Nutrition & Metabolism - Latest Articles

The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men

Karin Slivkoff-Clark — 2012-02-07T00:00:00Z

Background: Visceral obesity and insulin resistance are associated with a postprandial accumulation of atherogenic chylomicron remnants that is difficult to modulate with lipid-lowering therapies. Dietary fish oil and exercise are cardioprotective interventions that can significantly modify the metabolism of TAG-rich lipoproteins. In this study, we investigated whether chronic exercise and fish oil act in combination to affect chylomicron metabolism in obese men with moderate insulin resistance. Methods: The single blind study tested the effect of fish oil, exercise and the combined treatments on fasting and postprandial chylomicron metabolism. Twenty nine men with metabolic syndrome were randomly assigned to take fish oil or placebo for four weeks, before undertaking an additional 12 week walking program. At baseline and at the end of each treatment, subjects were tested for concentrations of fasting apo B48, plasma lipids and insulin. Postprandial apo B48 and TAG kinetics were also determined following ingestion of a fat enriched meal. Results: Combining fish oil and exercise resulted in a significant reduction in the fasting apo B48 concentration, concomitant with attenuation of the fasting TAG concentration and postprandial TAGIAUC response (P < 0.05). Fish oil by itself reduced the postprandial TAG response (P < 0.05) but not postprandial apo B48 kinetics. Individual treatments of fish oil and exercise did not correspond with improvements in fasting plasma TAG apo B48. Conclusion: Fish oil was shown to independently improve plasma TAG homeostasis but did not resolve hyper-chylomicronaemia. Instead, combining fish oil with chronic exercise reduced the plasma concentration of pro-atherogenic chylomicron remnants; in addition it reduced the fasting and postprandial TAG response in viscerally obese insulin resistant subjects.

Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type

Mette Kristensen — 2012-02-03T00:00:00Z

Background: Dietary fibers have been proposed to play a role in cardiovascular risk as well as body weight management. Flaxseeds are a good source of dietary fibers, and a large proportion of these are water-soluble viscous fibers.MethodHere, we examine the effect of flaxseed dietary fibers in different food matrices on blood lipids and fecal excretion of fat and energy in a double-blind randomized crossover study with 17 subjects. Three different 7-d diets were tested: a low-fiber control diet (Control), a diet with flaxseed fiber drink (3/day) (Flax drink), and a diet with flaxseed fiber bread (3/day) (Flax bread). Total fat and energy excretion was measured in feces, blood samples were collected before and after each period, and appetite sensation registered 3 times daily before main meals. Results: Compared to control, Flax drink lowered fasting total-cholesterol and LDL-cholesterol by 12 and 15%, respectively, (p<0.01), whereas Flax bread only produced a reduction of 7 and 9%, respectively (p<0.05). Fecal fat and energy excretion increased by 50 and 23% with Flax drink consumption compared to control (p<0.05), but only fecal fat excretion was increased with Flax bread compared to control (p<0.05). Conclusion: Both Flax drink and Flax bread resulted in decreased plasma total and LDL-cholesterol and increased fat excretion, but the food matrix and/or processing may be of importance. Viscous flaxseed dietary fibers may be a useful tool for lowering blood cholesterol and potentially play a role in energy balance.Trial registration: The study was registered in the clinicaltrials.gov database: NCT00953004.

Phenylketonuria: nutritional advances and challenges

Marcello Giovannini — 2012-02-03T00:00:00Z

Despite the appearance of new treatment, dietary approach remains the mainstay of PKU therapy. The nutritional management has become complex to optimize PKU patients' growth, development and diet compliance. This paper review critically new advances and challenges that have recently focused attention on potential relevant of LCPUFA supplementation, progress in protein substitutes and new protein sources, large neutral amino acids and sapropterin. Given the functional effects, DHA is conditionally essential substrates that should be supplied with PKU diet in infancy but even beyond. An European Commission Programme is going on to establish quantitative DHA requirements in this population. Improvements in the palatability, presentation, convenience and nutritional composition of protein substitutes have helped to improve long-term compliance with PKU diet, although it can be expected for further improvement in this area. Glycomacropeptide, a new protein source, may help to support dietary compliance of PKU subject but further studies are needed to evaluate this metabolic and nutritional issues. The PKU diet is difficult to maintain in adolescence and adult life. Treatment with large neutral amino acids or sapropterin in selected cases can be helpful. However, more studies are necessary to investigate the potential role, dose, and composition of large neutral amino acids in PKU treatment and to show long-term efficacy and tolerance. Ideally treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment, but clinical protocol evaluating adjustment of PKU diet and sapropterin dosage are needed.In conclusion PKU diet and the new existing treatments, that need to be optimized, may be a complete and combined strategy possibly positive impacting on the psychological, social, and neurocognitive life of PKU patients.

D-Lactate Altered Mitochondrial Energy Production in Rat Brain and Heart but not Liver

Binbing Ling — 2012-02-01T00:00:00Z

Background: Substantially elevated blood D-lactate (DLA) concentrations are associated with neurocardiac toxicity in humans and animals. The neurological symptoms are similar to inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that DLA interferes with mitochondrial utilization of L-lactate and pyruvate in brain and heart. Methods: Respiration rates in rat brain, heart and liver mitochondria were measured using DLA, LLA and pyruvate independently and in combination. Results: In brain mitochondria, state 3 respiration was 53% and 75% lower with DLA as substrate when compared with LLA and pyruvate, respectively (p<0.05). Similarly in heart mitochondria, state 3 respiration was 39% and 86% lower with DLA as substrate when compared with LLA or pyruvate, respectively (p<0.05). However, state 3 respiration rates were similar between DLA, LLA and pyruvate in liver mitochondria. Combined incubation of DLA with LLA or pyruvate markedly impaired state 3 respiration rates in brain and heart mitochondria (p<0.05) but not in liver mitochondria. DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase activities were similar across all three tissues. An LDH inhibitor blocked state 3 respiration with LLA as substrate in all three tissues. A monocarboxylate transporter inhibitor blocked respiration with all three substrates. Conclusions: DLA was a poor respiratory substrate in brain and heart mitochondria and inhibited LLA and pyruvate usage in these tissues. Further studies are warranted to evaluate whether these findings support, in part, the possible neurological and cardiac toxicity caused by high DLA levels.

Quality protein intake is inversely associated with abdominal fat

Jeremy Loenneke — 2012-01-27T00:00:00Z

Dietary protein intake and specifically the quality of the protein in the diet has become an area of recent interest. This study determined the relationship between the amount of quality protein, carbohydrate, and dietary fat consumed and the amount of times the ~10g essential amino acid (EAA) threshold was reached at a meal, with percent central abdominal fat (CAF). Quality protein was defined as the ratio of EAA to total dietary protein. Quality protein consumed in a 24-hour period and the amount of times reaching the EAA threshold per day was inversely related to percent CAF, but not for carbohydrate or dietary fat. In conclusion, moderate to strong correlations between variables indicate that quality and distribution of protein may play an important role in regulating CAF, which is a strong independent marker for disease and mortality.

High prevalence of gastroesophageal reflux symptoms in type 2 diabetics with hypoadiponectinemia and metabolic syndrome

Ayumu Hirata — 2012-01-25T00:00:00Z

Background: The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide. Abdominal obesity or visceral fat accumulation rather than simple obesity is associated with GERD. Previous reports demonstrated the association between GERD and type 2 diabetes mellitus (T2DM). Signification of visceral fat accumulation and adiponectin in T2DM patients with GERD remains unclear. The present study investigated the relationships between GERD symptoms, visceral fat accumulation and adiponectin in subjects with T2DM.FindingsThe study (ADMIT study) subjects were 66 Japanese T2DM outpatients, who answered the questionnaire regarding GERD symptoms in Frequency Scale for the Symptoms of GERD (FSSG), and were measured visceral fat area by bioelectrical impedance analysis. Patients with FSSG scores of more than 8 were considered as positive. The prevalence of FSSG score >8 and average FSSG score in T2DM subjects with the metabolic syndrome (Mets) were significantly higher compared to those without Mets. The prevalence of FSSG score 8 and average FSSG score in T2DM subjects with low levels of serum adiponectin were significantly higher compared to those with high levels of serum adiponectin. Moreover, the combination of Mets and hypoadiponectinemia had a multiplicative effect on GERD symptom score (p=0.047). Conclusions: Our study showed that the coexistence of MetS and low levels of serum adiponectin was associated with the higher prevalence of FSSG score >8 and the higher scores of GERD symptom in subjects with T2DM.Trial Registration: UMIN 000002271.

A high calcium diet containing nonfat dry milk reduces weight gain and associated adipose tissue inflammation in diet-induced obese mice when compared to high calcium alone

Anthony Thomas — 2012-01-23T00:00:00Z

Background: High dietary calcium (Ca) is reported to have anti-obesity and anti-inflammatory properties. Evidence for these properties of dietary Ca in animal models of polygenic obesity have been confounded by the inclusion of dairy food components in experimental diets; thus, effect of Ca per se could not be deciphered. Furthermore, potential anti-inflammatory actions of Ca in vivo could not be dissociated from reduced adiposity. Methods: We characterized adiposity along with metabolic and inflammatory phenotypes in diet-induced obese (DIO) mice fed 1 of 3 high fat diets (45% energy) for 12 wk: control (n = 29), high-Ca (n = 30), or high-Ca + nonfat dry milk (NFDM) (n = 30). Results: Mice fed high-Ca + NFDM had reduced body weight and adiposity compared to high-Ca mice (P < 0.001). Surprisingly, the high-Ca mice had increased adiposity compared to lower-Ca controls (P < 0.001). Hyperphagia and increased feed efficiency contributed to obesity development in high-Ca mice, in contrast to NFDM mice that displayed significantly reduced weight gain despite higher energy intake compared to controls (P<0.001). mRNA markers of macrophages (e.g., CD68, CD11d) strongly correlated with body weight in all diet treatment groups, and most treatment differences in WAT inflammatory factor mRNA abundances were lost when controlling for body weight gain as a covariate. Conclusions: The results indicate that high dietary Ca is not sufficient to dampen obesity-related phenotypes in DIO mice, and in fact exacerbates weight gain and hyperphagia. The data further suggest that putative anti-obesity properties of dairy emanate from food components beyond Ca.

Population prevalence, attributable risk, and attributable risk percentage for high methylmalonic acid concentrations in the post-folic acid fortification period in the US

Vijay Ganji — 2012-01-11T00:00:00Z

Background: Serum methylmalonic acid (MMA) is regarded as a sensitive marker of vitamin B-12 status. Elevated circulating MMA is linked to neurological abnormalities. Contribution of age, supplement use, kidney dysfunction, and vitamin B-12 deficiency to high serum MMA in post-folic acid fortification period is unknown. Methods: We investigated prevalence, population attributable risk (PAR), and PAR% for high MMA concentrations in the US. Data from 3 cross-sectional National Health and Nutrition Examination Surveys conducted in post-folic acid fortification period were used (n=18569). Results: Likelihood of having high serum MMA for white relative to black was 2.5 (P<0.0001), [greater than or equal to]60 y old persons relative to <60 y old persons was 4.0 (P<0.0001), non-supplement users relative to supplement users was 1.8 (P<0.0001), persons with serum creatinine [greater than or equal to]130 umol/L relative to those with <130 umol/L was 12.6 (P<0.0001), and persons with serum vitamin B-12 <148 pmol/L relative to those with [greater than or equal to]148 pmol/L was 13.5 (P<0.0001). PAR% for high MMA for old age, vitamin B-12 deficiency, kidney dysfunction, and non-supplement use were 40.5, 16.2, 13.3, and 11.8, respectively. By improving serum vitamin B-12 ([greater than or equal to]148 pmol/L), prevalence of high MMA would be reduced by 16-18% regardless of kidney dysfunction. Conclusions: Old age is the strongest determinant of PAR for high MMA. About 5 cases of high serum MMA/1000 people would be reduced if vitamin B-12 deficiency (<148 pmol/L) is eliminated. Large portion of high MMA cases are not attributable to serum vitamin B-12. Thus, caution should be used in attributing high serum MMA to vitamin B-12 deficiency.

Gamma-tocotrienol does not substantially protect DS neurons from hydrogen peroxide-induced oxidative injury

Sue-Mian Then — 2012-01-05T00:00:00Z

Background: Down syndrome (DS) neurons are more susceptible to oxidative stress and previous studies have shown that vitamin E was able to reduce oxidative stress and improve DS neurons' viability. Therefore, this study was done to investigate the protective role of gamma-tocotrienol (gT3) in DS neurons from hydrogen peroxide (H2O2) -induced oxidative stress. The pro-apoptosis tendency of gT3 was compared to alpha-tocopherol (aT) in non-stress condition as well. Methods: Primary culture of DS and euploid neurons were divided into six groups of treatment: control, H2O2, gT3 pre-treatment with H2O2, gT3 only, aT pre-treatment with H2O2 and aT only. The treatments were assessed by MTS assay and apoptosis assay by single-stranded DNA (ssDNA) apoptosis ELISA assay, Hoechst and NeuN immunofluorescence staining. The cellular uptake of gT3 and aT were determined by HPLC while protein expressions were determined by Western blot. Comparison between groups was made by the Student's t test, one-way ANOVA and Bonferroni adjustment as well as two-way ANOVA for multiple comparisons. Results: One day incubation of gT3 was able to reduced apoptosis of DS neurons by 10%, however gT3 was cytotoxic at longer incubation period (14 days) and at concentrations [greater than or equal to]100uM. Pre-treatment of aT and gT3 only attenuate apoptosis and increase cell viability in H2O2-treated DS and euploid neurons by 10% in which the effects were minimal to maintain most of the DS cells' morphology. gT3 act as a free radical scavenger by reducing ROS generated by H2O2. In untreated controls, DS neurons showed lower Bcl-2/Bax ratio and p53 expression compared to normal neurons, while cPKC and PKC-delta expressions were higher in DS neurons. On the other hand, pre-treatment of gT3 in H2O2-treated DS neurons have reduced Bcl-2/Bax ratio, which was not shown in euploid neurons. This suggests that pre-treatment of gT3 did not promote DS cell survival. Meanwhile gT3 and aT treatments without H2O2 as well as pre-treatment of gT3 and aT induced changes in cPKC and PKC-delta expression in DS neurons suggesting interaction of gT3 and aT with PKC activity. Conclusion: Our study suggests that gT3 pre-treatment are not sufficient to protect DS neurons from H2O2-induced oxidative assault, instead induced the apoptosis process.

Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

Maaike Oosterveer — 2011-12-27T00:00:00Z

Background Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant to high fat diet-induced adiposity. Whether this phenotype of CB1-/- mice is related to altered fat metabolism in adipose tissue is unknown. Methods We evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of CB1-/- and CB1+/+ mice fed a high-fat (HF) or a high-fat/fish oil (HF/FO) diet as compared to animals receiving a low-fat chow diet. Comparison between HF diet and HF/FO diet allowed to investigate the influence of dietary fat quality on adipose tissue biology in relation to CB1 functioning. Results The adiposity-resistant phenotype of the CB1-/- mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB1-/- mice in parallel to a significant increase in energy expenditure as compared to CB1+/+ mice. The expression levels of adipocyte differentiation and proliferation markers were however maintained in these animals. Consistent with unaltered lipogenic gene expression, the fatty acid synthesis rates in adipose tissues from CB1-/- and CB1+/+ mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL) activities were also not altered in CB1-/- mice. Conclusions These findings indicate that protection against diet-induced adiposity in CB1-deficient mice is not related to changes in adipocyte function per se, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.