Nutrition & Metabolism - Latest Articles

Effects of combined maternal administration with alpha-ketoglutarate (AKG) and beta-hydroxy-beta- methylbutyrate (HMB) on prenatal programming of skeletal properties in the offspring

Marcin Tatara — 2012-05-11T00:00:00Z

Background: Nutritional manipulations during fetal growth may induce long-term metabolic effects inpostnatal life. The aim of the study was to test whether combined treatment of pregnant sowswith alpha-ketoglutarate and beta-hydroxy-beta-methylbutyrate induces additive long-term effectson skeletal system properties in the offspring. Methods: The study was performed on 290 pigs obtained from 24 sows divided into 4 equal groups andsubjected to experimental treatment during two weeks before delivery. The first groupconsisted of control sows, while the second group received alpha-ketoglutarate. The thirdgroup was treated with beta-hydroxy-beta-methylbutyrate and the fourth group underwentcombined administration of alpha-ketoglutarate and beta-hydroxy-beta-methylbutyrate. Pigletsobtained from sows were reared until slaughter age to perform morphometric, densitometricand mechanical analyses of femur. Serum evaluations of growth hormone, insulin-likegrowth factor-1, bone-specific alkaline phosphatase and osteocalcin were performed innewborns and 90-day old piglets; additionally, plasma amino acid concentration wasmeasured in newborns. Results: Maternal treatment with alpha-ketoglutarate and beta-hydroxy-beta-methylbutyrate significantlyreduced fattening time and increased birth body weight, daily body weight gain, bone weight,volumetric bone mineral density, geometrical parameters and mechanical endurance offemur. These effects were associated with increased serum concentrations of growthhormone, insulin-like growth factor-1, bone-specific alkaline phosphatase and osteocalcin.Furthermore, alpha-ketoglutarate and beta-hydroxy-beta-methylbutyrate administered solely or incombination significantly increased plasma level of 19 amino acids. Conclusions: Hormonal and amino acid evaluations in pigs indicate additive effects of AKG and HMB onsystemic growth and development; however, determination of bone properties has not shownsuch phenomenon.

Substrate utilization during submaximal exercise in children with a severely obese parent

Audrey Eaves — 2012-05-09T00:00:00Z

Background: We have reported a reduction in fatty acid oxidation (FAO) at the whole-body level and inskeletal muscle in severely obese (BMI [greater than or equal to] 40 kg/m2) individuals; this defect is retained in cellculture suggesting an inherent component. The purpose of the current study was to determineif an impairment in whole-body fatty acid oxidation (FAO) was also evident in children witha severely obese parent. Methods: Substrate utilization during submaximal exercise (cycle ergometer) was determined inchildren ages 8-12 y with a severely obese parent (OP, n = 13) or two lean/non-obese (BMIrange of 18 to 28 kg/m2) parents (LP, n = 13). A subgroup of subjects (n = 3/group)performed 4 weeks of exercise training with substrate utilization measured after theintervention. Results: The children did not differ in age (LP vs. OP, respectively) (10.7 +/- 0.5 vs. 10.2 +/- 0.5 y), BMIpercentile (65.3 +/- 5.2 vs. 75.9 +/- 7), Tanner Stage (1.4 +/- 0.2 vs. 1.5 +/- 0.2), VO2peak (40.3 +/-2.7 vs. 35.6 +/- 2.6 ml/kg/min) or physical activity levels (accelerometer). At the same absoluteworkload of 15 W (~38% VO2peak), RER was significantly (P [less than or equal to] 0.05) lower in LP vs. OP(0.83 +/- 0.02 vs. 0.87 +/- 0.01) which was reflected in a reduced reliance on FAO for energyproduction in the OP group (58.6 +/- 5.1 vs. 43.1 +/- 4.0% of energy needs during exercise fromFAO). At a higher exercise intensity (~65% VO2peak) there were no differences in substrateutilization between LP and OP. After exercise training RER tended to decrease (P = 0.06) atthe 15 W workload, suggesting an increased reliance on FAO regardless of group. Conclusions: These findings suggest that the decrement in FAO with severe obesity has an inherentcomponent that may be overcome with exercise training.

Meju, unsalted soybeans fermented with Bacillus subtilis and Aspergilus oryzae, potentiates insulinotropic actions and improves hepatic insulin sensitivity in diabetic rats

Hye Jeong Yang — 2012-05-02T00:00:00Z

Background: Although soybeans have the ability to attenuate insulin resistance, it is insufficient to alleviatetype 2 diabetic symptoms and different types of fermented soybeans may have even betteranti-diabetic effects. Meju, unsalted fermented soybeans exhibited better insulin sensitizingand insulinotropic actions than unfermented cooked soybeans (CSB). We investigatedwhether meju fermented in the traditional (TMS) manner for 60 days and meju fermented inthe standardized (MMS) method inoculating Bacillus subtilis and Aspergillus oryzae for 6days modulated insulin resistance, insulin secretion, and pancreatic beta-cell growth andsurvival in 90% pancreatectomized (Px) diabetic rats, a moderate and non-obese type 2diabetic animal model. Methods: Diabetic rats were divided into 3 groups: 1) TMS (n = 20), 2) MMS (n = 20) or 3) casein(control; n = 20). Rats were provided with a high fat diet (40 energy % fat) containingassigned 10% meju for 8 weeks. At the end of experiment insulin resistance and insulinsecretion capacity were measured by euglycemic hyperinsulinemic clamp and byhyperglycemic clamp, respectively. Additionally, beta-cell mass and islet morphohometry weredetermined by immunohistochemistry and insulin signaling in the liver was measured bywestern blot. Results: TMS and MMS increased isoflavonoid aglycones much more than CSB. CSB andTMS/MMS improved glucose tolerance in diabetic rats but the mechanism was differentbetween treatments (P < 0.05). CSB enhanced peripheral insulin sensitivity including hepaticinsulin sensitivity better than the control but TMS and MMS enhanced only hepatic insulinsensitivity through activating insulin signaling in diabetic rats (P < 0.05). However, TMS andMMS, but not CSB, potentiated glucose-stimulated insulin secretion and beta-cell mass (P <0.05). MMS had better insulinotropic actions than the control (P < 0.05). Conclusions: The anti-diabetic action of MMS, especially when fermented with Bacillus subtilis andAspergillus oryzae, was superior to CSB by increasing isoflavonoid aglycones and smallpeptides with regard to type 2 diabetic rats.

Exploring metabolic dysfunction in chronic kidney disease

Adrian Slee — 2012-04-26T00:00:00Z

Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure andend-stage renal disease (ESRD) is a serious medical condition associated with increasedmorbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associatedwith multiple physiological and metabolic disturbances, including hypertension, dyslipidemiaand the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal,inflammatory, and nutritional-metabolic factors may play key roles in CKD development andpathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and 6,tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin,increased C-reactive protein, and perturbations in normal anabolic hormone responses withreduced growth hormone-insulin-like growth factor-1 axis activity. Others includehyperactivation of the renin-angiotensin aldosterone system (RAAS), with angiotensin II andaldosterone implicated in hypertension and the promotion of insulin resistance, andsubsequent pharmacological blockade shown to improve blood pressure, metabolic controland offer reno-protective effects. Abnormal adipocytokine levels including leptin andadiponectin may further promote the insulin resistant, and proinflammatory state in CKD.Ghrelin may be also implicated and controversial studies suggest activities may be reduced inhuman CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin Dstatus has also been associated with patient outcome and CVD risk and may indicate a rolefor supplementation. Glucocorticoid activities traditionally known for their involvement inthe pathogenesis of a number of disease states are increased and may be implicated in CKDassociatedhypertension, insulin resistance, diabetes risk and cachexia, both directly andindirectly through effects on other systems including activation of the mineralcorticoidreceptor. Insight into the multiple factors altered in CKD may provide useful information ondisease pathogenesis, clinical assessment and treatment rationale such as potentialpharmacological, nutritional and exercise therapies.

The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis

Penelope Main — 2012-04-24T00:00:00Z

Background: Glutathione has a wide range of functions; it is an endogenous anti-oxidant and plays a key role in the maintenance of intracellular redox balance and detoxification of xenobiotics. Several studies have indicated that children with autism spectrum disorders may have altered glutathione metabolism which could play a key role in the condition. Methods: A systematic literature review and meta-analysis was conducted of studies examining metabolites, interventions and/or genes of the glutathione metabolism pathways i.e. the gamma-glutamyl cycle and trans-sulphuration pathway in autism spectrum disorders. Results: Thirty nine studies were included in the review comprising an in vitro study, thirty two metabolite and/or co-factor studies, six intervention studies and six studies with genetic data as well as eight studies examining enzyme activity. Conclusions: The review found evidence for the involvement of the gamma-glutamyl cycle and trans-sulphuration pathway in autistic disorder is sufficiently consistent, particularly with respect to the glutathione redox ratio, to warrant further investigation to determine the significance in relation to clinical outcomes. Large, well designed intervention studies that link metabolites, cofactors and genes of the gamma-glutamyl cycle and trans-sulphuration pathway with objective behavioural outcomes in children with autism spectrum disorders are required. Future risk factor analysis should include consideration of multiple nutritional status and metabolite biomarkers of pathways linked with the gamma-glutamyl cycle and the interaction of genotype in relation to these factors.

Docosahexaenoic acid ameliorates palmitate-induced lipid accumulation and inflammation through repressing NLRC4 inflammasome activation in HepG2 cells

Xiaoqin Luo — 2012-04-19T00:00:00Z

Background: N-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA; 22:6n-3), has clinicalsignificance in the prevention and reversal of nonalcoholic steatohepatitis (NASH). However,the precious mechanism underlying remains unclear. The inflammasome, a multiproteincomplex formed by NOD-like receptor (NLR) family members, has been recently shown tobe activated in NASH and promote the cleavage of the pro-inflammatory cytokines to theirmaturation forms. Methods: HepG2 cells were exposed to different dose of PA for 24 h with or without the preincubationof 50 muM DHA for another 24 h and then lipid deposition was assessed with Oil red Ostaining and intracellular triglyceride (TG) determination. Secretory levels of inflammatorycytokines and Caspase-1 activity were determined by ELISA assays. Gene expression andprotein levels were determined by quantitative RCR and western blotting, respectively. Results: Palmitate (PA) dose-dependently increased lipid accumulation, TG content and induced thesecretion of interleukin-1beta (IL-1beta), IL-18, TNF-alpha and MCP-1 from HepG2 cells.Preincubation with DHA significantly alleviated PA-induced lipid accumulation andinflammatory agents. DHA was also found to attenuate PA-induced NOD-like receptorprotein 4 (NLRC4) mRNA expression. Furthermore, PA induced caspase-1 activation in adose-dependent manner, resulting in exacerbating of procaspase-1 and pro-IL-1beta processing.Knockdown of NLRC4 partially abrogated PA-induced caspase-1 activation and IL-1betamaturation and completely abolished these events in the presence of DHA. Conclusions: Our findings indicate DHA attenuates PA-induced lipid accumulation and inflammationthrough suppressing NLRC4 inflammasome activation, caspase-1 activation and IL-1betacleavage.

Effects of regularly consuming dietary fibre rich soluble cocoa products on bowel habits in healthy subjects: a free-living, two-stage, randomized, crossover, single-blind intervention

Beatriz Sarria — 2012-04-18T00:00:00Z

Background: Dietary fibre is both preventive and therapeutic for bowel functional diseases. Soluble cocoa products are good sources of dietary fibre that may be supplemented with this dietary component. This study assessed the effects of regularly consuming two soluble cocoa products (A and B) with different non-starch polysaccharides levels (NSP, 15.1 and 22.0 % w/w, respectively) on bowel habits using subjective intestinal function and symptom questionnaires, a daily diary and a faecal marker in healthy individuals. Methods: A free-living, two-stage, randomized, crossover, single-blind intervention was carried out in 44 healthy men and women, between 18-55 y old, who had not taken dietary supplements,laxatives, or antibiotics six months before the start of the study. In the four-week-long intervention stages, separated by a three-week-wash-out stage, two servings of A and B, that provided 2.26 vs. 6.60 g/day of NSP respectively, were taken. In each stage, volunteers' diet was recorded using a 72-h food intake report. Results: Regularly consuming cocoa A and B increased fibre intake, although only cocoa B significantly increased fibre intake (p < 0.001) with respect to the non-cocoa stage. No changes in body weight were observed in either of the 4 week interventions. With cocoa product B, the number of daily bowel movements increased (p = 0.002), the frequency of having a bowel movement once a day increased (p = 0.009), the time to have a bowel movement was lower (p = 0.016) as well as the feeling of constipation (p = 0.046) without inducing adverse gastrointestinal symptoms, only flatulence increased (p = 0.019). Conclusions: Regular consumption of the cocoa products increases dietary fibre intake to recommended levels and product B improves bowel habits. The use of both objective and subjective assessments to evaluate the effects of food on bowel habits is recommended.

Chronic inflammatory diseases are stimulated by current lifestyle: how diet, stress levels and medication prevent our body from recovering

Margarethe Bosma-den Boer — 2012-04-17T00:00:00Z

Serhan and colleagues introduced the term "Resoleomics" in 1996 as the process of inflammation resolution. The major discovery of Serhan's work is that onset to conclusion of an inflammation is a controlled process of the immune system (IS) and not simply the consequence of an extinguished or "exhausted" immune reaction. Resoleomics can be considered as the evolutionary mechanism of restoring homeostatic balances after injury, inflammation and infection. Under normal circumstances, Resoleomics should be able to conclude inflammatory responses. Considering the modern pandemic increase of chronic medical and psychiatric illnesses involving chronic inflammation, it has become apparent that Resoleomics is not fulfilling its potential resolving capacity. We suggest that recent drastic changes in lifestyle, including diet and psycho-emotional stress, are responsible for inflammation and for disturbances in Resoleomics. In addition, current interventions, like chronic use of anti-inflammatory medication, suppress Resoleomics. These new lifestyle factors, including the use of medication, should be considered health hazards, as they are capable of long-term or chronic activation of the central stress axes. The IS is designed to produce solutions for fast, intensive hazards, not to cope with long-term, chronic stimulation. The never-ending stress factors of recent lifestyle changes have pushed the IS and the central stress system into a constant state of activity, leading to chronically unresolved inflammation and increased vulnerability for chronic disease. Our hypothesis is that modern diet, increased psycho-emotional stress and chronic use of anti-inflammatory medication disrupt the natural process of inflammation resolution ie Resoleomics.

Does dietary inulin affect biological activity of a grapefruit flavonoid-rich extract?

Adam Jurgonski — 2012-04-11T00:00:00Z

Background: The aim of the study was to verify that the concomitant presence of grapefruit flavonoid extract with inulin in a Western-type diet may provide synergistic effects to the hindgut metabolism, as well as blood lipid and mineral profiles. Methods: Forty male Wistar rats were distributed into 4 groups and fed for 28 days with diets rich in fat, cholesterol and protein. A two-way repeated measures ANOVA was applied to assess the effects of inulin (v. sucrose, 5% of the diet), the addition of dietary grapefruit flavonoid extract (diets without or with 0.3% of an extract from hard parts of grapefruit) and the interaction between these two dietary factors. Results: When compared to the control sucrose-containing diet, the diet enriched with inulin led to typical changes within the caecum, the main part of hindgut fermentation in rats, such as acidification of the digesta, support of bifidobacteria growth and increase of propionate and butyrate production. The dietary grapefruit flavonoid extract without inulin increased the bulk and pH value of caecal digesta, whereas short-chain fatty acid concentration and the bifidobacteria population were lowered compared to the extract-free diets. Simultaneous dietary addition of both tested components decreased slightly the pH value and increased somewhat the bifidobacteria number and the propionate concentration, however to the level observed with the control sucrose-containing diet. With regard to blood lipids, dietary grapefruit flavonoid extract decreased the triglyceride concentration regardless of the dietary carbohydrate type. Conclusion: Inulin does not provide any additional benefit to the blood lipid profile caused by the dietary application of grapefruit flavonoid extract and it does not counteract clearly detrimental effects of the extract in the hindgut. Adding grapefruit extract to the diet must be performed with caution due to possible adverse hindgut responses with overdoses.

Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-kappaB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats

Mustafa Yavuz Selcuk — 2012-04-08T00:00:00Z

Background: Diabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney. Methods: Male Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis. Results: The increased NF-κβ p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (P < 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (P < 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (P < 0.05) in diabetic rats. Conclusion: Our result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κβ p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.