly because of its antioxidant activity. This study aims to investigate the antioxidant activity of whole grain highland hull-less barley (WHLB) and its effect on liver protein expression profiles in rats fed with high-fat diets.

Methods

Antioxidant activity of WHLB was investigated in vitro by analyzing phenolic and pentosan contents and oxygen radical absorbance capacity (ORAC). Proteins involved in lipid regulation were investigated in vivo by analyzing liver protein expression profiles in Sprague–Dawley rats fed with high-fat diet (HFD) with or without WHLB.

Results

WHLB possessed high total phenolic content (259.90 mg/100 g), total pentosan content (10.74 g/100 g), and ORAC values (418.05 ± 5.65 μmol/g). Rats fed with WHLB diet exhibited significantly (P < 0.05) lower liver lipid levels than those fed with the control HFD diet. Seven differentially expressed proteins were detected through liver proteome analysis and were found to be correlated with 11 pathways, including lipid metabolism, through annotation with Kyoto Encyclopedia of Genes and Genomes. Quantitative real-time polymerase chain reaction analysis showed that rats given with WHLB diet exhibited down-regulated expression of heat shock protein 60 (HSP60) and phosphatidylethanolamine binding protein 1 (PEBP1) and up-regulated expression of enoyl-coenzyme A hydratase (ECH) and peroxiredoxin 6 (PRDX6).

Conclusions

HSP60, PEBP1, ECH, and PRDX6 may be involved in the lipid regulatory effect of WHLB. Moreover, the regulation of PRDX6 may be related to the antioxidant activity of WHLB.

     

Diet-induced obese rats have higher iron requirements and are more vulnerable to iron deficiency

Purpose

Since obesity is associated with poorer iron status, the effects of diet-induced obesity on iron status and iron-regulatory pathways were examined.

Methods

Weanling male diet-induced obese sensitive (n = 12/diet group) and resistant (n = 12/diet group) rats were fed one of four high-fat, high-energy diets supplemented with 5 (5Fe, low), 15 (15Fe, marginal), 35 (35Fe, normal) or 70 (70Fe, high) mg iron/kg diet for 12 weeks. At the end of the study, rats in each diet group were categorised as obese (>19 %) or lean (<17 %) based on percentage body fat.

Results

Obese rats gained more weight, had larger total lean mass, consumed more food and showed greater feed efficiency compared with lean rats. Obese rats fed the 5Fe and 15Fe diets had poorer iron status than lean rats fed the same diet. Obese 5Fe rats had lower serum iron and more severe iron-deficiency anaemia. Obese 15Fe rats had lower mean corpuscular haemoglobin and liver iron concentrations. Hepcidin mRNA expression in liver and adipose tissue was similar for obese and lean rats. Iron concentration and content of the iron transporters divalent metal transporter 1 and ferroportin 1 in duodenal mucosa were also similar.

Conclusions

Obese rats that were larger, regardless of adiposity, had higher iron requirements compared with lean rats that appeared independent of hepcidin, inflammation and intestinal iron absorption. Higher iron requirements may have resulted from larger accretion of body mass and blood volume. Greater food consumption did not compensate for the higher iron needs, indicating increased susceptibility to iron deficiency.     

Consumption of wheat bran modified by autoclaving reduces fat mass in hamsters

Purpose

To investigate the effect that wheat bran modified by autoclaving (MWB) had on reducing fat accumulation in hamsters fed a hypercholesterolemia- and obesity-inducing diet.

Methods

Male hamsters (n = 45) were randomized into 3 groups and fed a hypercholesterolemia- and obesity-inducing diet with or without 10 % standard wheat bran or MWB for 28 days. Our outcome measures included body composition measured by DXA, oxygen consumption and plasma lipids and glucose concentrations.

Results

Animals fed the MWB diet had lower % fat mass (49.8 vs. 53.4 %; p = 0.02) and higher % lean body mass (47.2 vs. 44.1 %; p = 0.02) compared with controls despite no differences in food intake or weight gain. Additionally, plasma glucose tended to be lower (6.9 vs. 8.5 mmol/l; p < 0.08) in the MWB animals compared with controls.

Conclusions

Our data suggest that the compositional changes in autoclaved wheat bran, specifically solubility of phenolic antioxidants and fiber, may have contributed to the lower fat accumulation in our animals. Further study is needed to determine whether the exact mechanism involved increased lipolysis and energy utilization from adipose.     

High dietary taurine inhibits myocardial apoptosis during an atherogenic diet: association with increased myocardial HSP70 and HSF-1 but not caspase 3

Background and aim

Apoptosis is a major cause of myocyte death, and taurine is anti-apoptotic. Heat shock protein 70 (HSP70) (which is regulated by heat shock factor—HSF-1) is also anti-apoptotic, and caspase 3 stimulates the apoptotic pathway. This study investigated whether taurine affects atherogenic diet-induced myocardial apoptosis, and whether HSP70, HSF-1 and caspase 3 are involved.

Methods

New Zealand white rabbits were divided into 3 groups for 4 weeks according to their diet. Group 1 (control) was fed a normal rabbit diet; Group 2 (MC) received a normal rabbit diet with 1 % methionine plus 0.5 % cholesterol. Group 3 received MC diet + 2.5 % taurine (MCT).

Results

The atherogenic diet did not affect myocardial HSP70 or HSF-1 protein, but increased myocardial apoptotic nuclei to 40 % (p < 0.01) versus 7 % in con and 12 % in MCT (p < 0.01). However, in MCT, myocardial HSP70 expression increased by 42.7 % versus con and MC (p = 0.016), HSF-1 by 12 % versus con and MC (p < 0.05), and total nuclei count increased by 37 % versus MC (p < 0.05). Caspase 3 subunits remained unchanged in all groups, and HSP70 was increased approximately twofold in endothelial layer of arterioles (p = 0.01).

Conclusion

This study shows that taurine could reduce myocardial apoptotic nuclei and thus confer myocardial cytoprotection via stimulating myocardial HSP70 via HSF-1 and caspase 3-independent mechanisms.     

Cardioprotective and hepatoprotective effects of ellagitannins from European oak bark (Quercus petraea L.) extract in rats

Background

Red wine contains many potentially bioactive polyphenols including resveratrol, catechins, anthocyanins and flavonoids as well as tannins derived from oak during maturation. This study examined the effects of a mixture of ellagitannins from oak bark (Quercus petraea L.) on cardiovascular, metabolic and liver changes in high-carbohydrate, high-fat diet–fed rats and in Spontaneously Hypertensive Rats (SHR).

Methods

First, 8-week-old male Wistar rats were divided into four groups and given either cornstarch diet, cornstarch diet + oak bark extract (0.5 mL/kg food), high-carbohydrate, high-fat diet or high-carbohydrate, high-fat diet + oak bark extract (0.5 mL/kg food) for 16 weeks. Oak bark extract was added to the diets for last 8 weeks of the feeding period. Secondly, SHR aged 42 weeks fed on standard chow diet were divided into two groups with and without oak bark extract treatment for 12 weeks (0.5 mL/kg food).

Results

The high-carbohydrate, high-fat diet induced signs of metabolic syndrome along with cardiovascular remodelling and non-alcoholic steatohepatitis. Oak bark extract attenuated the signs of metabolic syndrome in high-carbohydrate, high-fat diet–fed rats and improved the structure and function of the heart and the liver. SHR after oak bark extract treatment for 12 weeks showed lower systolic blood pressure, lower cardiac fibrosis and cardiac stiffness and improved vascular reactivity.

Conclusions

Oak bark extract containing ellagitannins improved cardiovascular, metabolic and liver parameters in these rat models of human disease, suggesting that part of the benefits attributed to red wine may be produced by these ellagitannins.     

Low dietary calcium and obesity: a comparative study in genetically obese and normal rats during early growth

Purpose

A low calcium intake (LCaI) may predispose to obesity, and excessive fat mass may be detrimental to bone. The impact of Ca inadequacy would be greater in subjects predisposed to obesity. LCaI effect on obesity development during the rapid growth period was compared in two strains of rats: spontaneously obese IIMb/β (O) and Wistar (W). Pregnant rats were fed 0.5 % (N) or 0.2 % (L) of Ca (OLCa, ONCa, WLCa and WNCa). Male pups were fed the maternal diet until day 60.

Methods

Body composition, lipid profile, glucose homeostasis, 25 hydroxyvitamin D, Ca-phosphorus, and bone metabolism were evaluated.

Results

BW and body fat were higher, whereas body protein was lower in OLCa versus ONCa (p < 0.05). OLCa presented the highest body fat, glucose, non-HDL and total cholesterol, TGL, insulin levels, and HOMA-IR, liver weight, and adipose perigonadal plus retroperitoneal pads (p < 0.05). WLCa did not exhibit an increase BW and only showed a slight change in body composition with minor biochemical alterations compared to WNCa (p < 0.05). Osteocalcin, CTX, and proximal tibia and lumbar spine BMDs were lower in O than in W rats fed the same Ca diet (p < 0.05). Body ash and Ca content, and total skeleton BMC/BW were lower in OLCa and WLCa versus their corresponding NCa groups (p < 0.05).

Conclusion

The negative effect of a low Ca diet on fat mass accumulation and lipid profile may be more evident in rats predisposed to obesity. Nevertheless, low CaI interferes with the normal glucose homeostasis leading to an increase in insulin resistance. Low CaI during early growth may be an obesogenic factor that may persist into adult life and may account for the development of obesity and some of its co-morbidities.     

Effects of endurance training on autophagy and apoptotic signaling in visceral adipose tissue of prolonged high fat diet-fed rats

Purpose

Autophagy and apoptosis play critical roles in both development and tissue homeostasis in response to (patho)physiological stimuli, such as high-fat diet (HFD) and endurance training (ET). Therefore, we aimed to investigate how ET modulates autophagy and apoptotic-related signaling in visceral adipose tissue of long-standing HFD-fed rats.

Methods

The study was conducted over a 17-week period on Sprague–Dawley rats, which were divided into four groups (n = 8/group): standard diet sedentary (STD+SED), high-fat diet sedentary (HFD+SED), standard diet ET (STD+ET) and high-fat diet ET (HFD+ET). After 9 weeks of dietary regimens, ET groups were trained for 8 weeks on treadmill (5 days/week at 25 m/min for 60 min/day), while maintaining dietary regimens. Autophagy and apoptotic-signaling markers in epididymal white adipose tissue (eWAT) were determined using RT-qPCR, Western blot and spectrometry techniques.

Results

ET reduced body weight, visceral fat mass and HOMA-IR in standard and HF diet-fed animals. Moreover, ET reverted the HFD-induced increases in the percentage of larger adipocytes and also reduced the percentage of smaller adipocytes. The HFD decreased pre-adipocyte factor 1 (DLK1/PREF1) and increased the pro-apoptotic markers (Bax protein and caspase 3-like activity), while having no impact on autophagy markers. However, ET increased DLK1/PREF1 and Bcl-2 in both diet types, while decreasing Bax and caspases 9, 8 and 3-like activities in HFD feeding rats. Additionally, Beclin-1 and p62 protein significantly increased in ET groups of both diet types.

Conclusions

Data demonstrate that 8 weeks of ET was effective in attenuating apoptotic-related signaling in long-standing HFD-fed rats. Moreover, HFD and ET had no impact on VAT autophagy markers.

     

Evidence of altered biochemical composition in the hearts of adult intrauterine growth-restricted rats

Purpose

Epidemiological studies clearly link intrauterine growth restriction with increased risk of cardiac disease in adulthood. The mechanisms leading to this increased risk are poorly understood; remodeling of the myocardium is implicated. The aim was to determine the effect of early life growth restriction on the biochemical composition of the left ventricular myocardium in adult rats.

Methods

Wistar Kyoto dams were fed either a low protein diet (LPD; 8.7 % casein) or normal protein diet (NPD; 20 % casein) during pregnancy and lactation; from weaning, the offspring were fed normal rat chow. At 18 weeks of age, the biochemical composition of the hearts of NPD control (n = 9) and LPD intrauterine growth-restricted (n = 7) offspring was analyzed using Fourier Transform Infrared (FTIR) micro-spectroscopy.

Results

Body weights at postnatal day 4 were significantly lower and remained lower throughout the experimental period in the LPD offspring compared to controls. FTIR analysis of the infrared absorption spectra across the whole “fingerprint” region (1,800–950 cm^?1) demonstrated wider variation in absorbance intensity in the LPD group compared to controls. In particular, there were marked differences detected in the protein (1,540 cm^?1), lipid (1,455 and 1,388 cm^?1), proteoglycan (1,228 cm^?1) and carbohydrate (1,038 cm^?1) bands, indicating increased lipid, proteoglycan and carbohydrate content in the growth-restricted myocardium.

Conclusion

In conclusion, changes in the biochemical composition of the myocardium provide a likely mechanism for the increased vulnerability to cardiovascular disease in offspring that were growth restricted in early life.     

Impact of a functionalized olive oil extract on the uterus and the bone in a model of postmenopausal osteoporosis

Purpose

The Mediterranean diet rich in fruits, vegetables and olive oil has been related to a lower osteoporosis incidence and accordingly to a reduced fracture risk. These observations might be mediated by the active constituents of extra virgin olive oil, and especially polyphenols. In the context of exploring the features of olive oil active constituents on postmenopausal osteoporosis, an extra virgin olive oil total polyphenolic fraction (TPF) was isolated and its effect on the bone loss attenuation was investigated.

Methods

Female Lewis rats were ovariectomized and fed a diet enriched with a total phenolic extract of extra virgin olive oil in a concentration of 800 mg/kg diet.

Results

Oleocanthal, one compound of the polyphenolic fraction, showed a higher relative estrogen receptor binding affinity to the ERα compared to the ERβ. While the TPF only slightly induced the uterine wet weight (490.7 ± 53.7 vs. 432.7 ± 23, p = 0.058), TPF regulated estrogen response genes in the uterus (progesterone receptor, antigen identified by monoclonal antibody Ki67, complement C3). Comparing the quantified bone parameters, the oral TPF substitution did not attenuate the ovariectomy-induced bone loss.

Conclusions

The administration of extra virgin olive oil polyphenols regulated uterine estrogen response marker genes in an E2-agonistic manner. The bone loss induced by estrogen ablation was not mitigated by treatment with the polyphenolic extract.     

Effect of dietary calcium (Ca) on body composition and Ca metabolism during growth in genetically obese (β) male rats

Introduction

Obese β rats may be a suitable model to evaluate the association between calcium intake (CaI) and obesity during growth.

Objective

The present study comparatively evaluated Ca absorption and retention, and changes in body composition in spontaneously genetically obese (β) male rats fed three different dietary Ca levels: high 0.9% (HCa); normal: 0.5% (NCa); low: 0.2% (LCa).

Methods

Pregnant rats were fed isocaloric diets which varied in Ca content only. Male pups continued feeding the same maternal diet until postnatal day 60. The percentage of Apparent Ca absorption (CaA %), Ca balance (CaB), body composition, glucose, triglycerides (TGL), and insulin levels were evaluated.

Results

Food consumption and body weight (BW) were higher in Group LCa than in Groups NCa and HCa (p < 0.01); no differences were observed between the latter two groups. Group LCa presented the highest body fat, liver weight, perigonadal and retroperitoneal fat (p < 0.05); conversely, body ashes and total skeleton bone mineral content were significantly lower compared with animals in both the NCa (p < 0.01) and HCa groups (p < 0.01). CaB (mg/day) reached a plateau at the highest CaI (mg/day) value (r = 0.985, p < 0.001). CaA%, serum glucose, insulin, and TGL levels rose as CaI decreased (p < 0.01).

Conclusions

Although further studies are required, low Ca consumption in this strain of rats could modulate BW inducing changes in several lipid metabolism parameters, which in turn lead to an increase in body fat.     

Chlorella pyrenoidosa ameliorated L-NAME-induced hypertension and cardiorenal remodeling in rats

Purpose

Hypertension is one of the main factors causing cardiovascular diseases. The aim of the study is to investigate the effects of Chlorella pyrenoidosa on blood pressure and cardiorenal remodeling in rats with N _ω-nitro-l-arginine methyl ester hydrochloride (L-NAME)-induced endothelial dysfunction.

Methods

Rats were fed a diet containing L-NAME (40 mg/kg) with or without chlorella (4 or 8 %) for 5 weeks. We found that chlorella retarded the development of hypertension and cardiorenal remodeling during the 5-week experimental period.

Results

Although there was no difference in NO _x levels or plasma arginine concentrations, plasma and tissues ACE activities were significantly lower in the chlorella groups than in the L-NAME group. Moreover, tissue tumor necrosis factor-α concentrations and renal CYP4A expression were also lower in the chlorella group.

Conclusion

These results suggest that chlorella might ameliorate the elevation of blood pressure and show cardiorenal-protective effects in nitric oxide-deficient rats, and one possible mechanism might be mediated by its ACE inhibitory activity.     

Postnatal high-fat diet enhances ectopic fat deposition in pigs with intrauterine growth retardation

Objectives

Intrauterine growth retardation (IUGR) and postnatal nutrition are risk factors for adult metabolic syndrome. However, the influences of long-term high-fat diet (HFD) intake on ectopic fat deposition in non-adipose tissues in IUGR pigs remain unclear. The present study was to determine whether HFD consumption would enhance ectopic fat deposition in IUGR pigs.

Methods

At day 28, IUGR and control pigs were fed ad libitum to either a regular diet or a HFD. Lipid store, enzymatic activities and mRNA expression of lipid metabolism-related factors in liver and semitendinosus muscle (SM) were quantified at postnatal day 178.

Results

Feeding a HFD to IUGR pigs but not to control pigs significantly increased daily weight gain, carcass fat mass, plasma leptin level and lipid content and lipoprotein lipase (LPL) activity and mRNA abundances of LPL and peroxisome proliferator-activated receptor gamma (PPARγ) in liver and SM, but decreased daily feed intake and mRNA expression of hormone-sensitive lipase (LIPE) and carnitine palmitoyl transferase-1 (CPT-1) in liver and SM (P < 0.05). Compared with control pigs, IUGR pigs had a lower body weight but higher plasma levels of total cholesterol (TC) and insulin (P < 0.05). HFD-fed pigs exhibited greater body weight, plasma concentrations of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), regardless of birth weight (P < 0.05).

Conclusion

Our results suggested that IUGR increased the vulnerability of HFD-fed pigs to ectopic fat deposition via enhanced fatty acid flux toward ectopic sites and reduced lipolysis and fatty acid oxidation.

     

Adipose tissue remodeling in rats exhibiting fructose-induced obesity

Purpose

To explore the effect of a fructose-rich diet on morphological and functional changes in white adipose tissue (WAT) that could contribute to the development of insulin resistance.

Methods

Adult sedentary rats were fed a fructose-rich diet for 8 weeks. Glucose tolerance test was carried out together with measurement of plasma triglycerides, non-esterified fatty acids and lipid peroxidation. In subcutaneous abdominal and intra-abdominal WAT, number and size of adipocytes together with cellular insulin sensitivity and lipolytic activity were assessed.

Results

Rats fed a fructose-rich diet exhibited a significant increase in plasma insulin, triglycerides, non-esterified fatty acids and lipid peroxidation, together with significantly increased body lipids and epididymal and mesenteric WAT, compared to controls. Mean adipocyte volume in subcutaneous abdominal WAT was significantly lower, while mean adipocyte volume in intra-abdominal WAT was significantly higher, in rats fed a fructose-rich diet compared to controls. A significant increase in larger adipocytes and a significant decrease in smaller adipocytes were found in intra-abdominal WAT in rats fed a fructose-rich diet compared to controls. Insulin’s ability to inhibit lipolysis was blunted in subcutaneous abdominal and intra-abdominal adipocytes from fructose-fed rats. Accordingly, lower p-Akt/Akt ratio was found in WAT in rats fed a fructose-rich diet compared to controls.

Conclusions

Long-term consumption of high levels of fructose elicits remarkable morphological and functional modifications, particularly in intra-abdominal WAT, that are highly predictive of obesity and insulin resistance and that contribute to the worsening of metabolic alterations peculiar in a fructose-rich, hypolipidic diet.     

Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats

Purpose

Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits.

Methods

The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet.

Results

Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r ² = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r ² = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses.

Conclusion

Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.     

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.     

Increased hepatic de novo lipogenesis and mitochondrial efficiency in a model of obesity induced by diets rich in fructose

Purpose

To assess hepatic de novo lipogenesis and mitochondrial energetics as well as whole-body energy homeostasis in sedentary rats fed a fructose-rich diet.

Methods

Male rats of 90 days of age were fed a high-fructose or control diet for 8 weeks. Body composition, energy balance, oxygen consumption, carbon dioxide production, non-protein respiratory quotient, de novo lipogenesis and insulin resistance were measured. Determination of specific activity of hepatic enzymes of de novo lipogenesis, mitochondrial mass, oxidative capacity and degree of coupling, together with parameters of oxidative stress and antioxidant defence, was also carried out.

Results

Body energy and lipid content as well as plasma insulin and non-esterified fatty acids were significantly higher in fructose-fed than in control rats. Significantly higher rates of net de novo lipogenesis and activities of hepatic lipogenic enzymes fatty acid synthase and stearoyl CoA desaturase-1 were found in fructose-fed rats compared to controls. Mitochondrial protein mass and degree of coupling were significantly higher in fructose-fed rats compared to controls. Hepatic mitochondria showed oxidative damage, both in the lipid and in the protein component, together with decreased activity of antioxidant defence.

Conclusion

Liver mitochondrial compartment is highly affected by fructose feeding. The increased mitochondrial efficiency allows liver cells to burn less substrates to produce ATP for de novo lipogenesis and gluconeogenesis. In addition, increased lipogenesis gives rise to whole body and ectopic lipid deposition, and higher mitochondrial coupling causes mitochondrial oxidative stress.