Ilex paraguariensis (yerba mate) improves endocrine and metabolic disorders in obese rats primed by early weaning

Purpose

We showed that early weaned rats developed obesity, hyperleptinemia, leptin and insulin resistance at adulthood. Here, we studied the potential beneficial effects of Ilex paraguariensis aqueous solution upon body composition, glycemia, lipid and hormonal profiles, leptin signaling and NPY content.

Methods

To induce early weaning, lactating rats’ teats were blocked with a bandage to interrupt lactation during the last 3 days (EW group), while control offspring had free access to milk throughout lactation (C group). In postnatal day (PN) 150, EW offspring were subdivided into: EW and EW+ mate groups treated, respectively, with water or yerba mate aqueous solution (1 g/kg BW/day, gavage) during 30 days. C offspring received water for gavage. In PN180, offspring were killed.

Results

EW+ mate group presented lower body weight (?10 %), adipose mass (retroperitoneal:?40 % and epididymal:?44 %), total body fat (?43 %), subcutaneous fat (?46 %), visceral adipocyte area (?21 %), triglyceridemia (?31 %) and hypothalamic NPY content (?37 %) compared to EW group. However, hyperglycemia and lower HDL-c levels observed in EW group were not reverted with mate treatment. Although the hyperleptinemia, lower hypothalamic JAK2 and pSTAT3 content of EW group were not corrected by mate treatment, the hyperphagia and higher hypothalamic SOCS-3 content were normalized in EW+ mate group, indicating that the central leptin resistance could be restored.

Conclusion

Thus, the therapy with yerba mate solution was capable to reverse abdominal obesity, leptin resistance and hypertriglyceridemia, suggesting an important role of this bioactive component in the management of obesity in this programming model.     

Effect of iodine source and dose on growth and iodine content in tissue and plasma thyroid hormones in fattening pigs

Purpose

The aim of the present feeding trial with iodine was to assess pigs’ growth performance and carcass characteristics, the iodine accumulation in tissues, and their influences on the thyroid hormones in plasma.

Methods

Eighty pigs (33–115?kg body weight) were allotted to 5 dietary treatments: a control group (150?μg I/kg), two potassium iodide [KI] groups (4,000 and 10,000?μg I/kg), and two potassium iodate [KIO₃] groups (4,000 and 10,000?μg I/kg). Iodine concentration was determined in thyroid gland, liver, kidney, muscle, fat, and skin by ICP-MS. Furthermore, thyroxine (T₄) and triiodothyronine (T₃) in plasma were evaluated.

Results

High dietary iodine tended to have a negative effect on younger animals' growth (average daily gain, ADG). However, during the entire growth period, the growth performance and carcass characteristics were not influenced by iodine dosages or sources. Irrespective of iodine source, higher iodine doses of diets affected higher iodine stores in all tested tissues except for abdominal fat. Thus, iodine supplementation with 10,000?μg I/kg feed significantly increased iodine content in thyroid gland (+122%), liver (+260%), kidney (+522%), muscle (+131%), and skin (+321%) compared to the control group. However, there was no significance of thyroid hormones in plasma.

Conclusions

As a result, pork and fat of pigs showed only low iodine accumulation even in the high-iodine groups. Thus, there should be no risk of an iodine excess in human nutrition and animal health, and the EU-upper level for iodine in pig feed can be maintained.     

Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats

Background

Dietary long-chain polyunsaturated fatty acids (LC-PUFA) are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the neonates.

Methods

Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55%) and eicosapentaenoic acid (EPA, 0.75% of total fatty acids) or α-linolenic acid (ALA, 2.90%). At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA) profile. Data were analyzed by bivariate and multivariate statistics.

Results

In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P < 0.0001) and brain glial cell PE (+18%, P = 0.0001) and PS (+15%, P = 0.0009) were significantly increased compared to the ALA group. The filtered correlation analysis (P < 0.05) underlined that levels of dihomo-γ-linolenic acid (DGLA), DHA and n-3 docosapentaenoic acid (DPA) were negatively correlated with arachidonic acid (ARA) and n-6 DPA in PE of brain glial cells. No significant correlation between n-3 and n-6 LC-PUFA were found in the PS dataset. DMA level in PE was negatively correlated with n-6 DPA. DMA were found to occur in brain glial cell PS fraction; in this class DMA level was correlated negatively with DHA and positively with ARA.

Conclusion

The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.     

Moderate physical training attenuates muscle-specific effects on fibre type composition in adult rats submitted to a perinatal maternal low-protein diet

Aim

To verify whether moderate physical training affects the muscle fibre composition of adult rats subjected to a low protein diet during the perinatal period.

Methods

Male Wistar rats were divided into two groups according to their mother’s diet during gestation and lactation: control (17% casein, C) and low-protein (8% casein, LP). On postnatal day 60, half of each group was submitted to moderate physical training (8?weeks, 5?days/week^?1, 60?min/day^?1, at 70% of VO_2max, T) or not. After the physical training period, soleus and extensor digitorum longus (EDL) muscles were removed. Myofibrillar ATPase staining was used to classify muscle fibres as type I, IIa, IIb, and intermediate.

Results

In the EDL muscle, LP rats showed no changes in the fibre type proportion. Both the C?+?T and LP?+?T groups showed a higher percentage of fibres of type IIa, and a lower proportion of fibres of type IIb. In the soleus muscle, LP animals showed a reduction in the proportion of fibre types I and intermediate. C?+?T rats showed an increase in the fibre type I and IIa. In the LP?+?T rats, the proportions of the fibre types remained similar to control rats.

Conclusions

Moderate physical training acts as a positive environmental stimulus that reverts the effects of a perinatal low-protein diet on the proportion of fibre types in skeletal muscle.     

Relation of child birth and breast-feeding burden with cadmium and tubular dysfunction marker levels in urine of adult women in non-polluted areas in Japan

Background and objectives

Cd absorption may be enhanced in association with iron (Fe) deficiency. Women have increased risks of Fe loss at the time of child birth as well as breast-feeding of children. Possible effects of these two factors were investigated in the present study.

Methods

Data were drawn from previous publications from this group on Cd and tubular dysfunction markers (i.e., α₁-microglobulin, β₂-microglobulin, and N-acetyl-β-d-glucosaminidase) in urine of adult women in non-polluted areas in Japan. Information including age, smoking, number of children, and types of child feeding was obtained by self-administered questionnaires at the time of urine sampling. In practice, 17,468 cases were available, from which 12,869 cases were employed in the present analyses after exclusion of smokers, former or current patients of anemia or hypertension, and those with incomplete answers. Lactation burden was scored after coding of breast, mixed, and bottle feeding with 2, 1, and 0 for each child followed by summation for all children born to a mother. In order to exclude possible effect of aging, women were stratified by 5 years of age to randomly select equal numbers of cases and controls, followed by summation for all ages for comparison.

Results

The arithmetic mean age and the geometric mean Cd (as observed) were 49.7 years and 1.13 μg/l urine. The number of children was 0–7, and lactation burden score ranged from 0–12. Multiple regression analyses were conducted with age and either number of children or lactation burden scores as independent variables and Cd as a dependent variable. The results showed that age was an influential variable. Comparison after matching for age showed that having 1, 2, or 3 children or lactation burden score up to 2 were associated with a significant increase in Cd. Lactation burden score up to 2 was also associated with increased Cd in urine and such trend persisted up to the highest score of 5–12. The results of trend tests were generally in agreement with these observations. Further comparison after age-matching showed that women having 2 or 3 children but no lactation burden had higher Cd than those with no children. In contrast, Cd was not higher for those having 2 or 3 children with substantial lactation scores (i.e., 2–4 or 3–6) than for those with the same number of children without lactation burden.

Conclusions

Giving birth to 1–3 children was associated with an increase in urinary Cd, suggesting that child birth might be associated with elevation in Cd body burden. The effect of lactation is probably attributable to that of number of children. Further studies are necessary to examine whether the association is also observable in mothers who have 3 or more children.     

Consumption of a high β-glucan barley flour improves glucose control and fatty liver and increases muscle acylcarnitines in the Zucker diabetic fatty rat

Purpose

The soluble fiber β-glucan, a natural component of barley, has been shown to lower the postprandial glucose response and is thought to improve insulin resistance.

Methods

This study examined the effect of chronic consumption of the high β-glucan barley flour on glucose control, liver lipids and markers of muscle fatty acid oxidation in the Zucker diabetic fatty (ZDF) rat. Two groups of ZDF rats were fed diets containing either 6 % β-glucan in the form of barley flour or cellulose as a control for 6 weeks. A group of Zucker lean rats served as a negative control.

Results

The barley flour group had an increased small intestinal contents viscosity compared to the obese control group. After 6 weeks, the barley flour group had reduced glycated hemoglobin, lower relative kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Fasting plasma adiponectin levels increased in the barley flour group and were not different than the lean control group. ZDF rats on the barley flour diet had lower relative epididymal fat pad weights than the obese control and a greater food efficiency ratio. The barley flour group also had reduced liver weights and a decreased concentration of liver lipids. The barley flour group had significantly higher concentrations of muscle acylcarnitines, a metabolite generated during fatty acid oxidation.

Conclusion

These results show that chronic consumption of β-glucans can improve glucose control and decrease fatty liver in a model of diabetes with obesity.     

Comparison of free fructose and glucose to sucrose in the ability to cause fatty liver

Background

There is evidence that disaccharide sucrose produce a greater increase in serum fructose and triglycerides (TGs) than the effect produced by their equivalent monosaccharides, suggesting that long-term exposure to sucrose or fructose + glucose could potentially result in different effects.

Aim of the study

We studied the chronic effects of a combination of free fructose and glucose relative to sucrose on rat liver.

Methods

Rats were fed either a combination of 30% fructose and 30% glucose (FG) or 60% sucrose (S). Control rats were fed normal rat chow (C). All rats were pair fed and were followed for 4 months. After killing, blood chemistries and liver tissue were examined.

Results

Both FG-fed- and S-fed rats developed early features of metabolic syndrome when compared with C. In addition, both diets induced hepatic alterations, including variable increases in hepatic TG accumulation and fatty liver, an increase in uric acid content in the liver, as well as an increase in hepatic levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) measured in liver homogenates.

Conclusions

Diets containing 30% of fructose either as free fructose and glucose, or as sucrose, induce metabolic syndrome, intrahepatic accumulation of uric acid and TGs, increased MCP-1 and TNF-α as well as fatty liver in rats. It will be relevant to determine clinically whether pharmacological reduction in uric acid levels might have a therapeutic advantage in the treatment of non-alcoholic fatty liver disease.     

Consuming two additional serves of dairy food a day significantly improves energy and nutrient intakes in ambulatory aged care residents: A feasibility study

Objetives

Low-level aged-care residents are at risk of malnutrition. Oral supplements and fortified foods used to treat malnutrition in the elderly require special preparation and administration by staff. Therefore we aimed to determine if increasing dairy food intake in residents by two serves per day would improve energy and nutrient intakes and prevent malnutrition in residents.

Design

Prospective intervention study.

Setting

2 intervention and 2 control low-level aged-care facilities in Melbourne, Australia.

Participants

130 residents (n = 68 intervention, 78% female, mean age 86.5 years).

Intervention

This feasibility study was a 4-week intervention where menus were modified to include at least two additional serves of dairy food/day. Control facilities consumed from their regular menus.

Measurements

Mean macro- and micro-nutrient intakes before and after intervention and over the same time period in controls were recorded using observed intake (food served minus waste) and changes over time determined using paired t-tests. Comparison in proportion of residents meeting nutritional requirements was determined using Chi-square distribution test.

Results

Following intervention, daily increases in mean energy intake (900kJ, P<0.001), protein intake (+25g, P<0.0001), proportion of energy from protein (+4%, P<0.0001) and proportion of estimated energy requirements (EER) (+18%, P<0.0001) were observed, while proportion of energy from fat decreased (?3%, P<0.0001). In controls mean energy intake remained below the EER, and protein intake remained unchanged. Increases in mean daily micronutrient intakes were observed for numerous nutrients including calcium (+679mg, P<0.0001), vitamin D (+1.4μg, P<0.0001), phosphorus (+550mg, P<0.0001), and zinc (+2.8mg, P<0.0001), which remained unchanged in control residents. Calcium and zinc intakes achieved recommended intake levels on the higher dairy diet, but were below recommended levels in controls. Mean sodium intakes remained unchanged. During intervention a greater proportion of residents achieved the EER for energy and the RDI for protein and calcium compared to controls.

Conclusion

Two additional serves of dairy food can significantly improve nutrient intake in aged-care residents and its ease of provision makes it a viable option to potentially prevent malnutrition..     

Effect of ascorbic acid deficiency on catecholamine synthesis in adrenal glands of SMP30/GNL knockout mice

Purpose

The effect of an AA deficiency on catecholamine biosynthesis in adult mice in vivo is unknown. Therefore, we quantified catecholamine and the expression of catecholamine synthetic enzymes in the adrenal glands of senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice placed in an AA-deficient state.

Methods

At 30 days of age, mice were divided into the following 4 groups: AA (?) SMP30/GNL KO, AA (+) SMP30/GNL KO, AA (?) wild type (WT), and AA (+) WT. The AA (+) groups were given water containing 1.5 g/L AA, whereas the AA (?) groups received water without AA until the experiment ended. In addition, all mice were fed an AA-depleted diet. Catecholamine levels were measured by a liquid chromatographic method. Tyrosine hydroxylase, dopa decarboxylase, dopamine β-hydroxylase, and phenylethanolamine N-methyltransferase mRNA expression levels were measured with the quantitative real-time polymerase chain reaction (qPCR). Tyrosine hydroxylase and dopamine β-hydroxylase protein levels were quantified by Western blot analysis.

Results

In the adrenals of AA (?) SMP30/GNL KO mice, noradrenaline and adrenaline levels decreased significantly compared to other three groups of mice, although there were no significant differences in dopamine β-hydroxylase or phenylethanolamine N-methyltransferase mRNA content. Moreover, there was no significant difference in their dopamine β-hydroxylase protein levels. On the other hand, AA depletion did not affect dopamine levels in adrenal glands of mice.

Conclusion

An AA deficiency decreases the noradrenaline and adrenaline levels in adrenal glands of mice in vivo.     

Anti-anaemia efficacy of β-lactoglobulin hydrolysate-iron complex on iron-deficient anaemic rats

Purpose

The effects of orally administered β-lactoglobulin hydrolysate-iron complex (β-LGH-Fe) on haematological and biochemical parameters in anaemic rats were evaluated. Female weaning Sprague–Dawley rats were fed with iron-deficient diet to induce iron deficiency anaemia. After 6 weeks, the obtained anaemic rats were divided into five groups: iron deficiency control group (iron-deficient diet without β-LGH-Fe complex supplementation, IDC); three groups supplemented with different dosages of β-LGH-Fe complex (0.5 mg Fe/kg BW, iron-deficient diet with low β-LGH-Fe, IDLFe; 2.0 mg Fe/kg BW, iron-deficient diet with medium β-LGH-Fe, IDMF; 4.0 mg Fe/kg BW, iron-deficient diet with high β-LGH-Fe, IDHFe); and ferrous sulphate-supplemented group at a dosage of 2.0 mg Fe/kg BW.

Results

β-LGH-Fe complex could significantly improve hematocrit and haemoglobin decrease, and normalise the serum iron level, total iron-binding capacity and transferrin saturation of anaemic rats in a dose-dependent manner. Serum ferritin content and hepatic nonheme iron level were also increased. In addition, the antioxidant enzyme activities of superoxidase dismutase, catalase and glutathione peroxidase in both plasma and liver homogenate were improved. The production of malondialdehyde and pro-inflammatory cytokines (TNF-α and IL-6) decreased.

Conclusions

It suggests that β-LGH-Fe complex can ameliorate iron deficiency anaemia, which might make it a potential ingredient with anti-anaemia activity.     

Future outpatient health-care utilisation in an ageing population: projections up to the year 2020 based on the Study of Health in Pomerania (SHIP)

Aim

The population in the German federal state of Mecklenburg-West Pomerania is growing older. The resulting increase in the incidence of age-related diseases will lead to a higher demand for medical care although the population is declining. The aim of the study was to project the future outpatient health-care utilisation.

Subjects and methods

Representative data on health-care utilisation were derived from the Study of Health in Pomerania (SHIP). Participants (n?=?3,292, age 25–84 years) were asked whether they had consulted a physician in the past year and if so, the type of physician and the total number of visits. These data were combined with demographic forecasts for Mecklenburg-West Pomerania and its rural and urban districts up to the year 2020 to project the number of patients and their number of consultations with general practitioners and specialists in outpatient care.

Results

The projected number of annual consultations will increase in 2020 as compared to 2008 for urologists (+14.5 %), internists (+11.2 %), ophthalmologists (+7.7 %), neurologists (+6.0 %) and general practitioners (+5.8 %). In contrast, visits to gynaecologists will decrease until 2020 (?10.8 %). The predicted changes in the number of consultations show considerable heterogeneity between the districts.

Conclusion

Physicians who are consulted mainly by senior patients will face a higher number of consultations in 2020. Similar developments will probably occur in other German federal states and other industrialised countries in which demographic transition is already evident. These changes have to be considered in a rational planning of future medical-care provision.     

Maternal caffeine administration leads to adverse effects on adult mice offspring

Purpose

This study aimed to evaluate the role of caffeine chronic administration during gestation of C57BL/6 mice on cardiac remodeling and the expression of components of the renin-angiotensin system (RAS) in male offspring as adults.

Methods

Pregnant C57BL/6 female mice were divided into two groups (n = 10): Control group (C), dams were injected with the vehicle only (saline 0.9 % NaCl); Caffeine group (CF), dams received daily a subcutaneous injection of 20 mg/kg of caffeine/day (1 mg/mL saline). Pups had free access to standard chow since weaning to 3 months of age, when they were killed.

Results

CF group showed increased energy expenditure (+7 %) with consequent reduction in body mass (BM) gain (?18 %), increased blood pressure (+48 %), and higher heart rate (+10 %) than C group. The ratio between LV mass/BM was greater (+10 %), with bigger cardiomyocytes (+40 %), and reduced vascularization (?25 %) in CF group than in C group. In the LV, the expression of angiotensin-converting enzyme (+30 %), Angiotensin II (AngII) (+60 %), AngII receptor (ATR)-1 (+77 %) were higher, and the expression of ATR-2 was lower (?46 %; P < 0.05) in CF group than in C group. In the kidney, the expressions of renin (+128 %) and ATR-1 (+88 %) were higher in CF group than in C group.

Conclusions

Chronic administration of caffeine to pregnant dams led to persistent activation of local RAS in the kidney and heart of the offspring, which, in turn, leads to high BP and adverse cardiac remodeling. These findings highlight the urge to encourage pregnant women to avoid food or medicines containing caffeine.     

Long-term effect of altered nutrition induced by litter size manipulation and cross-fostering in suckling male rats on development of obesity risk and health complications

Objective

We investigated the long-term effect of pre-weaning nutrition on positive and/or adverse regulation of obesity risk and health complications in male Sprague–Dawley rats.

Design and subject

Two experimental models were used in the present work: (1) To induce postnatal over- or normal nutrition, the litter size was adjusted to 4 (small litters—SL) and to 10 pups (normal litters—NL) in the nest, (2) in suckling pups at day 10, we used cross-fostering to identify the effect of altered dietary environment on their future body fat regulation, food intake, blood pressure, and the duodenal and jejunal alkaline phosphatase activity. After weaning, these control (NL, SL) and cross-fostered (NL–SL, SL–NL) groups were exposed to standard laboratory diet.

Results

On day 50, the SL in comparison with NL rats became heavier and displayed enhanced adiposity accompanied by significantly increased systolic blood pressure (19 %) and duodenal (16 %) and jejunal (21 %) alkaline phosphatase (AP) activity. The impact of pre-weaning over-nutrition of NL–SL pups was associated with long-lasting positive effect on obesity. In contrast, SL–NL rats submitted until weaning to the opposite normalized feeding condition on day 50 showed significantly decreased fat deposition (21 %), systolic blood pressure (20 %), and AP activity in duodenum and jejunum (14 %).

Conclusions

These results contribute to a better understanding of how early-acquired dietary habits determine the attenuation or prevention of obesity development in later life and can provide some benefit for optimizing the future dietary strategies in young and adult obese individuals.     

Rapeseed and milk protein exhibit a similar overall nutritional value but marked difference in postprandial regional nitrogen utilization in rats

Background

Rapeseed is an emerging and promising source of dietary protein for human nutrition and health. We previously found that rapeseed protein displayed atypical nutritional properties in humans, characterized by low bioavailability and a high postprandial biological value. The objective of the present study was to investigate the metabolic fate of rapeseed protein isolate (RPI) and its effect on protein fractional synthesis rates (FSR) in various tissues when compared to a milk protein isolate (MPI).

Methods

Rats (n = 48) were given a RPI or MPI meal, either for the first time or after 2-week adaptation to a MPI or RPI-based diet. They were divided in two groups for measuring the fed-state tissue FSR 2 h after the meal (using a flooding dose of ¹³C-valine) and the dietary N postprandial distribution at 5 h (using ¹⁵N-labeled meals).

Results

RPI and MPI led to similar FSR and dietary nitrogen (N) losses (ileal and deamination losses of 4% and 12% of the meal, respectively). By contrast, the dietary N incorporation was significantly higher in the intestinal mucosa and liver (+36% and +16%, respectively) and lower in skin (-24%) after RPI than MPI.

Conclusions

Although RPI and MPI led to the same overall level of postprandial dietary N retention in rats (in line with our findings in humans), this global response conceals marked qualitative differences at the tissue level regarding dietary N accretion. The fact that FSR did not however differed between groups suggest a differential modulation of proteolysis after RPI or MPI ingestion, or other mechanisms that warrant further study.     

The effect of iron and zinc supplementation and its discontinuation on liver antioxidant status in rats fed deficient diets

Purpose

The aim was to investigate the effect of iron or combined iron/zinc supplementation on rat liver antioxidant status.

Methods

The 6-week male Wistar rats were examined in 3 stages: (1) 4-week adaptation to the diets (C—control AIN-93M diet, D—iron deficient and R—with 50 % reduction in all vitamin and mineral amounts); (2) 4-week supplementation with the same regimen enriched with tenfold more iron or iron/zinc; (3) 2-week post-supplementation period (the same diets as in the stage I).

Results

Combined iron/zinc supplementation similarly to iron supplementation alone significantly (p values ≤ 0.05) increased the iron content in the liver in D and R rats after stages II and III. Moreover, iron/zinc supplementation compared to iron supplementation alone significantly decreased the liver concentration of 8-isoprostane (after stage II in D and after stage III in R rats), protein carbonyl groups (only after stage III in R rats) and 8-hydroxy-2-deoxyguanosine (after stage II in R and after stage III in D and R rats). In rats fed R-type of diets after stage II hepatic superoxide dismutase (SOD) and catalase (CAT) activity, but not glutathione peroxidation activity and total antioxidant capacity, was lower in iron and iron/zinc supplemented than in non-supplemented rats, whereas after stage III in iron/zinc supplemented SOD was lower and CAT activity was higher in comparison with non-supplemented and iron supplemented rats.

Conclusions

The simultaneous iron/zinc supplementation can protect liver against peroxidative damage induced by high doses of iron during and after the intervention in rats fed iron-deficient diet and diet with reduced amounts of vitamins and minerals. The post-intervention observation is relevant because the effect may be delayed and visible only after this period.     

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.     

β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

Background

Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.

Methods

Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study.

Results

In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet.

Conclusions

These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.     

Anti-hyperglycemic and anti-hyperlipidemic effects of guava leaf extract

Background

The combination of oleoyl-estrone (OE) and a selective β₃-adrenergic agonist (B3A; CL316,243) treatment in rats results in a profound and rapid wasting of body reserves (lipid).

Methods

In the present study we investigated the effect of OE (oral gavage) and/or B3A (subcutaneous constant infusion) administration for 10 days to overweight male rats, compared with controls, on three distinct white adipose tissue (WAT) sites: subcutaneous inguinal, retroperitoneal and epididymal. Tissue weight, DNA (and, from these values cellularity), cAMP content and the expression of several key energy handling metabolism and control genes were analyzed and computed in relation to the whole site mass.

Results

Both OE and B3A significantly decreased WAT mass, with no loss of DNA (cell numbers). OE decreased and B3A increased cAMP. Gene expression patterns were markedly different for OE and B3A. OE tended to decrease expression of most genes studied, with no changes (versus controls) of lipolytic but decrease of lipogenic enzyme genes. The effects of B3A were widely different, with a generalized increase in the expression of most genes, including the adrenergic receptors, and, especially the uncoupling protein UCP1.

Discussion

OE and B3A, elicit widely different responses in WAT gene expression, end producing similar effects, such as shrinking of WAT, loss of fat, maintenance of cell numbers. OE acted essentially on the balance of lipolysis-lipogenesis and the blocking of the uptake of substrates; its decrease of synthesis favouring lipolysis. B3A induced a shotgun increase in the expression of most regulatory systems in the adipocyte, an effect that in the end favoured again the loss of lipid; this barely selective increase probably produces inefficiency, which coupled with the increase in UCP1 expression may help WAT to waste energy through thermogenesis.

Conclusions

There were considerable differences in the responses of the three WAT sites. OE in general lowered gene expression and stealthily induced a substrate imbalance. B3A increasing the expression of most genes enhanced energy waste through inefficiency rather than through specific pathway activation. There was not a synergistic effect between OE and B3A in WAT, but their combined action increased WAT energy waste.     

Feeding oxidized fat during pregnancy up-regulates expression of PPARα-responsive genes in the liver of rat fetuses

Background

Feeding oxidized fats causes activation of peroxisome proliferator-activated receptor α (PPARα) in the liver of rats. However, whether feeding oxidized fat during pregnancy also results in activation of PPARα in fetal liver is unknown. Thus, this study aimed to explore whether feeding oxidized fat during pregnancy causes a PPARα response in fetal liver. Two experiments with pregnant rats which were administered three different diets (control; oxidized fat; clofibrate as positive control) in a controlled feeding regimen during either late pregnancy (first experiment) or whole pregnancy (second experiment) were performed.

Results

In both experiments pregnant rats treated with oxidized fat or clofibrate had higher relative mRNA concentrations of the PPARα-responsive genes acyl-CoA oxidase (ACO), cytochrome P₄₅₀ 4A1 (CYP4A1), L-type carnitin-palmitoyl transferase I (L-CPT I), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in the liver than control rats (P < 0.05). In addition, in both experiments fetuses of the oxidized fat group and the clofibrate group also had markedly higher relative mRNA concentrations of ACO, CYP4A1, CPT I, MCAD, and LCAD in the liver than those of the control group (P < 0.05), whereas the relative mRNA concentrations of PPARα, SREBP-1c, and FAS did not differ between treatment groups. In the second experiment treatment with oxidized fat also reduced triacylglycerol concentrations in the livers of pregnant rats and fetuses (P < 0.05).

Conclusion

The present study demonstrates for the first time that components of oxidized fat with PPARα activating potential are able to induce a PPARα response in the liver of fetuses. Moreover, the present study shows that feeding oxidized fat during whole pregnancy, but not during late pregnancy, lowers triacylglycerol concentrations in fetal livers.