Dietary regulation of catabolic disposal of 4-hydroxynonenal analogs in rat liver

Our previous work in perfused rat livers has demonstrated that 4-hydroxynonenal (HNE) is catabolized predominantly via β oxidation. Therefore, we hypothesized that perturbations in β oxidation, such as diet-altered fatty acid oxidation activity, could lead to changes in HNE levels. To test our hypothesis, we (i) developed a simple and sensitive GC/MS method combined with mass isotopomer analysis to measure HNE and HNE analogs, 4-oxononenal (ONE) and 1,4-dihydroxynonene (DHN), and (ii) investigated the effects of four diets (standard, low-fat, ketogenic, and high-fat mix) on HNE, ONE, and DHN concentrations in rat livers. Our results showed that livers from rats fed the ketogenic diet or high-fat mix diet had high ω-6 polyunsaturated fatty acid concentrations and markers of oxidative stress. However, high concentrations of HNE (1.6 ± 0.5 nmol/g) and ONE (0.9 ± 0.2 nmol/g) were found only in livers from rats fed the high-fat mix diet. Livers from rats fed the ketogenic diet had low HNE (0.8 ± 0.1 nmol/g) and ONE (0.4 ± 0.07 nmol/g), similar to rats fed the standard diet. A possible explanation is that the predominant pathway of HNE catabolism (i.e., β oxidation) is activated in the liver by the ketogenic diet. This is consistent with a 10-fold decrease in malonyl-CoA in livers from rats fed a ketogenic diet compared to a standard diet. The accelerated catabolism of HNE lowers HNE and HNE analog concentrations in livers from rats fed the ketogenic diet. On the other hand, rats fed the high-fat mix diet had high rates of lipid synthesis and low rates of fatty acid oxidation, resulting in the slowing down of the catabolic disposal of HNE and HNE analogs. Thus, decreased HNE catabolism from a high-fat mix diet induces high concentrations of HNE and HNE analogs. The results of this work suggest a potential causal relationship to metabolic syndrome induced by Western diets (i.e., high-fat mix), as well as the effects of a ketogenic diet on the catabolism of lipid peroxidation products in liver.     

Upregulation of hepatic autophagy under nutritional ketosis

Many of the metabolic effects evoked by the ketogenic diet mimic the actions of fasting and the benefits of the ketogenic diet are often attributed to these similarities. Since fasting is a potent autophagy inductor in vivo and in vitro it has been hypothesized that the ketogenic diet may upregulate autophagy. The aim of the present study was to provide a comprehensive evaluation of the influence of the ketogenic diet on the hepatic autophagy. C57BL/6N male mice were fed with two different ketogenic chows composed of fat of either animal or plant origin for 4 weeks. To gain some insight into the time frame for the induction of autophagy on the ketogenic diet, we performed a short-term experiment in which animals were fed with ketogenic diets for only 24 or 48 h. The results showed that autophagy is upregulated in the livers of animals fed with the ketogenic diet. Moreover, the size of the observed effect was likely dependent on the diet composition. Subsequently, the markers of regulatory pathways that may link ketogenic diet action to autophagy were measured, i.e., the activity of mTORC1, activation of AMPK, and the levels of SIRT1, p53, and FOXO3. Overall, observed treatment-specific effects including the upregulation of SIRT1 and downregulation of FOXO3 and p53. Finally, a GC/MS analysis of the fatty acid composition of animals’ livers and the chows was performed in order to obtain an idea about the presence of specific compounds that may shape the effects of ketogenic diets on autophagy.     

Effects of dietary polyamines and clofibrate on metabolism of polyamines in the rat

The activities of catalase, polyamine oxidase, diamine oxidase, ornithine decarboxylase, and peroxisomal β-oxidation were assayed in homogenates from liver and small intestinal mucosa of rats which had been fed either a diet very low in polyamines or a diet containing five times the levels of dietary polyamines (putrescine, spermine, and spermidine) found in a standard rat diet. In rats fed the high polyamine diet, hepatic activities of catalase and polyamine oxidase were significantly decreased. Levels of the other activities were unchanged, except that intestinal ornithine decarboxylase was decreased. In rats treated simultaneously with clofibrate, the high polyamine diet restored activities of catalase, ornithine decarboxylase, and polyamine oxidase back to levels found in rats fed the low polyamine diet. The expected increase in activity of peroxisomal β-oxidation was observed, although this was somewhat diminished in rats fed the high polyamine diet. Intestinal diamine oxidase activity was stimulated by clofibrate, particularly in rats fed the high polyamine diet. For the duration of the experiment (20 days), levels of putrescine, spermine, and spermidine in blood remained remarkably constant irrespective of treatment, suggesting that polyamine homeostasis is essentially independent of dietary supply of polyamines. It is suggested that intestinal absorption/metabolism of polyamines is of significance in this respect. Treatment with clofibrate appeared to alter polyamine homeostasis.     

Effects of dietary lactose and purified diet on intestinal microflora of rats

In the rats fed on lactose-containing purified diet (PDL), bifidobacteria remarkably increased in number in both the jejunum and cecum as compared with those fed on control diet (PD) or conventional diet (NMF). Besides, lactobacilli, streptococci, staphylococci, and Escherichia coli increased in number in the jejuna and/or ceca of rats fed on PDL as compared with those fed on PD. The incidence and numbers of Lactobacillus species were remarkably different between the rats fed on PDL and those on any of the other diets. Indole-producing Bacteroides spp. were rarely isolated from the PDL-fed rats. The cecum was markedly enlarged in the PDL rats and reduced in the PD rats as compared with that in the NMF animals.     

Ketogenic Diet Increases Glutathione Peroxidase Activity in Rat Hippocampus

Ketogenic diets have been used in the treatment of refractory childhood epilepsy for almost 80 years; however, we know little about the underlying biochemical basis of their action. In this study, we evaluate oxidative stress in different brain regions from Wistar rats fed a ketogenic diet. Cerebral cortex appears to have not been affected by this diet, and cerebellum presented a decrease in antioxidant capacity measured by a luminol oxidation assay without changes in antioxidant enzyme activities—glutathione peroxidase, catalase, and superoxide dismutase. In the hippocampus, however, we observed an increase in antioxidant activity accompanied by an increase of glutathione peroxidase (about 4 times) and no changes in lipoperoxidation levels. We suggest that the higher activity of this enzyme induced by ketogenic diet in hippocampus might contribute to protect this structure from neurodegenerative sequelae of convulsive disorders.     

Physiological Considerations of Lipid Storage and Utilization

Normally, rats and mice eat chow-type rations. When fed sucha ration, body fat usually ranges between 11 and 18%. If a semi-purifieddiet high in fat is fed instead of the chow-type ration, somestrains of rats and mice respond by accumulating abnormal amountsof weight and fat. Their bodies now contain as much as 40% fatand fat depots are enlarged. Rats which respond to a high fatdiet with excessive weight and fat gain consume more kilocaloriesin the same time interval and are more efficient in energy utilizationthan rats of the same strain which consume a grain diet. Forthese rats, if medium-chain triglycerides are substituted forthe long-chain triglycerides in the high fat diet, there isa depression in food intake, accretion of body weight and fatas well as energy utilization. Blood makes up 3.5 to 5.1% of the fat organ weight. The lowervalue represents the quantity present in adipose tissue of obeserats while the higher value is for "normal-weight" rats. Thetriglyceride content of perirenal and epididymal fat depotsis around 90%. On the other hand, the triglyceride content ofinguinal fat tissue ranges from 56 to 80% and is affected bystrain, age and diet. If diets are high in fat, the proportionaldistribution of fatty acids in the adipose tissue reflects theproportional distribution in dietary fat, except when medium-chaintriglycerides are fed.     

Effect of clofibrate feeding on some lipogenic enzyme activities induced by high carbohydrate diet

Clofibrate administration by stomach tube or intraperitoneally for 3 successive days to rats fed standard diet or starved for 72 hr caused about 2-fold increase of malic enzyme activity in the liver and adipose tissue. The drug administered by stomach tube (but not intraperitoneally) to the rats fed fat free-high carbohydrate diet significantly blocked the inducing effect of the diet on malic enzyme activity in both tissues. Clofibrate blocked the induction by fat free-high carbohydrate diet of hexose monophosphate shunt dehydrogenases and ATP-citrate lyase in the liver. The amount of fat free-high carbohydrate diet consumed by rats received clofibrate by stomach tube was much less than by untreated animals. It is concluded therefore that the significant decrease of food consumption by rats receiving clofibrate by stomach tube is responsible for the inhibitory effect of the drug on some lipogenic enzymes activity induced by fat free-high carbohydrate diet.     

Ketogenic Diet Improves Core Symptoms of Autism in BTBR Mice

Autism spectrum disorders share three core symptoms: impaired sociability, repetitive behaviors and communication deficits. Incidence is rising, and current treatments are inadequate. Seizures are a common comorbidity, and since the 1920’s a high-fat, low-carbohydrate ketogenic diet has been used to treat epilepsy. Evidence suggests the ketogenic diet and analogous metabolic approaches may benefit diverse neurological disorders. Here we show that a ketogenic diet improves autistic behaviors in the BTBR mouse. Juvenile BTBR mice were fed standard or ketogenic diet for three weeks and tested for sociability, self-directed repetitive behavior, and communication. In separate experiments, spontaneous intrahippocampal EEGs and tests of seizure susceptibility (6 Hz corneal stimulation, flurothyl, {"type":"entrez-protein","attrs":{"text":"SKF83822","term_id":"1156217297"}}SKF83822, pentylenetetrazole) were compared between BTBR and control (C57Bl/6) mice. Ketogenic diet-fed BTBR mice showed increased sociability in a three-chamber test, decreased self-directed repetitive behavior, and improved social communication of a food preference. Although seizures are a common comorbidity with autism, BTBR mice fed a standard diet exhibit neither spontaneous seizures nor abnormal EEG, and have increased seizure susceptibility in just one of four tests. Thus, behavioral improvements are dissociable from any antiseizure effect. Our results suggest that a ketogenic diet improves multiple autistic behaviors in the BTBR mouse model. Therefore, ketogenic diets or analogous metabolic strategies may offer novel opportunities to improve core behavioral symptoms of autism spectrum disorders.     

Preventive effects of dehydroepiandrosterone acetate on the fatty liver induced by orotic acid in male rats.

Preventive effects of dehydroepiandrosteone acetate (DHEA-A) and clofibrate (positive control substance) on the fatty liver induced by orotic acid (OA) were examined on the male Sprague-Dawley rats fed a high sucrose based diet containing 1% OA and this diet further mixed with 0.5% DHEA-A or 0.5% clofibrate for 2 weeks. Numerous lipid droplets were observed in the hepatocytes of the rats treated with OA alone, but not in those treated with DHEA-A or clofibrate. In comparison to the group with OA alone, the DHEA-A or clofibrate treated rats showed a larger relative liver weight (to body weight) which was accompanied by increased peroxisomes in the hepatocytes. These results indicate that DHEA-A, as well as clofibrate, may prevent OA-induced fatty liver.     

The effect of diet and 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) on microsomal hydroxylating enzymes and on sensitivity of rats to carbon tetrachloride poisoning

1. Protein-depleted rats are resistant to the lethal effects of carbon tetrachloride. The LD₅₀ is 6·4ml./kg. in stock rats and 14·7ml./kg. in rats fed on protein-free diets. 2. Protein-depleted rats are resistant to carbon tetrachloride in its effect on the liver as judged by histology, accumulation of liver water, and plasma enzyme and bilirubin measurement. 3. The protection is present after feeding rats on a no-protein diet for 4 days. It is present after feeding rats on a 3%-casein diet, and partly found after feeding rats on a 6%-casein diet. 4. The activities of the microsomal enzymes that demethylate Pyramidon and hydroxylate benzopyrene in the liver fall by over 80% in rats fed on the no-protein diet for 4 days or more, or in rats fed on a 3%-casein diet. A 50% fall is found in rats fed on a 6%-casein diet. 5. A single dose of DDT or three doses of phenobarbitone cause increased microsomal enzyme activity in protein-depleted rats. 6. The animals are then sensitive to the lethal and liver-damaging effects of carbon tetrachloride. 7. DDT dosage also leads to increased sensitivity to carbon tetrachloride in rats fed on stock diets. 8. These findings support the hypothesis that carbon tetrachloride is metabolized by microsomal enzymes to form the true toxic compound.     

Organic aciduria in rats made resistant to hypoglycin toxicity by pretreatment with clofibrate.

1. The lethal, hypoglycaemic and hypothermic effects of hypoglycin in fasted rats are prevented if the rats had been fed on a diet containing clofibrate (0.5% w/w). 2. Injection of hypoglycin into fasted rats maintained on a standard diet caused severe prostration, hypothermia and a massive dicarboxylic aciduria [Tanaka (1972) J. Biol. Chem. 247, 7465-7478]. 3. Rats maintained on a diet containing clofibrate appeared normal after injection of hypoglycin, but had a marked dicarboxylic aciduria which was less than that induced in rats on a normal diet. 4. After administration of hypoglycin, butyryl-CoA and decanoyl-CoA, but not palmitoyl-CoA, dehydrogenase activities were strongly inhibited (80-95%) in the livers of animals on a standard diet. 5. Clofibrate feeding decreased the inhibition of these dehydrogenases to about 40-60%. 6. It was concluded that although clofibrate protects against the toxic effects of hypoglycin, some enzyme inhibitions as indicated by dicarboxylic aciduria are only partly prevented.     

Hypocholesterolemic mechanism of Chlorella: Chlorella and its indigestible fraction enhance hepatic cholesterol catabolism through up-regulation of cholesterol 7alpha-hydroxylase in rats

Chlorella powder (CP) has a hypocholesterolemic effect and high bile acid-binding capacity; however, its effects on hepatic cholesterol metabolism are still unclear. In the present study, male Wistar rats were divided into four groups and fed a high sucrose + 10% lard diet (H), an H + 10% CP diet (H+CP), an H + 0.5% cholesterol + 0.25% sodium cholate diet (C), or a C + 10% CP diet (C+CP) for 2 weeks. CP decreased serum and liver cholesterol levels significantly in rats fed C-based diets, but did not affect these parameters in rats fed H-based diets. CP increased the hepatic mRNA level and activity of cholesterol 7alpha-hydroxylase (CYP7A1). CP increased hepatic HMG-CoA reductase (HMGR) activity in the rats fed H-based diets, but not in rats fed C-based diets. CP did not affect hepatic mRNA levels of sterol 27-hydroxylase, HMGR, low-density lipoprotein (LDL) receptor, scavenger receptor class B1, ATP-binding cassette (ABC) A1, ABCG5, or ABCB11. Furthermore, the effect of a 3.08% Chlorella indigestible fraction (CIF, corresponding to 10% CP) on hepatic cholesterol metabolism was determined using the same animal models. CIF also decreased serum and liver cholesterol levels significantly in rats fed C-based diets. CIF increased hepatic CYP7A1 mRNA levels. These results suggest that the hypocholesterolemic effect of CP involves enhancement of cholesterol catabolism through up-regulation of hepatic CYP7A1 expression and that CIF contributes to the hypocholesterolemic effect.     

The effect of three hypolipidemic drugs on catalase activity and peroxisomal and mitochondrial palmitate oxidation in rat cardiac and skeletal muscle

Catalase activity and peroxisomal and mitochondrial palmitate oxidation have been investigated in cardiac and skeletal muscle from rats fed clofibrate, ciprofibrate or nafenopin in an unrefined diet for different periods of time. Nafenopin was also added to either a high carbohydrate (70% of kilocalories from glucose) or high fat (70% of kilocalories from lard) diet and fed to rats for either 1 or 3 weeks. Catalase activity was elevated in all muscles from rats fed the hypolipidemic drugs. The response of catalase activity in muscle to clofibrate was dose-dependent. The response time of catalase activity was different in individual muscles. Peroxisomal palmitate oxidation was elevated in the heart and soleus muscle from rats fed nafenopin in either the high-carbohydrate or the high-fat diet. There was no change in peroxisomal palmitate oxidation in psoas or extensor digitorum longus muscle from rats fed the drugs. Mitochondrial palmitate oxidation was only slightly increased by nafenopin in the heart and soleus muscles after 3 weeks of nafenopin feeding. The results suggest that the cardiac muscle, like the liver, responds to hypolipidemic drug treatment with an increase in peroxisomal fat oxidation. The skeletal muscle response is less specific and that tissue may not contribute to the hypolipidemic effect of the drugs. The findings also suggest that these drugs do not induce peroxisome proliferation in skeletal muscle.     

Effects of Exposure to Dietary Chromium on Tissue Mineral Contents in Rats Fed Diets with Fiber

This study evaluated the effects of diets with fiber (cellulose and/or pectin) supplemented with chromium(III) on homeostasis of selected minerals in femurs, thigh muscles, livers, and kidneys of rats. For 6 weeks, male rats were fed experimental diets: a fiber-free diet (FF), a diet containing 5 % cellulose (CEL), 5 % pectin (PEC), or 2.5 % cellulose and 2.5 % pectin (CEL?+?PEC). These diets had 2.53 or 0.164 mg Cr/kg diet. The tissue levels of Ca, Mg, Zn, Fe, and Cr were determined by using atomic absorption spectrometry. Supplementing diets with Cr resulted in significantly higher Cr levels in the femurs of rats fed the CEL diet and significantly higher Cr and Fe levels in the rats fed the CEL?+?PEC diet compared to the rats fed FF diet. Muscle Ca content was significantly lower in the rats fed the CEL?+?PEC?+?Cr diet compared to the rats fed FF?+?Cr diet. The rats consuming the PEC?+?Cr diet had the highest liver Cr content. The highest kidney Zn content was observed in the rats fed diets containing Cr and one type of fiber. These results indicate that diets containing chromium at elevated dose and fiber have a significant effect on the mineral balance in rat tissues.     

Tryptophan Metabolism of Rats Fed on an Amino Acid Diet Devoid of One Branched Chain Amino Acid

In an attempt to study on metabolic changes in rats fed on an amino acid diet devoid of one branched chain amino acid and of niacin, rats were force-fed a leucine-free, isoleucine-free, valine-free or complete amino acid diet for 3 or 4 days and killed 3 hr after the feeding on day 4 or 5 to observe the body weight changes, the urinary nitrogen and N¹-methylnicotinamide (MNA), and liver tryptophanpyrrolase (TPase) and tyrosine-α-keto-glutarate transaminase (TKase) activities.

The excretion of the urinary nitrogen and MNA, TPase and TKase activities, and fat content of livers of rats force-fed these amino acid deficient diets were higher than those fed the complete amino acid diet. It was further confirmed in the present study that changes in TPase activity of rats given diets devoid of one essential amino acid were in the same direction with changes in urinary MNA which was observed in the previous studies on rats given threonine-free, tryptophan-free, methionine-free, lysine-free and complete amino acid diets. However, such metabolic changes in rats fed the leucine-free diet were not so remarkable, compared with those of rats fed the other amino acid deficient diets.     

Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein

Low-carbohydrate/high-fat diets (LC-HFDs) in rodent models have been implicated with both weight loss and as a therapeutic approach to treat neurological diseases. LC-HFDs are known to induce ketosis; however, systematic studies analyzing the impact of the macronutrient composition on ketosis induction and weight loss success are lacking. Male Wistar rats were pair-fed for 4 wk either a standard chow diet or one of three different LC-HFDs, which only differed in the relative abundance of fat and protein (percentages of fat/protein in dry matter: LC-75/10; LC-65/20; LC-55/30). We subsequently measured body composition by nuclear magnetic resonance (NMR), analyzed blood chemistry and urine acetone content, evaluated gene expression changes of key ketogenic and gluconeogenic genes, and measured energy expenditure (EE) and locomotor activity (LA) during the first 4 days and after 3 wk on the respective diets. Compared with chow, rats fed with LC-75/10, LC-65/20, and LC-55/30 gained significantly less body weight. Reductions in body weight were mainly due to lower lean body mass and paralleled by significantly increased fat mass. Levels of β-hydroxybutyate were significantly elevated feeding LC-75/10 and LC-65/20 but decreased in parallel to reductions in dietary fat. Acetone was about 16-fold higher with LC-75/10 only (P < 0.001). In contrast, rats fed with LC-55/30 were not ketotic. Serum fibroblast growth factor-21, hepatic mRNA expression of hydroxymethylglutaryl-CoA-lyase, peroxisome proliferator-activated receptor-γ coactivator-1α, and peroxisome proliferator-activated receptor-γ coactivator-1β were increased with LC-75/10 only. Expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was downregulated by 50-70% in LC-HF groups. Furthermore, EE and LA were significantly decreased in all groups fed with LC-HFDs after 3 wk on the diets. In rats, the absence of dietary carbohydrates per se does not induce ketosis. LC-HFDs must be high in fat, but also low in protein contents to be clearly ketogenic. Independent of the macronutrient composition, LC-HFD-induced weight loss is not due to increased EE and LA.     

Roles of nuclear receptors in the up-regulation of hepatic cholesterol 7alpha-hydroxylase by cholestyramine in rats

Nuclear receptors are involved in regulating the expression of cholesterol 7alpha-hydroxylase (CYP7A1), however, their roles in the up-regulation of CYP7A1 by cholestyramine (CSR) are still unclear. In the present study, male Wistar rats were divided into four groups and fed [high sucrose + 10% lard diet] (H), [H + 3% CSR diet] (H + CSR), [H + 0.5% cholesterol + 0.25% sodium cholate diet] (C), or [C + 3% CSR diet] (C + CSR) for 2 weeks. Cholestyramine decreased serum and liver cholesterol levels significantly in rats fed C-based diets, but had no effect on these parameters in rats fed H-based diets. Cholestyramine raised hepatic levels of CYP7A1 mRNA and activity in both groups. The gene expression of hepatic ATP-binding cassettes A1 and G5, regulated by liver X receptor (LXR), were unchanged and down-regulated by cholestyramine, respectively. The mRNA levels of the hepatic ATP-binding cassette B11 and short heterodimer partner (SHP), regulated by farnesoid X receptor (FXR), were not changed by cholestyramine. C-based diets, which contained cholesterol and cholic acid, increased SHP mRNA levels compared to H-based diets. Consequently, in rats fed the C+CSR diet, hepatic FXR was activated by dietary bile acids, but the hepatic CYP7A1 mRNA level was increased 16-fold compared to that in rats fed an H diet. These results suggest that cholestyramine up-regulates the expression of CYP7A1 independently via LXR- or FXR-mediated pathways in rats.     

Mineral supplementation of white wheat flour is necessary to maintain adequate mineral status and bone characteristics in rats

This experiment was designed to compare the effect of ingestion of a wheat flours on mineral status and bone characteristics in rats. White flour was tested either without further mineral supplementation or with Mg, Fe, Zn and Cu supplementation. The flour diets were compared to a control purified diet. Four groups of 10 male Wistar rats each were fed one of the experimental diets for 6 wk and mineral status and tissue retention as well as bone characteristics were determined. As expected, mineral intake, except for calcium, was significantly lesser in rats fed the white flour diet than in the other groups. The rats fed the white flour diet had the lowest food intake, weight gain, fecal excretion and intestinal fermentation. The most important result was that Mg and Fe status were drastically lower in rats fed the white flour diet than in those fed whole flour or control diets. The status of these both elements were significantly improved by the mineral supplementation of white flour. There were no major significant differences between mineral-supplemented white flour and whole flour groups in mineral status. Furthermore, bone mineral densities (total, metaphyseal and diphyseal) were significantly lower in rats fed white flour diet compared to the other diet groups, while no significant difference was observed between the mineral-supplemented white flour, whole flour or control diet groups. In conclusion, the present work shows clearly the importance of mineral-supplementation of white wheat flour to sustain an adequate intake of minerals. Our results indicate also that the whole wheat flour did not negatively alter mineral bioavailability, in comparison to mineral supplemented white flour. Clinical studies are still needed to confirm these rat results in human.     

Zinc deficiency and the activities of lipoprotein lipase in plasma and tissues of rats force-fed diets with coconut oil or fish oil

The present study was performed to investigate the effect of zinc deficiency on the activities of lipoprotein lipase in postheparin serum and tissues of rats fed diets containing either coconut oil or fish oil as dietary fat, using a bifactorial experimental design. To ensure an adequate food intake, all the rats were force-fed by gastric tube. Experimental diets contained either 0.8 mg zinc/kg (zinc-deficient diets) or 40 mg zinc/kg (zinc-adequate diets). The effects of zinc deficiency on the activities of lipoprotein lipase in postheparin serum and postprandial triglyceride concentrations and distribution of apolipoproteins in serum lipoproteins depended on the type of dietary fat. Zinc-deficient rats fed the coconut oil diet exhibited a reduced activity of lipoprotein lipase in postheparin serum and adipose tissue, markedly increased concentrations of triglycerides in serum, and a markedly reduced content of apolipoprotein C in triglyceride-rich lipoproteins and high density lipoproteins compared with zinc-adequate rats fed coconut oil. By contrast, zinc-deficient rats fed the fish oil diet did not exhibit reduced activities of lipoprotein lipase in postheparin serum and adipose tissue and increased concentrations of serum lipids compared with zinc-adequate rats fed the fish oil diet. This study suggests that a reduced activity of lipoprotein lipase might contribute to increased postprandial concentrations of serum triglycerides observed in zinc-deficient animals. However, it also demonstrates that the effects of zinc deficiency on lipoprotein metabolism are influenced by dietary fatty acids.     

Phytase supplementation increases bone mineral density,lean body mass and voluntary physical activity in rats fed a low-zinc diet

Phytic acid forms insoluble complexes with nutritionally essential minerals, including zinc (Zn). Animal studies show that addition of microbial phytase (P) to low-Zn diets improves Zn status and bone strength. The present study determined the effects of phytase supplementation on bone mineral density (BMD), body composition and voluntary running activity of male rats fed a high phytic acid, low-Zn diet. In a factorial design, rats were assigned to ZnLO (5 mg/kg diet), ZnLO+P (ZnLO diet with 1500 U phytase/kg) or ZnAD (30 mg/kg diet) groups and were divided into voluntary exercise (EX) or sedentary (SED) groups, for 9 weeks. SED rats were significantly heavier from the second week, and no catch-up growth occurred in EX rats. Feed intakes were not different between groups throughout the study. ZnLO animals had decreased food efficiency ratios compared to both phytase-supplemented (ZnLO+P) and Zn-adequate (ZnAD) animals (P<.01 compared to ZnLO). The ZnLO+P and ZnAD rats ran 56–75 km more total distance than ZnLO rats (P<.05), with the ZnLO+P rats running more kilometers per week than the ZnLO rats by Week 6. In vivo DEXA analyses indicate that rats fed phytase-supplemented diets had higher lean body mass (LBM) than those fed ZnLO diets; and that rats fed the Zn-adequate diets had the highest LBM. Body fat (%) was significantly lower in EX rats and was both Zn- and phytase insensitive. Rats fed phytase-supplemented diets had higher bone mineral content (BMC), bone area (BA) and BMD than rats fed ZnLO diets; and in rats fed ZnAD diets these indices were the highest. The dietary effects on BMC, BA and BMD were independent of activity level.We conclude that consuming supplemental dietary phytase or dietary Zn additively enhances Zn status to increase BMD, LBM and voluntary physical activity in rats fed a low-Zn diet. While the findings confirm that bone health is vulnerable to disruption by moderate Zn deficiency in rats, this new data suggests that if dietary Zn is limiting, supplemental phytase may have beneficial effects on LBM and performance activity.