Abstract The modern Western diet (MWD) provides high linoleic acid (LA) exposure, typically contributing 6–9% of total caloric intake. These high LA levels have fueled a longstanding debate regarding whether this dietary pattern confers benefit or risk. Importantly, LA intake is disproportionately elevated among lower socioeconomic populations due to greater reliance on industrial seed oils and ultra-processed foods. Despite decades of research, controlled dietary intervention studies directly evaluating the biological consequences of varying LA exposure remain limited. The current randomized, double-blind intervention compared the effects of a 12-week Low LA diet (2.5% energy) versus a High LA diet (10.0% energy) in healthy adults. Primary outcomes included plasma highly unsaturated fatty acid (HUFA) concentrations and ex vivo zymosan-stimulated whole-blood oxylipin generation. Fifty- two participants completed the intervention. High LA exposure resulted in a marked reduction in plasma n-3 eicosapentaenoic acid (EPA) concentrations compared with the LowLA arm. In contrast, levels of arachidonic acid (ARA), dihomo-gamma-linolenic acid (DGLA) and docosahexaenoic acid (DHA) did not differ by dietary LA exposure. Analysis of oxylipin species revealed that levels of EPA-derived relative to ARA-derived mediators were significantly reduced in the High LA arm. These findings reveal that higher dietary LA selectively suppresses EPA pools and EPA-derived oxylipins without altering ARA, shifting the lipid mediator balance toward a more n-6-dominant profile.

The development and progression of nutrition as a scientific field is ever evolving and complex. Although the history of nutrition research began by exploring specific food components, it has evolved to encompass a more holistic view that considers the impact of dietary patterns over time, interactions with the environment, nutrition's role in disease processes, and public policy related to nutrition health. To guide the future direction of nutrition science, both federal and other professional organizations have established agendas and goals. The Strategic Plan for National Institutes of Health Nutrition Research outlines four goals and five cross-cutting research areas that are priorities to explore between 2020 and 2030. Similarly, the American Society for Parenteral and Enteral Nutrition and other governmental and professional organizations have identified priority areas in their research agendas. Rigorous research studies are needed to explore these areas of interest while also considering practical implementation strategies for translating research into practice. Nutrition clinicians are uniquely positioned to lend expertise in the areas of research design, implementation, advocacy and evidence-based practice; there are numerous resources to support practitioners in these endeavors.

Abstract BACKGROUND There has been increasing interest in exploring ketogenic diet therapies (KDT) in patients with glioma given the poor prognosis. The purpose of this single-arm, open label phase 2 study was to rigorously examine the feasibility, safety, systemic biological activity, and cerebral activity of a KDT in patients with glioma. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease following adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 fasting days (calories<20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates≤20 gm/day) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, IGF-1, and MR spectroscopy at baseline and week 8. RESULTS 21 patients completed the study. 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% of patients were adherent by food record. The diet was well-tolerated with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity including hemoglobin A1c, insulin, and fat body mass decreased significantly, while lean body mass increased. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Higher total choline (tCho) and glutamine (Gln) levels were observed in lesional as compared to contralateral brain at baseline, and both decreased following intervention. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs0.52, p=0.05). There were no differences in cerebral metabolites in IDH-mutant glioma after controlling for ketonuria. CONCLUSIONS The GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Participant ketonuria correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records.

Objective To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma. Methods Twenty-five patients with biopsy-confirmed World Health Organization grade 2 to 4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week Glioma Atkins-Based Diet (GLAD). GLAD consisted of 2 fasting days (calories <20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates ≤20 g/d) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, insulin-like growth factor-1, and magnetic resonance spectroscopy at baseline and week 8. Results Twenty-one patients (84%) completed the study. Eighty percent of patients reached ≥40 mg/dL urine acetoacetate during the study. Forty-eight percent of patients were adherent by food record. The diet was well tolerated, with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity, including hemoglobin A1c, insulin, and fat body mass, decreased significantly, while lean body mass increased. Magnetic resonance spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate [bHB] and acetone) in both lesional and contralateral brain compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs = 0.52, p = 0.05). Subgroup analysis of isocitrate dehydrogenase–mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria. Conclusion The GLAD dietary intervention, while demanding, produced meaningful ketonuria and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records. Trial Registration Information ClinicalTrials.gov Identifier: NCT02286167.

Abstract INTRODUCTION Exploiting metabolic vulnerabilities via ketosis is a promising approach for gliomas. The modified Atkins diet is a ketogenic diet therapy efficacious in adults with refractory epilepsy. We evaluated the feasibility, pharmacokinetics/pharmacodynamics(PK/PD), and cerebral activity of this dietary intervention intended to induce ketosis. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 ‘intermittent fasting’ days(IF; calories < 20% of recommended daily allowance) interleaved between 5 modified-Atkins diet days(MAD; carbohydrates < 20 gm/day) each week. The primary outcome was dietary compliance. Secondary outcomes were PK assessed by urine ketones post-FAST and post-MAD, PD assessed by serum insulin and IGF-1, and cerebral activity measured by MR spectroscopy at baseline and week 8. RESULTS Grade 2(n=2;8%), Grade 3(n=11;44%) and GBMs(n=12;48%) were enrolled. While only 48% of participants satisfied pre-defined compliance criteria, overall compliance with MAD(80%) was higher than IF(72%). Weight loss was observed (-4.8 + 2.2kg,p< 0.0001) consisting primarily of decreased fat mass (-2.5 + 3.1%,p< 0.0001), with increased lean body mass (2.4 + 3.2%,p< 0.0001), stable nutritional status (phase angle, -0.26 + 0.94%,p=0.22), and normalization of BMI. Urine acetoacetate significantly increased with 55% achieving moderate ketosis at week 8 (p=0.0005). Serum insulin and IGF-1 significantly decreased indicating systemic dietary response and were associated with higher ketones post-IF, but not post-MAD. MRS demonstrated cerebral activity with increased ketones in lesional (0.06±0.03- >0.27±0.06i.u,p=0.005) and contralateral brain at week 8 (0.041±0.01- >0.16±0.04i.u.,p=0.004). Higher cerebral acetone correlated with higher urine ketones (r >0.75,p< 0.02) and lower fasting glucose (r >-0.74,p< 0.05). CONCLUSIONS The GLAD diet was challenging to maintain but demonstrated quantifiable biologic effects systemically and intratumorally. MAD was more feasible than IF, but changes in PD markers correlated most strongly with IF. The role of ketogenic diet therapy for preventing glioma growth remains uncertain.

April 27, 2018April 10, 2018Free AccessAssessing cerebral metabolic activity of an Atkins-based diet using MR Spectroscopy – A feasibility study in glioma patients (P6.146)Karisa Schreck, Adam Berrington, Bobbie Henry-Barron, Lindsay Blair, Adam Hartman, Eric Kossoff, Linda Easter, … Show All … , Chris Whitlow, Fang-Chi Hsu, Mackenzie Cervenka, Jaishri Blakeley, Peter Barker, and Roy Strowd Show FewerAuthors Info & AffiliationsApril 10, 2018 issue90 (15_supplement) Letters to the Editor

There is renewed interest in exploring treatment strategies which target metabolic pathways involved in gliomagenesis, including ketogenic diets. The purpose of this pilot study was to evaluate the feasibility of proton MR spectroscopy (MRS) to detect the cerebral metabolic activity of an 8-week GLioma Atkins-based Diet (GLAD) in patients with glioma. Patients with grade 3-4 astrocytoma were enrolled after completing adjuvant chemotherapy, before first recurrence. GLAD consisted of 20gm carbohydrate restriction (modified Atkins diet) along with 2 days per week of intermittent fasting (caloric restriction to 20% recommended daily allowance). MRS was performed in both the lesion and a mirror voxel in the contralateral hemisphere at baseline and week 8. Data were analyzed using the ‘LCModel’ program using a basis set of three ketone bodies (acetone (Ace), beta-hydroxybutyrate (BHB), acetoacetate (AcAc)), 2-hydroxyglutarate (2-HG), citrate (Cit), and some standard metabolites. Interim analysis is reported after 12 patients enrolled; mean age 49 ± 11 years; 8 male; 5 grade IV astrocytomas. Two patients did not complete the study; two were excluded for incomplete data. As expected, concentrations of tNAA (p<0.028) and Lac (p<0.023) were different between lesion and normal brain at baseline. Ketone body concentrations were nearly undetectable at baseline; however by week 8, Ace and BHB were reliably detected in both lesion ([Ace]=0.08->0.32 ± 0.19, p=0.005; [BHB]=0.07->0.6 ± 0.68, p=0.05) and contralateral brain ([Ace]=0.01->0.16 ± 0.14, p=0.015; [BHB]=0->0.23 ± 0.25, p=0.021). In the lesion, BHB rose by 1.0mM from baseline to Week 8 in IDH1 mutant as compared to a decrease by -0.13mM in wild-type astrocytomas (p<0.002). The increase in BHB but not Ace was also significantly greater in patients with higher dietary compliance as measured by urine ketones (p<0.03). These preliminary results demonstrate the ability of brain MRS to monitor the metabolic consequences of a ketogenic diet in patients with high-grade glioma.

Context: Compared with European Americans, African Americans (AAs) are more insulin resistant, have a higher insulin secretion response to glucose, and develop type 2 diabetes more often. Molecular processes and/or genetic variations contributing to altered glucose homeostasis in high-risk AAs remain uncharacterized.Objective: Adipose and muscle transcript expression profiling and genotyping were performed in 260 AAs to identify genetic regulatory mechanisms associated with insulin sensitivity (SI). We hypothesized that: 1) transcription profiles would reveal tissue-specific modulation of physiologic pathways with SI, and 2) a subset of SI-associated transcripts would be controlled by DNA sequence variants as expression quantitative traits, and these variants in turn would be associated with SI.Design and Settings: The cross-sectional research study was performed in a clinical research unit.Participants: Unrelated nondiabetic AAs were recruited for the study.Main Outcome Measures: SI was measured by frequently sampled iv glucose tolerance test.Results: The expression levels of 2212 transcripts in adipose and 145 transcripts in muscle were associated with SI. Genes involved in eIF2, eIF4-p70S6K, and mTOR signaling were modulated with S-I in both tissues. Genes involved in leukocyte extravasation signaling showed adipose-specific regulation, and genes involved in oxidative phosphorylation had discordant regulation between tissues. Intersecting cis-expression quantitative trait loci results with data from transcript-S-I association analysis identified cis-regulatory single nucleotide polymorphisms for 363 and 42 S-I-associated transcripts in adipose and muscle, respectively. Cis-eSNPs for three SI-associated adipose transcripts, NINJ1, AGA, and CLEC10A were associated with S-I. Abrogation of NINJ1 induction in THP1 macrophages modulated expression of genes in chemokine signaling, cell adhesion, and angiogenesis pathways.Conclusion: This study identified multiple pathways associated with S-I; particularly discordant tissue-specific regulation of the oxidative phosphorylation pathway, and adipose-specific regulation of transcripts in the leukocyte extravasation signaling pathway that seem to be important in insulin resistance. Identification of single nucleotide polymorphisms associated with S-I and with modulation of expression of S-I-associated transcripts, including NINJ1, reveals novel genetic regulatory mechanisms of insulin resistance in AAs.

Background: Hyperoxaluria may result from increased endogenous production or overabsorption of dietary oxalate in the gastrointestinal tract leading to nephrolithiasis and, in some, to oxalate nephropathy and chronic kidney disease. ALLN-177 is an oral formulation of a recombinant, oxalate specific, microbial enzyme oxalate decarboxylase intended to treat secondary hyperoxaluria by degrading dietary oxalate in the gastrointestinal tract, thereby reducing its absorption and subsequent excretion in the urine. Methods: This double-blind, placebo controlled, randomized, cross-over, phase 1 study of ALLN-177 evaluated the tolerability of ALLN-177 and its effect on urinary oxalate excretion in 30 healthy volunteers with hyperoxaluria induced by ingestion of a high oxalate, low calcium (HOLC) diet. The primary end point was the difference in the mean 24-hour urinary oxalate excretion during the ALLN-177 treatment period compared with the placebo treatment period. Results: The daily urinary oxalate excretion increased in the study population from 27.2 ± 9.5 mg/day during screening to 80.8 ± 24.1 mg/day (mean ± SD) on the HOLC diet before introducing ALLN-177 or placebo therapy for 7 days. Compared to placebo, ALLN-177 treatment reduced urinary oxalate by 11.6 ± 2.7 mg/day, p = 0.0002 (least squares mean ± SD). Conclusions: In healthy volunteers, with diet-induced hyperoxaluria treatment with ALLN-177, when compared to placebo, significantly reduced urinary oxalate excretion by degrading dietary oxalate in the gastrointestinal tract and thereby reducing its absorption. ALLN-177 may represent a new approach for managing secondary hyperoxaluria and its complications.

OBJECTIVE To determine if fish oil supplementation reduces endogenous oxalate synthesis in healthy subjects.MATERIALS AND METHODS Fifteen healthy non-stone-forming adults participated in this study. Subjects first abstained from using vitamins, medications, or foods enriched in omega-3 fatty acids for 30 days. Next, they collected two 24-hour urine specimens while consuming a self-selected diet. Subjects consumed an extremely low-oxalate and normal-calcium diet for 5 days and collected 24-hour urine specimens on the last 3 days of this diet. Next, the subjects took 2 fish oil capsules containing 650-mg eicosapentaenoic acid and 450-mg docosahexaenoic acid twice daily for 30 days. They consumed a self-selected diet on days 1-25 and the controlled diet on days 26-30. Twenty-four-hour urine samples were collected on days 28-30. Excretion levels of urinary analytes including oxalate and glycolate were analyzed.RESULTS Although there was a significant reduction in urinary oxalate, magnesium, and potassium excretions and an increase in uric acid excretion during the controlled dietary phases compared with the self-selected diet, there were no significant differences in their excretion during controlled diet phases with and without fish oil supplementation.CONCLUSION These results suggest that fish oil supplementation does not reduce endogenous oxalate synthesis or urinary oxalate excretion in normal adults during periods of extremely low oxalate intake. However, these results do not challenge the previously described reduction in urinary oxalate excretion demonstrated in normal subjects consuming a moderate amount of oxalate in conjunction with fish oil. (C) 2014 Elsevier Inc.

Intestinal fat absorption is known to be, overall, a highly efficient process, but much less is known about the efficiency with which individual dietary fatty acids (FA) are absorbed by the adult small intestine. We therefore measured the absorption efficiency of the major dietary FA using sucrose polybehenate (SPB) as a nonabsorbable marker and analyzed how it is modulated by acyl chain physicochemical properties and polymorphisms of proteins involved in chylomicron assembly. Dietary FA absorption efficiency was measured in 44 healthy subjects fed a standard diet containing 35% fat and 5% SPB. FA and behenic acid (BA) were measured in homogenized diets and stool samples by gas chromatography-mass spectroscopy, and coefficients of absorption for each FA were calculated as 1 - [(FA/BA)feces/(FA/BA)diet]. Absorption coefficients for saturated FA decreased with increasing chain length and hydrophobicity (mean ± SE) and ranged from 0.95 ± 0.02 for myristate (14:0), 0.80 ± 0.03 for stearate (18:0), to 0.26 ± 0.02 for arachidate (20:0). Absorption coefficients for unsaturated FA increased with increasing desaturation from 0.79 ± 0.03 for elaidic acid (18:1t), 0.96 ± 0.01 for linoleate (18:2), to near complete absorption for eicosapentaenoic (20:5) and docosahexaenoic (22:6) acids. Of several common genetic polymorphisms in key proteins involved in the chylomicron assembly pathway, only the intestinal fatty acid-binding protein-2 A54T allele (rs1799883) had any impact on FA absorption. We conclude that acyl chain length, saturation, and hydrophobicity are the major determinants of the efficiency with which dietary FA are absorbed by the adult small intestine.

INTRODUCTION:Certain dietary modifications limit the risk of stone recurrence. Compliance is an important component of dietary therapy for stone prevention, and self-efficacy is an important ingredient of compliance. We developed an internet program to facilitate dietary compliance for stone prevention and performed a pilot study to assess its effectiveness.MATERIALS AND METHODS:The internet program provides information regarding dietary modifications including increased fluid consumption, limited animal protein, sodium, and oxalate intake, and adequate calcium consumption. Participants record their daily food and fluid intake and receive immediate feedback as to whether they were compliant or not. Five adult calcium stone formers collected three 24 hour urine specimens on self-selected diets, three 24 hour urine specimens while on a stone preventive metabolic diet, and three 24 hour urine specimens after utilizing the internet program for 1 month. Urinary stone risk parameters were measured, and data were analyzed using repeated measures ANOVA and Student's t test.RESULTS:All participants recorded their meals and snacks for each day and found the program easy to navigate. The mean time in hours from food consumption to log in was 35.25 +/- 70.8 hours. There were no statistically significant differences in stone risk factors between the controlled and internet dietary phases. Oxalate excretion was significantly higher during the self-selected dietary intake (p = 0.03).CONCLUSIONS:This pilot study demonstrates that subjects appear to be compliant with utilization of an interactive internet program for stone prevention with dietary modifications. In addition, improvement in certain stone risk parameters occurred.

You have accessJournal of UrologyStone Disease: Evaluation & Medical Management (II)1 Apr 20132255 THE IMPACT OF FISH OIL SUPPLEMENTATION ON ENDOGENOUS OXALATE SYNTHESIS AND URINARY OXALATE EXCRETION Jessica Lange, Patrick Mufarrij, Linda Easter, John Knight, Ross Holmes, and Dean Assimos Jessica LangeJessica Lange Winston-Salem, NC More articles by this author , Patrick MufarrijPatrick Mufarrij Winston-Salem, NC More articles by this author , Linda EasterLinda Easter Winston-Salem, NC More articles by this author , John KnightJohn Knight Birmingham, AL More articles by this author , Ross HolmesRoss Holmes Birmingham, AL More articles by this author , and Dean AssimosDean Assimos Birmingham, AL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2164AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It has been recently reported that the administration of fish oil supplements to non-hyperoxaluric, healthy adults consuming metabolic diets with normal oxalate and calcium content resulted in a significant reduction in urinary oxalate excretion. The mechanism of this response has not been defined, but we hypothesize that it is due to a reduction in endogenous oxalate synthesis via its anti-inflammatory and antioxidant properties. METHODS Fifteen healthy, non-stone forming, non-hyperoxaluric adults participated (mean age 25.3 ± 2.7 years, BMI < 30, 8 male, 7 female) in this study. First, subjects were asked to abstain from utilization of any supplements, vitamins, medications, or foods enriched in omega 3 fatty acids for thirty days. After this, they collected two random baseline 24 hour urine specimens while eating a self-selected diet. Next, the subjects consumed a controlled low oxalate diet for five days. This was intended to reflect baseline endogenous oxalate production. The diet contained 50 mg oxalate, 1000 mg calcium, 3500 mg sodium, 300 mg magnesium, 1500 mg phosphorus, 3000 mg potassium, 125 mg vitamin C, and 2.5 liters of fluid per day. Subjects collected three 24 hour urine specimens on days three through five of this controlled diet phase. Next, they began taking two fish oil supplement capsules twice daily for 30 days (2600 mg eicosapentaenoic acid and 1800 mg docosahexaenoic acid per day) while consuming self-selected diets for 25 days. On days 26-30, they continued on fish oil and consumed the aforementioned controlled low oxalate diet. They collected 24 hour urine specimens on days 28-30. Statistical analysis included repeated measures ANOVA and Student's t test. RESULTS Analysis of the 24 hour urine collection data revealed no significant differences in urine volume, creatinine, or calcium between the baseline and metabolic dietary phases without and with fish oil. ANOVA analysis of daily oxalate excretion was significant (p < 0.01). While the Student's t test revealed a significant decrease in oxalate excretion between the self-selected diet and both controlled dietary phases (p < 0.01), there was no significant difference between the controlled diet phases without or with fish oil supplementation. CONCLUSIONS These results suggest that fish oil supplementation does not impact endogenous oxalate synthesis in healthy adults without hyperoxaluria. Thus, the reduction previously reported in this cohort could be due to alterations in gastrointestinal or renal handling of oxalate. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189 Issue 4S April 2013 Page: e925 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Metrics Author Information Jessica Lange Winston-Salem, NC More articles by this author Patrick Mufarrij Winston-Salem, NC More articles by this author Linda Easter Winston-Salem, NC More articles by this author John Knight Birmingham, AL More articles by this author Ross Holmes Birmingham, AL More articles by this author Dean Assimos Birmingham, AL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

OBJECTIVE To determine whether the ratio of dietary calcium and oxalate consumption at mealtime affects gastrointestinal oxalate absorption and urinary oxalate excretion.METHODS A study was conducted with 10 non-stone-forming adults placed on controlled diets with daily calcium and oxalate contents of 1000 and 750 mg, respectively. Subjects consumed a balanced calcium/oxalate ratio diet for 1 week, observed a minimum 1-week washout period, and subsequently consumed an imbalanced calcium/oxalate ratio diet for one week. Urine specimens were collected on the last 4 days of each diet. Outcome measures included urinary creatinine, calcium, and oxalate as well as the Tiselius index for assessing urinary calcium oxalate supersaturation.RESULTS Total daily calcium excretion, oxalate excretion, and Tiselius index were similar between balanced and imbalanced dietary phases. There were significant differences in calcium excretion (mg/g creatinine) between balanced and imbalanced diets in the 1-6 PM (83.1 vs 110.2, P <.04), 6-11 PM (71.3 vs 107.2, P <.02), and 11 PM-8 AM collections (55.0 vs 41.8, P <.02). There was significantly higher oxalate excretion on the balanced diet in the 1-6 PM time period (28.1 vs 16.7, P <.01). There were no differences in the Tiselius index in these collections.CONCLUSION These results demonstrate that the sequence of ingesting relatively large amounts of oxalate does not significantly affect calcium oxalate stone risk if the recommended daily quantity of dietary calcium is consumed. UROLOGY 79: 1226-1229, 2012. (c) 2012 Elsevier Inc.

BACKGROUNDExercise intensity may affect the selective loss of abdominal adipose tissue.OBJECTIVEThis study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity.DESIGNThis was a randomized trial in 112 overweight and obese [body mass index (in kg/m(2)): 25-40; waist circumference >88 cm], postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit: calorie restriction (CR only), CR plus moderate-intensity aerobic exercise (CR + moderate-intensity), or CR plus vigorous-intensity exercise (CR + vigorous-intensity). The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels (approximately 400 kcal/d). Exercise (3 d/wk) involved treadmill walking at an intensity of 45-50% (moderate-intensity) or 70-75% (vigorous-intensity) of heart rate reserve. The primary outcome was abdominal visceral fat volume.RESULTSAverage weight loss for the 95 women who completed the study was 12.1 kg (+/-4.5 kg) and was not significantly different across groups. Maximal oxygen uptake ( O(2)max) increased more in the CR + vigorous-intensity group than in either of the other groups (P < 0.05). The CR-only group lost relatively more lean mass than did either exercise group (P < 0.05). All groups showed similar decreases in abdominal visceral fat (approximately 25%; P < 0.001 for all). However, changes in visceral fat were inversely related to increases in O(2)max (P < 0.01). Changes in lipids, fasting glucose or insulin, and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups.CONCLUSIONWith a similar amount of total weight loss, lean mass is preserved, but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction. This trial was registered at (ClinicalTrials.gov) as: NCT00664729.

Concentrations of oxalate-degrading anaerobes in ruminal contents of sheep were determined from counts of colonies producing clear zones on a calcium oxalate medium (D agar with 7 mM CaCl2). Viable counts of oxalate degraders from a 55-kg sheep fed a diet containing 32% halogeton (4.6% oxalate) averaged 2.6 × 106 / g (dry weight). When the halogeton concentration in the diet was reduced to 16%, counts of oxalate degraders decreased nearly 300-fold. Oxalate-degrading isolates from this sheep were similar to OxB, the type strain of Oxalobacter formigenes. When a 45-kg sheep was fed diets containing 2.2, 1.5, and 0.8% oxalate, viable counts of oxalate degraders (enumerated on D agar with 14 mM CaCl2 and 20% filter-sterilized ruminal fluid) represented 0.85, 0.52, and 0.06% of the total viable population, respectively; total viable counts were essentially unchanges by these concentrations of dietary oxalate. Similar percentages of oxalate degraders were also observed when a 23-kg sheep was fed diets containing 1.5 or 0.8% oxalate. This report presents the first direct measurements of the concentrations of oxalate-degrading bacteria in the rumen and supports the concept that the availability of oxalate in the diet influences the proportion of oxalate-degrading bacteria in the rumen

K m (≈20 mM) and V max (≈1200 nmol/mg protein), suggesting recruitment of another carrier system in apical membrane.Phloretin, a GLUT2 inhibitor, significantly inhibited glucose uptake, especially at high glucose concentration and in incubation durations of >1 min raising the possibility that the increased K m and V max were due to translocation of GLUT2.Western blotting of the apical membrane using antibodies against SGLT-1 and GLUT2 suggested that GLUT2 rather than SGLT-1 translocated to apical membrane.Nocodazole inhibited carrier-mediated glucose uptake at high glucose concentrations (25 and 50 mM) during the 5 and 10 min incubation, but not at low glucose concentrations (0.5-10 mM) or with short durations of exposure (30 s and 1 min).CONCLUSION: GLUT2 is translocated to the intestinal apical membrane of Caco-2 cells via a glucose-dependent mechanism acting via the microtubular system.