Effects of lipoprotein lipase gene variations, a high-carbohydrate low-fat diet, and gender on serum lipid profiles in healthy Chinese Han youth

A high-carbohydrate low-fat (HC/LF) diet and lipoprotein lipase gene (LPL) Ser447Stop and Hind III polymorphisms have separately been found to be associated with triacylglycerol (TG) and high density lipoprotein cholesterol (HDL-C). This study sought to test the effects of LPL polymorphisms and an HC/LF diet on the serum lipid profile of Chinese with a lower incidence of coronary artery disease (CAD) consuming a diet with less fat and more carbohydrates. Fifty-six healthy subjects (22.89 ± 1.80 years) were given a control diet of 30.1% fat and 54.1% carbohydrates for 7 days, followed by an HC/LF diet of 13.8% fat and 70.1% carbohydrate for 6 days; there were no changes in the fatty acid composition or restrictions on total energy. Serum lipid profiles at baseline, before and after the HC/LF diet, and LPL polymorphisms were analyzed. After 6 days of the HC/LF diet, TG and the homeostasis model assessment of insulin resistance (HOMAIR) index were found to increase only in females with S447S. No decrease in HDL-C was noted. In subjects with Hind III polymorphism, increased TG was found in all females but not in males. Increased HDL-C, together with apolipoprotein (apo) AI, was found in male H- carriers but not in males with H+/H+ and females. In conclusion, LPL Ser447Stop and Hind III polymorphisms modified the effects of an HC/LF diet on the serum lipid profiles of a young Chinese population in different ways. Effective strategies for dietary interventions targeted at younger populations should take into account the interplay between genetic polymorphisms, diet, and gender.

Effects of dietary fat and conjugated linoleic acid on plasma metabolite concentrations and metabolic responses to homeostatic signals in pigs

Sixteen female cross-bred (Large White × Landrace) pigs (initial weight 65 kg) with venous catheters were randomly allocated to four treatment groups in a 2×2 factorial design. The respective factors were dietary fat (25 or 100 g/kg) and dietary conjugated linoleic acid (CLA; 0 or 10 g CLA-55/kg). Pigs were fed every 3 h (close to ad libitum digestible energy intake) for 8 d and were bled frequently. Plasma glucose and non-esterified fatty acid (NEFA) responses to insulin and adrenaline challenges were determined on day 8. Plasma concentrations of NEFA were significantly increased (10·5 and 5·4 % for low- and high-fat diets respectively, P=0·015) throughout the experiment, suggesting that there was a possible increase in fat mobilisation. The increase in lipolysis, an indicator of ß-adrenergic stimulated lipolysis, was also evident in the NEFA response to adrenaline. However, the increase in plasma triacylglycerol (11·0 and 7·1 % for low- and high-fat diets respectively, P=0·008) indicated that CLA could have reduced fat accretion via decreased adipose tissue triacylglycerol synthesis from preformed fatty acids, possibly through reduced lipoprotein lipase activity. Plasma glucose, the primary substrate for de novo lipid synthesis, and plasma insulin levels were unaffected by dietary CLA suggesting that de novo lipid synthesis was largely unaffected (P=0·24 and P=0·30 respectively). In addition, the dietary CLA had no effect upon the ability of insulin to stimulate glucose removal.

Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE^-/-) and compared with wild-type littermates. Compared with wild-type littermates, ACE^-/- mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE^-/- mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE^-/- mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excrete in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE^-/- mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.

Impact of obesity and leptin treatment on adipocyte gene expression in Psammomys obesus

We examined the effects of leptin treatment on the expression of key genes in adipocyte metabolism in Psammomys obesus (P. obesus), a polygenic rodent model of obesity. Lean and obese P. obesus were given three daily intraperitoneal injections of either saline or leptin (total of 45 mg/kg per day) for 7 days. In lean animals, leptin treatment led to reductions in food intake, body weight and fat mass. Pair-fed animals matched for the reduction in food intake of the lean leptin-treated animals demonstrated similar reductions in body weight and fat mass. In obese P. obesus, leptin treatment failed to have any effect on body weight or body fat mass, indicating leptin resistance. Lipoprotein lipase, hormone-sensitive lipase and peroxisome proliferator activated receptor gamma 2 mRNA levels were significantly reduced in lean leptin-treated animals, whereas pair-fed animals were similar to lean controls. Uncoupling protein 2 and glycerol phosphate acyltransferase were also reduced in the lean leptin-treated animals, but not significantly so. Obese animals did not show any gene expression changes after leptin treatment. In conclusion, high circulating concentrations of leptin in lean P. obesus resulted in decreased gene expression of a number of key lipid enzymes, independent of changes in food intake, body weight and fat mass. These effects of leptin were not found in obese P. obesus.

Lipid abundance in zebrafish embryos is regulated by complementary actions of the endocannabinoid system and retinoic acid pathway

The endocannabinoid system (ECS) and retinoic acid (RA) signaling have been associated with influencing lipid metabolism. We hypothesized that modulation of these pathways could modify lipid abundance in developing vertebrates and that these pathways could have a combinatorial effect on lipid levels. Zebrafish embryos were exposed to chemical treatments altering the activity of the ECS and RA pathway. Embryos were stained with the neutral lipid dye Oil-Red-O (ORO) and underwent whole-mount in situ hybridization. Mouse 3T3-L1 fibroblasts were differentiated under exposure to RA modulating chemicals and subsequently stained with ORO and analyzed for gene expression by qRT-PCR. ECS activation and RA exposure increased lipid abundance and the expression of lipoprotein lipase. Additionally, RA treatment increased expression of CCAAT/enhancer binding protein alpha. Both ECS receptors and RA receptor subtypes were separately involved in modulating lipid abundance. Finally, increased ECS or RA activity ameliorated the reduced lipid abundance caused by peroxisome proliferator-activated receptor gamma (PPARγ) inhibition. Therefore, the ECS and RA pathway influence lipid abundance in zebrafish embryos and have an additive effect when treated simultaneously. Furthermore, we demonstrated that these pathways act downstream or independently of PPARγ to influence lipid levels. Our study shows for the first time that the RA and ECS pathways have additive function in lipid abundance during vertebrate development.

Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles. Male Sprague Dawley rats were treated with simvastatin (60 or 80 mg·kg(-1)·day(-1)) or vehicle control via oral gavage for 14 days. In the absence of overt muscle damage, simvastatin treatment induced an increase in atrogin-1, MuRF1 and myostatin mRNA expression; however, these were not associated with changes in peroxisome proliferator gamma co-activator 1 alpha (PGC-1α) protein or markers of mitochondrial content. Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK α-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles. Furthermore, simvastatin induced a decrease in β-hydroxyacyl CoA dehydrogenase (β-HAD) activity only in FT muscles. These findings suggest that the statin-induced activation of muscle atrophy genes occurs independent of changes in PGC-1α protein and mitochondrial content. Moreover, muscle-specific increases in NOS expression and possibly NO production, and decreases in fatty acid oxidation, could contribute to the previously reported development of overt statin-induced muscle damage in FT muscles.

Zinc deficiency and its inherited disorders - A review

Zinc is an essential trace element required by all living organisms because of its critical roles both as a structural component of proteins and as a cofactor in enzyme catalysis. The importance of zinc in human metabolism is illustrated by the effects of zinc deficiency, which include a diminished immune response, reduced healing and neurological disorders. Furthermore, nutritional zinc deficiency can be fatal in newborn or growing animals. While zinc deficiency is commonly caused by dietary factors, several inherited defects of zinc deficiency have been identified. Acrodermatitis enteropathica is the most commonly described inherited condition found in humans. In several of the few cases that have been reported, this disorder is associated with mutations in the hZIP4 gene, a member of the SLC39 family, whose members encode membranebound putative zinc transporters. Mutations in other members of this family or in different genes may account for other cases of acrodermatitis in which defects in hZIP4 have not been detected. Another inherited form of zinc deficiency occurs in the lethal milk mouse, where a mutation in ZnT4 gene, a member of the SLC30 family of transmembrane proteins results in impaired secretion of zinc into milk from the mammary gland. A similar disorder to the lethal milk mouse occurs in humans. In the few cases studied, no changes in ZnT4 orthologue, hZnT4, were detected. This, and the presence of several minor phenotypic differences between the zinc deficiency in humans and mice, suggests that the human condition is caused by defects in genes that are yet to be identified. Taking into account the fact that there are no definitive tests for zinc deficiency and that this disorder can go undiagnosed, plus the recent identification of multiple members of the SCL30 and SLC39, it is likely that mutations in other genes may underlie additional inherited disorders of zinc deficiency.

Impetus to explore: approaching operational deficiency optimistically

‘Impetus to explore’ is studied through post-lesson video-stimulated student interviews. This impetus focuses ‘spontaneous’ decisions to explore unfamiliar mathematics. Uncertainty, quests for elegance and curiosity have been found to contribute to this impetus. This study identified other contributing factors: inability to undertake the teacher’s task, ‘optimistic explanatory style’ (Seligman, 1995), and identifying relevant complexities (Williams, 2002). Explanatory style affects how a person perceives successes and failures. Enactment of optimism in this study illuminated its role in creating an impetus to explore. Re-conceptualising ‘operational deficiency’ (Chen & Siegler, 2000) to include absence of resources to undertake a task illuminated a task design feature that can increase exploration.

Structural deficiency or cultural racism: the educational and social experiences of Arab-Australian youth

This paper discusses the cultural, attitudinal and structural factors that impact upon the social experiences and educational achievements of Arabic-speaking background (ASB) students in three Melbourne secondary schools with high levels of cultural and linguistic diversity. The paper makes the case for and then outlines a multidimensional approach to multicultural education to better integrate ASB students and their families into the schooling environment. Key strategies developed and tested include a model of school-community partnership, online and interactive teacher support material (TSM) as well as on-going teacher professional development workshops on reflexive approaches to cultural diversity and intercultural tension.

Effect of dietary omega-3 fatty acid deficiency on heart rate variability in hooded rats

Introduction: Recent reports in adult humans suggest that heart rate variability is modulated by the concentration of omega-3 polyunsaturated fatty acids (PUFA) contained in blood cell membranes. Material and methods: Hurst analysis of ECG data was conducted on 12 male adult hooded (Long-Evans) rats, representing the 3rd generation to be fed diets that were either deficient in, or supplemented with, omega-3 PUFA. ECG data were obtained from surface electrodes and 4000 beats were analyzed for each animal. Results: Dietary manipulation, despite leading to large changes in tissue omega- 3 PUFA levels, did not significantly affect the complexity of heart rate dynamics, with Hurst exponent (H) values of 0.15±0.02 and 0.12±0.03, for animals fed omega- 3 fatty acid-adequate and -deficient diets, respectively. Mean heart rate was also unaffected by the diets. A power calculation revealed that about one hundred animals per group would have been required to avoid a type II error. Conclusions: According to this model of dietary PUFA manipulation, omega-3 fatty acids are unlikely to exert a large effect on the autonomic functions that control heart rate variability. Prospective studies into the effect of omega-3 fatty acids on HRV should consider the need for large sample size as estimated by the results contained in this report.

Adiponectin in umbillcal cord blood is inversely related to low-density lipoprotein cholesteril but not ethnicity

Context: Adiponectin is a recognized protective risk marker for cardiovascular disease in adults and is associated with an optimal lipid profile. The role of adiponectin at birth is not well understood, and its relationship with the neonatal lipid profile is unknown. Because ethnic disparities in cardiovascular risk have been attributed to low adiponectin and its associated low high-density lipoprotein cholesterol (HDL-C), investigation at birth may help determine the etiology of these risk patterns.

Objective: Our objective was to investigate the relationship between neonatal adiponectin and lipid profile at birth in two ethnic groups in cord blood.

Design, Setting, and Participants: Seventy-four healthy mothers and their newborns of South Asian and White European origin were studied in this cross-sectional study at St. Mary’s Hospital, Manchester, United Kingdom.

Main Outcome Measures: Serum adiponectin, total cholesterol, HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were measured in umbilical venous blood at birth and in maternal blood collected at 28 wk gestation.

Results: Cord adiponectin was significantly inversely associated with cord LDL-C (r = –0.32; P = 0.005) but not HDL-C. In a multiple regression analysis, cord LDL-C remained the most significant association of cord adiponectin (ß = –0.13; P < 0.001). We did not find any significant ethnic differences in cord adiponectin or lipids with the exception of triglycerides, which were significantly lower in South Asian newborns (P < 0.05).

Conclusion: This is the first report of an inverse relationship between cord adiponectin and LDL-C at birth. In contrast to adult studies, we found no significant association between adiponectin and HDL-C in cord blood. Our results and the strong independent association between adiponectin and HDL-C observed in adult studies suggest a role for adiponectin in lipid metabolism. Ethnic differences in adiponectin may arise after birth.

Increased blood pressure later in life may be associated with perinatal n-3 fatty acid deficiency

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n−3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n−3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control. This study investigated the importance of perinatal n−3 PUFA supply in the control of blood pressure in adult Sprague-Dawley rats. Pregnant rat dams were fed semisynthetic diets that were either deficient in (DEF) or supplemented with (CON) n−3 PUFA. Offspring were fed the same diets as their mothers until 9 wk; then, half of the rats from each group were crossed over to the opposite diet, creating four groups, i.e., CON-CON; CON-DEF; DEF-DEF, DEF-CON. Mean arterial blood pressures (MAP) were measured directly, at 33 wk of age, by cannulation of the femoral artery. The phospholipid fatty acid profile of the hypothalamic region was determined by capillary gas-liquid chromatography. The tissue phospholipid fatty acid profile reflected the diet that the rats were consuming at the time of testing. Both groups receiving DEF after 9 wk of age (i.e., DEF-DEF and CON-DEF) had similar profiles with a reduction in DHA levels of 30%, compared with rats receiving CON (i.e., CON-CON and DEF-CON). DEF-DEF rats had significantly raised MAP compared with all other groups, with differences as great as 17 mm Hg. DEF-CON rats had raised MAP compared with CON-CON rats, and DEF-DEF rats had higher MAP than CON-DEF rats, despite the fact that their respective fatty acid profiles were not different. These findings indicate that inadequate levels of DHA in the perinatal period are associated with altered blood pressure control in later life. The way in which these long-term effects are produced remains to be elucidated.

Does perinatal ω-3 polyunsaturated fatty acid deficiency increase appetite signaling?

Objective: To investigate the effect of maternal dietary ω-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling.
Research Methods and Procedures: Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) ω-3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2-deoxyglucose injection), or by blocking β-oxidation of fatty acids (by β-mercaptoacetate injection).
Results: DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9-fold) demonstrated following administration of 2-deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2-deoxyglucose but not to β-mercaptoacetate.
Discussion: These findings indicate that supply of ω-3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of ω-3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.

Dietary protein level interacts with ω-3 polyunsaturated fatty acid deficiency to induce hypertension

Background : Dietary ω-3 fatty acid deficiency can lead to hypertension in later life; however, hypertension is affected by numerous other dietary factors. We examined the effect of altering the dietary protein level on blood pressure in animals deficient or sufficient in ω-3 fatty acids.

Methods : Female rats were placed on one of four experimental diets 1 week prior to mating. Diets were either deficient (10% safflower oil; DEF) or sufficient (7% safflower oil, 3% flaxseed oil; SUF) in ω-3 fatty acids and contained 20 or 30% casein (DEF20, SUF20, DEF30, SUF30). Offspring were maintained on the maternal diet for the duration of the experiment. At 12, 18, 24, and 30 weeks, blood pressure was assessed by tail cuff plethysmography.

Results : At both 12 and 18 weeks of age, no differences in blood pressure were observed based on diet, however, by 24 weeks hypertension was evident in DEF30 animals; there were no blood pressure differences between the other groups. This hypertension in DEF30 group was increased at 30 weeks, with systolic, diastolic, and mean arterial pressure all elevated.

Conclusions : These results indicate that the hypertension previously attributed to ω-3 fatty acid deficiency is dependent on additional dietary factors, including protein content. Furthermore, this study is the first to plot the establishment of ω-3 fatty acid deficiency hypertension over time.