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BACKGROUND: Oleic acid (OA) is oxidized more rapidly than is palmitic acid (PA). OBJECTIVE: We hypothesized that changing the dietary intakes of PA and OA would affect fatty acid oxidation and energy expenditure. DESIGN: A double-masked trial was conducted in 43 healthy young adults, who, after a 28-d, baseline, solid-food diet (41% of energy as fat, 8.4% as PA, and 13.1% as OA), were randomly assigned to one of two 28-d formula diets: high PA (40% of energy as fat, 16.8% as PA, and 16.4% as OA; n = 21) or high OA (40% of energy as fat, 1.7% as PA, and 31.4% as OA; n = 22). Differences in the change from baseline were evaluated by analysis of covariance. RESULTS: In the fed state, the respiratory quotient was lower (P = 0.01) with the high OA (0.86 +/- 0.01) than with the high-PA (0.89 +/- 0.01) diet, and the rate of fat oxidation was higher (P = 0.03) with the high-OA (0.0008 +/- 0.0001) than with the high-PA (0.0005 +/- 0.0001 mg x kg fat-free mass(-1) x min(-1)) diet. Resting energy expenditure in the fed and fasting states was not significantly different between groups. Change in daily energy expenditure in the high-OA group (9 +/- 60 kcal/d) was significantly different from that in the high-PA group (-214 +/- 69 kcal/d; P = 0.02 or 0.04 when expressed per fat-free mass). CONCLUSIONS: Increases in dietary PA decrease fat oxidation and daily energy expenditure, whereas decreases in PA and increases in OA had the opposite effect. Increases in dietary PA may increase the risk of obesity and insulin resistance. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Importance: Pediatric obesity is a growing health care burden. Understanding how the metabolic phenotype of youth with obesity may modify the effect of intestinal fermentation on human metabolism is key to designing early intervention., Objective: To assess whether adiposity and insulin resistance in youth may be associated with colonic fermentation of dietary fibers and its production of acetate, gut-derived hormone secretion, and adipose tissue lipolysis., Design, Setting, and Participants: Cross-sectional study of youths aged 15 to 22 years with body mass index in the 25th to 75th percentile or higher than the 85th percentile for age and sex throughout the New Haven County community in Connecticut. Recruitment, studies, and data collection occurred from June 2018 to September 2021. Youths were assigned to a lean, obese insulin sensitive (OIS), or obese insulin resistant (OIR) group. Data were analyzed from April 2022 to September 2022., Exposure: Participants consumed 20 g of lactulose during a continuous 10-hour sodium d3-acetate intravenous infusion to measure the rate of appearance of acetate in plasma., Main Outcomes and Measures: Plasma was obtained hourly to measure acetate turnover, peptide tyrosine tyrosine (PYY), ghrelin, active glucagon-like peptide 1 (GLP-1), and free fatty acids (FFA)., Results: A total of 44 youths participated in the study (median [IQR] age, 17.5 [16.0-19.3] years; 25 [56.8%] were female; 23 [52.3%] were White). Consequent to lactulose ingestion, there was a reduction of plasma FFA, an improvement of adipose tissue insulin sensitivity index, an increase in colonic acetate synthesis, and an anorexigenic response characterized by an increased plasma concentration of PYY and active GLP-1 and a reduction of ghrelin in the subgroups. Compared with the lean and OIS groups, the OIR group showed a less marked median (IQR) rate of acetate appearance (OIR: 2.00 [-0.86 to 2.69] μmol × kg-1 × min-1; lean: 5.69 [3.04 to 9.77] μmol × kg-1 × min-1; lean vs OIR P = .004; OIS: 2.63 [1.22 to 4.52] μmol × kg-1 × min-1; OIS vs OIR P = .09), a blunted median (IQR) improvement of adipose insulin sensitivity index (OIR: 0.043 [ 0.006 to 0.155]; lean: 0.277 [0.220 to 0.446]; lean vs OIR P = .002; OIS: 0.340 [0.048 to 0.491]; OIS vs OIR P = .08), and a reduced median (IQR) PYY response (OIR: 25.4 [14.8 to 36.4] pg/mL; lean: 51.3 [31.6 to 83.3] pg/mL; lean vs OIR P = .002; OIS: 54.3 [39.3 to 77.2] pg/mL; OIS vs OIR P = .011)., Conclusions and Relevance: In this cross-sectional study, lean, OIS, and OIR youth demonstrated different associations between colonic fermentation of indigestible dietary carbohydrates and the metabolic response, with OIR youth showing minimal metabolic modifications as compared with the other 2 groups., Trial Registration: ClinicalTrials.gov Identifier: NCT03454828.

Prior studies in younger adults showed that reducing the normally high intake of the saturated fatty acid, palmitic acid (PA), in the North American diet by replacing it with the monounsaturated fatty acid, oleic acid (OA), decreased blood concentrations and secretion by peripheral blood mononuclear cells (PBMCs) of interleukin (IL)-1β and IL-6 and changed brain activation in regions of the working memory network. We examined the effects of these fatty acid manipulations in the diet of older adults. Ten subjects, aged 65-75 years, participated in a randomized, cross-over trial comparing 1-week high PA versus low PA/high OA diets. We evaluated functional magnetic resonance imaging (fMRI) using an N-back test of working memory and a resting state scan, cytokine secretion by lipopolysaccharide (LPS)-stimulated PBMCs, and plasma cytokine concentrations. During the low PA compared to the high PA diet, we observed increased activation for the 2-back minus 0-back conditions in the right dorsolateral prefrontal cortex (Broadman Area (BA) 9; p < 0.005), but the effect of diet on working memory performance was not significant (p = 0.09). We observed increased connectivity between anterior regions of the salience network during the low PA/high OA diet (p < 0.001). The concentrations of IL-1β (p = 0.026), IL-8 (p = 0.013), and IL-6 (p = 0.009) in conditioned media from LPS-stimulated PBMCs were lower during the low PA/high OA diet. This study suggests that lowering the dietary intake of PA down-regulated pro-inflammatory cytokine secretion and altered working memory, task-based activation and resting state functional connectivity in older adults., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: In the last few years, there has been a growing interest in the role of gut microbiota in the development of obesity and its complications., Objectives: In this study, we tested the following hypotheses: 1) lean youth and youth with obesity experience a different capability of their gut microbiota to ferment carbohydrates and produce acetate; and 2) colonic acetate may serve as a substrate for hepatic de novo lipogenesis (DNL)., Methods: Nineteen lean youth [mean ± SE BMI (in kg/m2): 21.8 ± 0.521] and 19 youth with obesity (BMI: 35.7 ± 1.66), ages 15-21 y, frequency-matched by age and sex, underwent a fasting 10-h sodium [d3]-acetate intravenous infusion to determine the rate of appearance of acetate (Raacet) into the peripheral circulation before and after an oral dose of 20 g of lactulose. Pre- and post-lactulose Raacet values were determined at a quasi-steady state and changes between groups were compared using a quantile regression model. Acetate-derived hepatic DNL was measured in 11 subjects (6 youth with obesity) and its association with Raacet was assessed using Spearman correlation., Results: Mean ± SE Raacet was not different before lactulose ingestion between the 2 groups (7.69 ± 1.02 μmol · kg-1 · min-1 in lean youth and 7.40 ± 1.73 μmol · kg-1 · min-1 in youth with obesity, P = 0.343). The increase in mean ± SE Raacet after lactulose ingestion was greater in lean youth than in youth with obesity (14.7 ± 2.33 μmol · kg-1 · min-1 and 9.29 ± 1.44 μmol · kg-1 · min-1, respectively, P = 0.001). DNL correlated with Raacet, calculated as changes from the pre- to the post-lactulose steady state (ρ = 0.621; P = 0.046)., Conclusions: These data suggest that youth with obesity ferment lactulose to a lesser degree than youth without obesity and that colonic acetate serves as a substrate for hepatic DNL.This trial was registered at clinicaltrials.gov as NCT03454828., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Pharmacokinetics (PK) of pharmaceuticals and pharmaconutrients are poorly understood in critically ill patients, and dosing is often based on healthy subject data. This might be particularly problematic with enteral medications due to metabolic abnormalities and impaired gastrointestinal tract absorption common in critically ill patients. Utilizing enteral fish oil, this study was undertaken to better understand and define PK of enteral omega-3 fatty acids (eicospentaenoic acid [EPA] and docosahexaenoic acid [DHA]) in critically ill patients with severe sepsis., Materials and Methods: Healthy volunteers (n = 15) and mechanically ventilated (MV) adults with severe sepsis (n = 10) were recruited and received 9.75 g EPA and 6.75 g DHA daily in two divided enteral doses of fish oil for 7 days. Volunteers continued their normal diet without other sources of fish oil, and sepsis patients received standard enteral feeding. Blood was collected at frequent intervals during the 14-day study period. Peripheral blood mononuclear cells (PMBCs) and neutrophils were isolated and analyzed for membrane fatty acid (FA) content. Mixed linear models and t-tests were used to analyze changes in FA levels over time and FA levels at individual time points, respectively. PK parameters were obtained based on single compartment models of EPA and DHA kinetics., Results: Healthy volunteers were 41.1 ± 10.3 years; 67% were women. In patients with severe sepsis (55.6 ± 13.4 years, 50% women), acute physiologic and chronic health evaluation (APACHE) II score was 27.2 ± 8.8 at ICU admission and median MV duration was 10.5 days. Serum EPA and DHA were significantly lower in sepsis vs. healthy subjects over time. PBMC EPA concentrations were generally not different between groups over time, while PBMC DHA was higher in sepsis patients. Neutrophil EPA and DHA concentrations were similar between groups. The half-life of EPA in serum and neutrophils was significantly shorter in sepsis patients, whereas other half-life parameters did not vary significantly between healthy volunteers and sepsis patients., Conclusions: While incorporation of n-3 FAs into PBMC and neutrophil membranes was relatively similar between healthy volunteers and sepsis patients receiving identical high doses of fish oil for one week, serum EPA and DHA were significantly lower in sepsis patients. These findings imply that serum concentrations and EPA and DHA may not be the dominant driver of leukocyte membrane incorporation of EPA and DHA. Furthermore, lower serum EPA and DHA concentrations suggest that either these n-3 FAs were being metabolized rapidly in sepsis patients or that absorption of enteral medications and pharmaconutrients, including fish oil, may be impaired in sepsis patients. If enteral absorption is impaired, doses of enteral medications administered to critically ill patients may be suboptimal., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Previous literature suggests that a higher ratio of palmitic acid (PA)/oleic acid (OA) in the diet induces inflammation, which may result in deficient brain insulin signaling, and, secondarily, impaired physical activity, sleep efficiency, and cognitive functioning., Objective: We hypothesized that lowering the typical dietary PA/OA would affect the activation of relevant brain networks during a working memory task and would also lower secretion of pro-inflammatory cytokines., Design: In 12 female subjects participating in a randomized, cross-over trial comparing 3-week high PA diet (HPA) and low PA and a high OA diet (HOA), we evaluated functional magnetic resonance imaging (fMRI) using an N-back test of working memory, cytokine secretion by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), and plasma cytokine concentrations., Results: Brain activation during the HPA diet compared to the HOA diet was increased in regions of the basal ganglia including the caudate and putamen (p<0.005). In addition, compared to the HOA diet, during the HPA diet, the plasma concentrations of IL-6 (p=0.04) and IL-1β (p=0.05) were higher, and there was a higher secretion of IL-18 (p=0.015) and a trend for higher IL-1β secretion (p=0.066) from LPS-stimulated PBMCs., Conclusions: The HPA diet resulted in increased brain activation in the basal ganglia compared to the HOA diet as well as increased secretion of pro-inflammatory cytokines. These data provide evidence that short-term (2week) diet interventions impact brain network activation during a working memory task and that these effects are reversible since the order of the study diets was randomized. These data are consistent with the hypothesis that lowering the dietary PA content via substitution with OA also could affect cognition., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We recently reported that lowering the high, habitual palmitic acid (PA) intake in ovulating women improved insulin sensitivity and both inflammatory and oxidative stress. In vitro studies indicate that PA can activate both cell membrane toll-like receptor-4 and the intracellular nucleotide oligomerization domain-like receptor protein (NLRP3). To gain further insight into the relevance to human metabolic disease of dietary PA, we studied healthy, lean and obese adults enrolled in a randomized, crossover trial comparing 3-week, high-PA (HPA) and low-PA/high-oleic-acid (HOA) diets. After each diet, both hepatic and peripheral insulin sensitivities were measured, and we assessed cytokine concentrations in plasma and in supernatants derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMCs) as well as proinflammatory gene expression in skeletal muscle. Insulin sensitivity was unaffected by diet. Plasma concentration of tumor necrosis factor-α was higher during the HPA diet. Lowering the habitually high PA intake by feeding the HOA diet resulted in lower secretion of interleukin (IL)-1β, IL-18, IL-10, and tumor necrosis factor-α by PBMCs, as well as lower relative mRNA expression of cJun and NLRP3 in muscle. Principal components analysis of 156 total variables coupled to analysis of covariance indicated that the mechanistic pathway for the differential dietary effects on PBMCs involved changes in the PA/OA ratio of tissue lipids. Our results indicate that lowering the dietary and tissue lipid PA/OA ratio resulted in lower leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes, but the relevance to diabetes risk is uncertain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Palmitic acid (PA) is associated with higher blood concentrations of medium-chain acylcarnitines (MCACs), and we hypothesized that PA may inhibit progression of FA β-oxidation. Using a cross-over design, 17 adults were fed high PA (HPA) and low PA/high oleic acid (HOA) diets, each for 3 weeks. The [1-(13)C]PA and [13-(13)C]PA tracers were administered with food in random order with each diet, and we assessed PA oxidation (PA OX) and serum AC concentration to determine whether a higher PA intake promoted incomplete PA OX. Dietary PA was completely oxidized during the HOA diet, but only about 40% was oxidized during the HPA diet. The [13-(13)C]PA/[1-(13)C]PA ratio of PA OX had an approximate value of 1.0 for either diet, but the ratio of the serum concentrations of MCACs to long-chain ACs (LCACs) was significantly higher during the HPA diet. Thus, direct measurement of PA OX did not confirm that the HPA diet caused incomplete PA OX, despite the modest, but statistically significant, increase in the ratio of MCACs to LCACs in blood., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

This study used mice with muscle-specific overexpression of PGC-1α, a transcriptional coactivator that promotes mitochondrial biogenesis, to determine whether increased oxidative potential facilitates metabolic improvements in response to lifestyle modification. MCK-PGC1α mice and nontransgenic (NT) littermates were fed a high-fat diet (HFD) for 10 weeks, followed by stepwise exposures to voluntary wheel running (HFD+Ex) and then 25% caloric restriction with exercise (Ex/CR), each for an additional 10 weeks with continued HFD. Running and CR improved weight and glucose control similarly in MCK-PGC1α and NT mice. Sedentary MCK-PGC1α mice were more susceptible to diet-induced glucose intolerance, and insulin action measured in isolated skeletal muscles remained lower in the transgenic compared with the NT group, even after Ex/CR. Comprehensive profiling of >200 metabolites and lipid intermediates revealed dramatic group-specific responses to the intervention but did not produce a lead candidate that tracked with changes in glucose tolerance irrespective of genotype. Instead, principal components analysis identified a chemically diverse metabolite cluster that correlated with multiple measures of insulin responsiveness. These findings challenge the notion that increased oxidative capacity defends whole-body energy homeostasis and suggest that the interplay between mitochondrial performance, lipotoxicity, and insulin action is more complex than previously proposed., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Epidemiologic evidence has suggested that diets with a high ratio of palmitic acid (PA) to oleic acid (OA) increase risk of cardiovascular disease (CVD)., Objective: To gain additional insights into the relative effect of dietary fatty acids and their metabolism on CVD risk, we sought to identify a metabolomic signature that tracks with diet-induced changes in blood lipid concentrations and whole-body fat oxidation., Design: We applied comprehensive metabolomic profiling tools to biological specimens collected from 18 healthy adults enrolled in a crossover trial that compared a 3-wk high-palmitic acid (HPA) with a low-palmitic acid and high-oleic acid (HOA) diet., Results: A principal components analysis of the data set including 329 variables measured in 15 subjects in the fasted state identified one factor, the principal components analysis factor in the fasted state (PCF1-Fasted), which was heavily weighted by the PA:OA ratio of serum and muscle lipids, that was affected by diet (P < 0.0001; HPA greater than HOA). One other factor, the additional principal components analysis factor in the fasted state (PCF2-Fasted), reflected a wide range of acylcarnitines and was affected by diet in women only (P = 0.0198; HPA greater than HOA). HOA lowered the ratio of serum low-density lipoprotein to high-density lipoprotein (LDL:HDL) in men and women, and adjustment for the PCF1-Fasted abolished the effect. In women only, adjustment for the PCF2-Fasted eliminated the HOA-diet effect on serum total- and LDL-cholesterol concentrations. The respiratory exchange ratio in the fasted state was lower with the HPA diet (P = 0.04), and the diet effect was eliminated after adjustment for the PCF1-Fasted. The messenger RNA expression of the cholesterol regulatory gene insulin-induced gene-1 was higher with the HOA diet (P = 0.008)., Conclusions: These results suggest that replacing dietary PA with OA reduces the blood LDL concentration and whole-body fat oxidation by modifying the saturation index of circulating and tissue lipids. In women, these effects are also associated with a higher production and accumulation of acylcarnitines, possibly reflecting a shift in fat catabolism.

Relative to diets enriched in palmitic acid (PA), diets rich in oleic acid (OA) are associated with reduced risk of type 2 diabetes. To gain insight into mechanisms underlying these observations, we applied comprehensive lipidomic profiling to specimens collected from healthy adults enrolled in a randomized, crossover trial comparing a high-PA diet to a low-PA/high-OA (HOA) diet. Effects on insulin sensitivity (SI) and disposition index (DI) were assessed by intravenous glucose tolerance testing. In women, but not men, SI and DI were higher during HOA. The effect of HOA on SI correlated positively with physical fitness upon enrollment. Principal components analysis of either fasted or fed-state metabolites identified one factor affected by diet and heavily weighted by the PA/OA ratio of serum and muscle lipids. In women, this factor correlated inversely with SI in the fasted and fed states. Medium-chain acylcarnitines emerged as strong negative correlates of SI, and the HOA diet was accompanied by lower serum and muscle ceramide concentrations and reductions in molecular biomarkers of inflammatory and oxidative stress. This study provides evidence that the dietary PA/OA ratio impacts diabetes risk in women.

Background: The Western diet increases risk of metabolic disease., Objective: We determined whether lowering the ratio of saturated fatty acids to monounsaturated fatty acids in the Western diet would affect physical activity and energy expenditure., Design: With the use of a balanced design, 2 cohorts of 18 and 14 young adults were enrolled in separate randomized, double-masked, crossover trials that compared a 3-wk high-palmitic acid diet (HPA; similar to the Western diet fat composition) to a low-palmitic acid and high-oleic acid diet (HOA; similar to the Mediterranean diet fat composition). All foods were provided by the investigators, and the palmitic acid (PA):oleic acid (OA) ratio was manipulated by adding different oil blends to the same foods. In both cohorts, we assessed physical activity (monitored continuously by using accelerometry) and resting energy expenditure (REE). To gain insight into a possible mood disturbance that might explain changes in physical activity, the Profile of Mood States (POMS) was administered in cohort 2., Results: Physical activity was higher during the HOA than during the HPA in 15 of 17 subjects in cohort 1 (P = 0.008) (mean: 12% higher; P = 0.003) and in 12 of 12 subjects in the second, confirmatory cohort (P = 0.005) (mean: 15% higher; P = 0.003). When the HOA was compared with the HPA, REE measured during the fed state was 3% higher for cohort 1 (P < 0.01), and REE was 4.5% higher in the fasted state for cohort 2 (P = 0.04). POMS testing showed that the anger-hostility score was significantly higher during the HPA (P = 0.007)., Conclusions: The replacement of dietary PA with OA was associated with increased physical activity and REE and less anger. Besides presumed effects on mitochondrial function (increased REE), the dietary PA:OA ratio appears to affect behavior. The second cohort was derived from a study that was registered at clinicaltrials.gov as R01DK082803.

Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who are exquisitely insulin sensitive. Understanding the molecular mechanisms that mediate the expansion and appropriate metabolic control of LDs in the context of habitual physical activity could lead to new therapeutic opportunities. Herein, we show that acute exercise elicits robust upregulation of a broad program of genes involved in regulating LD assembly, morphology, localization, and mobilization. Prominent among these was perilipin-5, a scaffolding protein that affects the spatial and metabolic interactions between LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and primary human skeletal myocytes established a key role for the exercise-responsive transcriptional coactivator PGC-1α in coordinating intramuscular LD programming with mitochondrial remodeling. Moreover, translational studies comparing physically active versus inactive humans identified a remarkably strong association between expression of intramuscular LD genes and enhanced insulin action in exercise-trained subjects. These results reveal an intimate molecular connection between intramuscular LD biology and mitochondrial metabolism that could prove relevant to the etiology and treatment of insulin resistance and other disorders of lipid imbalance.

Objective: Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines. This investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism., Research Design and Methods: Interactions between these two tissues were modeled using a coculture system composed of primary human adipocytes and human skeletal myotubes derived from lean or obese donors. Metabolic analysis of myocytes was performed after coculture with lipolytically silent or activated adipocytes and included transcript and metabolite profiling along with assessment of substrate selection and insulin action., Results: Cocultured adipocytes increased myotube mRNA expression of genes involved in oxidative metabolism, regardless of the donor and degree of lipolytic activity. Adipocytes in the basal state sequestered free fatty acids, thereby forcing neighboring myotubes to rely more heavily on glucose fuel. Under this condition, insulin action was enhanced in myotubes from lean but not obese donors. In contrast, when exposed to lipolytically active adipocytes, cocultured myotubes shifted substrate use in favor of fatty acids, which was accompanied by intracellular accumulation of triacylglycerol and even-chain acylcarnitines, decreased glucose oxidation, and modest attenuation of insulin signaling., Conclusions: The effects of cocultured adipocytes on myocyte substrate selection and insulin action depended on the metabolic state of the system. These findings are relevant to understanding the metabolic consequences of intermuscular adipogenesis., (© 2011 by the American Diabetes Association.)

In cultured cells, palmitic acid (PA) and oleic acid (OA) confer distinct metabolic effects, yet, unclear, is whether changes in dietary fat intake impact cellular fatty acid (FA) composition. We hypothesized that short-term increases in dietary PA or OA would result in corresponding changes in the FA composition of skeletal muscle diacylglycerol (DAG) and triacylglycerol (TAG) and/or the specific FA selected for β-oxidation. Healthy males (N = 12) and females (N = 12) ingested a low-PA diet for 7 days. After fasting measurements of the serum acylcarnitine (AC) profile, subjects were randomized to either high-PA (HI PA) or low-PA/high-OA (HI OA) diets. After 7 days, the fasting AC measurement was repeated and a muscle/fat biopsy obtained. FA composition of intramyocellular DAG and TAG and serum AC was measured. HI PA increased, whereas HI OA decreased, serum concentration of 16:0 AC (P < 0.001). HI OA increased 18:1 AC (P = 0.005). HI PA was associated with a higher PA/OA ratio in muscle DAG and TAG (DAG: 1.03 ± 0.24 vs. 0.46 ± 0.08, P = 0.04; TAG: 0.63 ± 0.07 vs. 0.41 ± 0.03, P = 0.01). The PA concentration in the adipose tissue DAG (µg/mg adipose tissue) was 0.17 ± 0.02 in those receiving the HI PA diet (n = 6), compared to 0.11 ± 0.02 in the HI OA group (n = 4) (P = 0.067). The relative PA concentration in muscle DAG and TAG and the serum palmitoylcarnitine concentration was higher in those fed the high-PA diet.

In humans, insulin sensitivity is relatively impaired by diets that are low in oleic acid (OA), a cis monounsaturated fatty acid (MUFA), or rich in trans MUFA or palmitic acid (PA), a saturated fatty acid (FA). Emerging evidence exists that PA, in contrast to OA, causes insulin resistance via stimulation of inflammatory signaling and production of cytosolic lipid compounds (diacylglycerol and ceramide), leading one to presume that dietary or pharmacologic maneuvers that facilitate transport of FA into the mitochondria would be beneficial. However, in some models, insulin resistance is caused by excessive FA transport into the mitochondria, coupled with deficient electron transport and possibly increased reactive oxygen species formation; PA may impair electron transport via effects on gene expression. A research challenge is to determine whether feeding humans diets with markedly different contents of PA and OA would alter insulin sensitivity and/or critical biochemical mechanisms impacting muscle insulin signaling.

Background: Cecal or distal colonic concentration of butyrate has been used as an index of butyrate production from various fermentable carbohydrates. However, we previously found that cecal concentration of butyrate does not correlate with the rate of synthesis of butyrate in the cecal lumen. As part of a larger study of the cellular effects of cecal infusions of butyrate, we sought to rule out the null hypothesis that cecal infusion of butyrate also would not alter butyrate concentration in the cecum., Methods: Piglets (n = 10) were fed sow milk replacement formula plus inulin (3 g x L(-1)). After 6 days of oral feeding, the piglets were randomly assigned into 2 equal groups: (I) Cecal infusion of phosphate-buffered NaCl and (II) cecal infusion of butyrate (2.13 micromol x kg(-1) x min(-1)). The concentration of butyrate was measured by gas chromatography in the cecum and distal colon., Results: There was no effect of cecal butyrate infusion on butyrate concentration (mM; I vs II) in the cecum (5.7 +/- 0.4 vs 5.3 +/- 1.1) or distal colon (3.3 +/- 0.6 vs 4.1 +/- 0.8) or on the ratio of cecal butyrate concentration to the sum of the concentrations of butyrate, acetate, propionate, and valerate (0.101 +/- 0.004 vs 0.083 +/- 0.011). There was no effect of cecal butyrate infusion on the concentration of any of these short chain fatty acids., Conclusions: At an entry rate into the cecum within the physiological range, butyrate had no effect on cecal or distal colonic luminal concentration of butyrate.

Objective: Because estrogen and testosterone affect transcription factors regulating mitochondrial function, we assessed the effects of gender on the metabolic response to dietary palmitic acid (PA) vs. oleic acid (OA) in subjects participating in a previously described trial., Methods and Procedures: Adults (N = 43) were studied after following a baseline diet (PA = 8.4% kcal, OA = 13.1% kcal) and after undergoing one of two experimental diets: high PA (HI PA) (PA = 16.8%, OA = 16.4% kcal) (N = 21; 11 men) or high OA (HI OA) (PA = 1.7%, and OA = 31.4%) (N = 22; 11 men)., Results: Relative to baseline, the rate of fatty acid (FA) oxidation (% resting energy expenditure(REE)) (mean +/- s.e.m.) increased in women on HI OA while decreasing on HI PA in the fed (+11.8 +/- 5.6% vs. -6.3 +/- 4.2%, P = 0.02) and fasting states (+13.4 +/- 4.2% vs. -12.7 +/- 6.9%, P = 0.047), but changes in men were not statistically significant. Daily energy expenditure changed only in men, increasing on HI OA and decreasing on HI PA (+66 +/- 61 kcal/day or 1.2 +/- 1.0 kcal/kg fat-free mass (FFM)/day vs. -266 +/- 78 kcal/day or -4.2 +/- 1.3 kcal/kg FFM/day, P = 0.004 and P = 0.007, respectively)., Discussion: Increased dietary PA/OA caused decreased FA oxidation in women, in the fed and fasted states and decreased daily energy expenditure (DEE) in men.

Objective: Using tracers, we showed, over 9 hours, that palmitic acid (PA) is oxidized at a lower rate than oleic acid (OA). Our subsequent clinical trial showed that enriching the diet for 28 days with PA, relative to OA, lowered fatty acid (FA) oxidation. However, because this conclusion was based on indirect calorimetry for 7 hours after a test meal, transient differences in the kinetics of oxidation of OA and PA could explain these results. Thus, we hypothesized that increasing PA vs. OA would decrease FA oxidation during the first day of feeding the diets., Research Methods and Procedures: A double-masked trial was conducted in 20 adults, who, after a baseline diet, were randomized to one of two experimental formula diets: high (HI) OA (PA=1.7% kcal, OA=31.4% kcal; N=11) or HI PA (PA=16.8% kcal, OA=16.4% kcal; N=9). Respiratory quotient (RQ) was measured over the first 14 hours of feeding the experimental diets (7:00 am to 9:00 pm). To determine whether these subjects were representative of the subjects in the previous trial, we assessed RQ 28 days after beginning either diet., Results: During the first 14 hours of feeding the diets, time (p=0.026) but not diet group had an effect on the difference between the RQ post-feeding and the fasting pre-value. However, RQ in the fed state was significantly higher in the HI PA group after 28 days of feeding., Discussion: Chronically increasing dietary PA for 28 days, but not acute meal feeding, lowers total FA oxidation.

Background: In order to understand the consequences of persistent enteral feeding in patients with carbohydrate malabsorption, we fed piglets lactulose in sufficient dosage to produce osmotic diarrhea or inulin, using a conventional dose, to determine if this prebiotic can modulate the effects of lactulose. Feeding lactulose increases cecal luminal synthesis of butyrate, with inulin having an intermediate effect. Because clostridia may be a major source of colonic butyrate production, we hypothesized that feeding piglets lactulose or inulin would increase cecal densities of clostridia., Methods: Piglets were assigned to 3 formula study groups for 6 days: (1) control, fed only sow milk replacer (n = 12); (2) inulin, inulin supplement (3 g/L; n = 11); and (3) lactulose, lactulose supplement (66.7 g/L; n = 6). Cecal fluid for bacteriological studies was sampled intraoperatively., Results: The wet/dry ratio of the cecal contents (mean +/- SEM) was 8.2 +/- 0.5, 6.2 +/- 0.5, and 18.8 +/- 5.5, respectively, in the control, inulin, and lactulose groups (p = .049, Kruskal-Wallis). There were no differences among the diet groups for cecal densities (10(6) colony-forming units [CFU]/g dry wt cecal contents) of total anaerobes, total aerobes, bifidobacteria, or lactobacilli. Densities of clostridia were markedly reduced in the lactulose group (1.14 +/- 0.41) vs the control (18.39 +/- 4.44; p = .001) or inulin groups (8.87 +/- 2.20; p = .04)., Conclusions: In piglets, feeding lactulose at a dose known to cause diarrhea reduces cecal densities of clostridia.

The effects of colon-derived butyrate on intestinal cell proliferation are controversial. In vitro studies suggest an inhibitory effect, and in vivo studies suggest the opposite, but neither type of study has been based on a physiologically relevant, intracolonic supply of butyrate. In this study, piglets (n = 24) were fed sow's milk replacement formula and randomized into 4 equal groups: 1) control; 2) cecal butyrate infusion at a rate equal to that produced in the colon; 3) inulin supplementation at a concentration previously found to lower cecal cell proliferation; and 4) butyrate infusion plus inulin supplementation. After 6 d of oral feeding, cecal butyrate infusions were initiated for a period of 4 d. Cecal, distal colonic, jejunal, and ileal cell proliferation, apoptosis, and morphology were evaluated and serum concentration of glucagon-like peptide-2 (GLP-2) was measured. Butyrate or inulin did not affect GLP-2, weight gain, apoptosis, intestinal injury scores, cecal or colon crypt depth, and jejunal or ileal villus height. For cell proliferation, there was a significant interaction between inulin, butyrate, and tissue (P = 0.007). Inulin modified the effect of butyrate (butyrate x inulin interaction in cecum, P = 0.001; in distal colon, P = 0.018; in ileum, P = 0.001; and in jejunum, P = 0.003). In the absence of inulin, butyrate caused a 78- 119% increase in cell proliferation in the ileum, distal colon, jejunum, and cecum (P < or = 0.002). Thus, at an entry rate into the colon within the physiological range, butyrate caused increased intestinal cell proliferation, but inulin tended to block this effect. Thus, intracolonic butyrate may enhance intestinal growth during infancy.

Our previous studies suggest that diets varying in palmitic acid (PA) and oleic acid (OA) content may affect energy expenditure and fat oxidation differentially. We hypothesized that, compared with a high-OA diet, a high-PA diet would lead to lower oxygen consumption during exercise and lower excess postexercise oxygen consumption (EPOC). Adults were randomized to 1 of 2 liquid diets (28 days): HI PA (fat, 40% of energy; PA, 16.8%; OA, 16.4%) (n = 10) or HI OA (fat, 40%; PA, 1.7%; OA, 31.4%) (n = 9). On day 29, the rates of oxygen consumption (V o(2)) and carbon dioxide production were measured during and for 270 minutes after 80 minutes of cycling (60% V o(2 peak)). There was no group difference (HI OA vs HI PA, mean +/- SEM) in fat-free mass (53.8 +/- 4.7 vs 56.9 +/- 3.0 kg), V o(2 peak) (40.7 +/- 2.3 vs 36.6 +/- 3.2 mL/kg per minute), and work during exercise (101 +/- 12 vs 101 +/- 10 W). V o(2) (L/min) during exercise (1.99 +/- 0.22 vs 1.85 +/- 0.19) was significantly different (P = .05) only when corrected for fat-free mass, with which it significantly correlated (r = 0.86; P < .001). During 60 to 270 minutes postexercise, the average EPOC was 9.7% +/- 4.9% of preexercise V o(2) in OA, whereas there was no EPOC present in PA (P = .06 between diets). In conclusion, a high-PA diet appears to lower V o(2) during and after exercise compared with a high-OA diet.

Butyrate inhibits colonic cell proliferation in vitro but reportedly has an opposite effect in vivo. Because lactulose feeding decreases cecal cell proliferation, an effect attenuated by prefeeding inulin, we hypothesized that lactulose feeding would decrease colonic luminal synthesis of butyrate, and that prefeeding and cofeeding inulin would prevent this effect. Piglets (n = 31) were catheterized and randomly assigned to 1 of 4 groups: Control formula (C); control formula + lactulose (L); control formula + lactulose + inulin (L + I); and control formula + inulin (I). At 6 and 7 d postsurgery, the rate of cecal synthesis of butyrate, cecal cell proliferation and apoptosis, and cecal and distal colon butyrate concentration were measured. In groups C, L, L + I, and I, the rates of synthesis of butyrate (mean +/- SEM) were 10.6 +/- 3.2, 23.3 +/- 4.5, 12.4 +/- 3.6, and 14.6 +/- 4.0 micromol/min, respectively (Group Effect, P = 0.1; C vs. L, P = 0.03; L vs. L + I, P = 0.06). The cecal butyrate concentrations did not differ among the 4 groups and were 8.7 +/- 3.2, 2.4 +/- 0.8, 3.4 +/- 1.9, and 2.0 +/- 0.7 micromol/g dry wt, respectively. The total cecal cell proliferation index was higher in C than in L (P = 0.008) or I (P = 0.026) and was higher in L + I than in L (P = 0.013) or I (P = 0.046). The increased supply of butyrate to the cecum was associated with decreased cell proliferation, but cecal butyrate concentration did not reflect synthesis.

Background: Diarrhea is a common problem in critically ill patients. Our patients are fed a high-carbohydrate enteral formula. We hypothesized that diarrhea in our patients may be related to the osmotic effects of unabsorbed carbohydrate in the small intestine and colon., Methods: We studied 19 patients, 3 months to 17 years, with burns >40% total body surface area. Each subject was studied weekly for up to 4 weeks postburn. Breath H2 concentration was measured. For the 24-hour period before the breath H2 measurement, the enteral carbohydrate intake, stool volume, and total enteral fluid volume were recorded. At each of several weekly intervals for each subject, the times when stool volume and enteral carbohydrate intake were each maximal were noted., Results: Maximal stool volume ranged from 12 to 69 mL/kg/d. At the time point of maximal carbohydrate intake, diarrhea (stool volume >10 mL/kg/d) occurred in 18 of 19 patients, and maximal stool volume occurred in 10 of 19. Breath H2 concentration (ppm/5% CO2; mean +/- SEM) was 5.5 +/- 3.5 at the time of maximal carbohydrate intake, and was 25 +/- 20 at maximal stool volume. There were no correlations among breath H2 concentration, stool volume, enteral fluid intake, and enteral carbohydrate intake., Conclusions: Almost all the subjects had diarrhea over several weeks postburn. The lack of correlation of either carbohydrate intake or breath H2 with stool volume suggests that diarrhea in these patients may be caused by factors other than carbohydrate malabsorption. These data do not support altering nutrition support because of watery diarrhea.

Background: During feeding trials, it is useful to predict daily energy expenditure (DEE) to estimate energy requirements and to assess subject compliance., Objective: We examined predictors of DEE during a feeding trial conducted in a clinical research center., Design: During a 28-d period, all food consumed by 26 healthy, nonobese, young adults was provided by the investigators. Energy intake was adjusted to maintain constant body weight. Before and after this period, fat-free mass (FFM) and fat mass were assessed by using dual-energy X-ray absorptiometry, and DEE was estimated from the change (after - before) in body energy (DeltaBE) and in observed energy intake (EI): DEE = EI - DeltaBE. We examined the relation of DEE to pretrial resting energy expenditure (REE), FFM, REE derived from the average of REE and calculated from FFM [REE = (21.2 x FFM) + 415], and an estimate of DEE based on the Harris-Benedict equation (HB estimate) (DEE = 1.6 REE)., Results: DEE correlated (P < 0.001) with FFM (r = 0.78), REE (r = 0.73), average REE (r = 0.82), and the HB estimate (r = 0.81). In a multiple regression model containing all these variables, R(2) was 0.70. The mean (+/-SEM) ratios of DEE to REE, to average REE, and to the HB estimate were 1.86 +/- 0.06, 1.79 +/- 0.04, and 1.02 +/- 0.02, respectively., Conclusions: Although a slightly improved prediction of DEE is possible with multiple measurements, each of these measurements suggests that DEE equals 1.60-1.86 x REE. The findings are similar to those of previous studies that describe the relation of REE to DEE measured directly.

Objectives: Severe lactulose malabsorption causes osmotic diarrhea and decreased cecal cell proliferation. We tested the hypothesis that prefeeding with inulin, a prebiotic, would attenuate these effects., Methods: Piglets aged 10 days were randomized to 3 feeding groups (n = 6 each group): Control (CON), fed sow-milk replacement formula (SMR; lactose, 60 g/L) for 14 days; a lactulose-challenged group (LAC) that was fed SMR for 7 days and then a formula containing lactose (30 g/L) and lactulose (60 g/L) for 7 days; and a group prefed SMR containing inulin (3 g/L) for 7 days and then fed the lactulose-supplemented formula (INULIN). Groups CON and INULIN were pair-fed to LAC. Then, cecal tissue was collected for histology, determination of crypt cell proliferation index, apoptosis, and Western blot determination of expression of Bax, a pro-apoptotic protein., Results: The fraction of days when diarrhea was present (mean +/- SD) was greater for LAC (0.87 +/- 0.14; p = .004) than CON (0.28 +/- 0.22; INULIN: 0.52 +/- 0.44; p = .058 vs LAC). Cell proliferation index for the total crypt was less for LAC (0.12 +/- 0.04; p = .016) compared with CON (0.20 +/- 0.04; INULIN: 0.15 +/- 0.04; p = .06 vs LAC). BAX protein expression and apoptosis were similar in the 3 groups., Conclusions: We observed trends consistent with the hypothesis that prefeeding inulin attenuates diarrhea and the reduction in cell proliferation caused by lactulose.

Background: Intestinal malabsorption of disaccharides or oligosaccharides occurs normally in preterm infants, the majority of the world's adult population when ingesting dairy products, and in sick patients with abnormal intestinal motility or intestinal damage. Although there may be benefit to colonic fermentation, there also could be mucosal damage from excessive fermentation. Moreover, excess fluid in the colon also may impair fermentation. There are few data that address the effects of moderate amounts of carbohydrate, such as 50% of intake, reaching the colon. We addressed the hypothesis that normal weight gain and stool characteristics would occur during disaccharide malabsorption approximating 50% of intake., Methods: Twelve piglets (aged 17 days) were randomized to receive control sow milk replacement formula (CON; lactose 60 g/L) or CON modified so that lactulose replaced 50% of the lactose (LAC). During a 5- to 7-day period, weight gain and fecal characteristics were observed before autopsy for cecal histology and determination of cecal cell proliferation using bromodeoxyuridine., Results: Neither group developed diarrhea. In LAC and CON, formula intakes (g/kg/d) were similar (279 +/- 30 and 280 +/- 35), as were the ratios of weight gain:formula intake (g/mL): 0.23 +/- 0.04 and 0.22 +/- 0.04. Mean cecal cell proliferation was not diminished in the group receiving lactulose (p > .05)., Conclusion: These data suggest that moderate (50%) disaccharide malabsorption per se does not cause diarrhea and does not impair dietary energy use or colonic cell proliferation.

Objectives: Butyric acid, synthesized via bacterial fermentation in colonic lumen, may play an important role in the nutrition of the colonic mucosa. Since disaccharides, especially lactose, are the principal dietary carbohydrates during infancy, it is important to determine if their fermentation is associated with butyric acid synthesis. The objective of this paper is to describe a newly developed stable isotope method for quantifying butyric acid synthesis in the colonic lumen and to demonstrate its application during cecal infusions of lactose and lactulose in piglets., Methods: Nine piglets aged 21 to 30 days were studied during acute anesthesia. The C enrichment of butyric acid was monitored in the portal vein before and during a 120 minutes cecal infusion of [1- C]-butyric acid and either unlabeled lactose (N = 4) or lactulose (N = 5)., Results: The luminal synthesis of BA (micromol x kg x min ) (Mean +/- S.D.) was respectively 1.5 +/- 0.9 and 1.2 +/- 0.6 during lactulose and lactose infusion., Conclusions: This study provides new quantitative data on in vivo butyric acid production in the mammalian colon.

Most symptomatic patients with biotinidase deficiency have both neurologic and cutaneous symptoms and typical organic aciduria. We encountered a previously healthy girl with complete biotinidase deficiency presenting initially at age 17 months with episodic ataxia that became severe progressive ataxia in 2 months, but without skin rash or typical organic aciduria, which resolved completely with biotin treatment. Additionally, moderate sensorineural deafness also improved to the normal range. Even without typical cutaneous findings or organic aciduria, biotinidase deficiency should be considered among the differential diagnosis in any child presenting with either episodic or progressive ataxia or sensorineural deafness as prompt diagnosis and treatment with biotin may induce an excellent recovery.

We hypothesized that there is no synthesis of butyric acid within organs or tissues not drained by the portal vein (PV). Two experiments were performed. In six piglets, the colonic vasculature was clamped (n = 4) or the entire colon resected while [1-13C]-butyric acid (99% enriched) was infused into a jejunal vein for 120 min; 13C enrichment of butyric acid was measured in the PV and carotid artery (ART) during the last 30 min of the infusion. In a second experiment, butyric acid tracer and unlabeled disaccharide were infused into the cecum for 120 min, and blood again was sampled from the PV and ART. For the four piglets studied during ligation of the colonic vasculature, the mean (+/- SD) ratio of the butyric acid enrichment in the ART to that in the PV (ART/PV) was 0.80+/-0.05 (ART vs. PV, P = 0.002) and for all six piglets in expt. 1, the ART/PV ratio was 0.74+/-0.1 (ART vs. PV, P = 0.001). The enrichment of butyric acid in the PV averaged 96.0% for the six studies, implying that splanchnic tissues other than the colon did not produce a substantial amount of butyric acid. For the second experiment, the ART/PV ratio was 0.80+/-0.15 (ART vs. PV, P = 0.03). These studies provide the first evidence for endogenous synthesis of butyric acid by piglets.

Differences in oxidation of individual dietary fatty acids could contribute to the effect of dietary fat composition on risk factors for non-insulin-dependent diabetes mellitus and cardiovascular disease. Using a novel stable isotope technique, we compared fractional oxidation of chylomicron-derived oleate and palmitate in 10 healthy adults in a crossover study. 1-(13)C-labeled oleate or palmitate was emulsified into a eucaloric formula diet administered each 20 min for 7 h to produce a plateau in excretion of (13)C label in breath CO(2). Unlabeled oleate and palmitate each provided 16% of dietary energy, and other fatty acids provided 8% of energy. Total dietary fat was 40% of energy, carbohydrate was 46%, and protein was 14%. Diet without tracer was fed for 2 h before beginning tracer administration to establish a baseline fed state. Relative oxidation of oleate versus palmitate was defined as fractional oxidation of oleate divided by fractional oxidation of palmitate. Relative oxidation averaged 1.21 (99.5% confidence interval = 1.03;-1.39), indicating that fractional oxidation of oleate was significantly greater than that of palmitate.

We sought to determine, in a piglet model, whether severe sugar malabsorption causes colonic injury or inflammation. Twenty-four piglets were randomized to receive either control formula (CON) or CON supplemented with lactulose (LAC) (N = 12 each group). After seven days, inflammation, apoptosis, and crypt cell proliferation were assessed in the proximal colon (cecum). Lactulose feeding caused persistent diarrhea. In both groups, breath H2 concentration was low, suggesting no increased fermentation in the LAC group. Weight gain/volume formula intake was identical in the CON and LAC groups (0.09+/-0.13 and 0.09+/-0.11 g/ml) respectively. Injury to the colon did not occur, but inflammation of the colon (scale 0-5) was greater in LAC (score of 1.5+/-1.38) than in CON (0.42+/-0.79; P<0.05). Cell proliferation at the basal 40% of the crypt was 92% increased in CON (labeling index 22.8+/-9.9 vs. 11.9+/-2.8; P<0.05). We conclude that persistent feeding during severe sugar malabsorption permits weight gain but may cause colitis.

Interpretation of tracer studies of amino acid kinetics in the fed state is dependent on knowledge of splanchnic uptake of diet-derived amino acids. We studied five healthy control children and five children with cystic fibrosis (CF). After an overnight fast, the children ingested, hourly, a formula diet for 11 h. 5,5,5-[2H3]Leucine was added to the feedings during the last 6 h, and an i.v. infusion of 1-[13C]leucine was administered during the last 2 h of the formula feeding. The mean rate of splanchnic uptake of leucine was similar in the CF and control group, 23.8 +/- 24.0 and 21.5 +/- 21.2 mumol.kg-1.h-1, respectively. Fractional splanchnic uptake of leucine was not significantly different in the patients with CF (0.16 +/- 0.112 mean +/- SD) compared with the control children (0.244 +/- 0.256(-1)). The rate of whole body protein breakdown was not significantly different between the groups (CF versus control) with (159 +/- 18 versus 135 +/- 28 mumol.kg-1.h-1) or without (135 +/- 14 versus 114 +/- 20 mumol.kg-1.h-1) correction for splanchnic leucine uptake. However, for the 10 cases combined, protein breakdown corrected for splanchnic leucine uptake (147 +/- 26 mumol.kg-1.h-1) was 18% greater than uncorrected protein breakdown (124 +/- 20 mumol.kg-1.h-1) (p = 0.009). The data suggest that companion studies of splanchnic uptake might enhance the interpretation of leucine kinetics in the fed state.

Background: The authors have previously demonstrated abnormalities in glucose and insulin metabolism in nondiabetic black American (BA) adults versus white American (WA) adults. Whether similar glucoregulatory alterations extend to BA adolescents remain unknown. In addition, obesity, a known risk factor for insulin resistance and hyperinsulinemia, occurs in a greater proportion of BA adults and children when compared to WA. The objective of the present study was to examine the differential effects of obesity on glucose homeostasis in BA and WA adolescents., Methods: We examined glucose homeostasis in BA and WA adolescents using oral glucose tolerance test (OGTT), intravenous glucose tolerance test (IVGTT), and [6,6-2H2]-glucose infusion. The study consisted of four age-, sex-, and pubertal stage-matched groups: 15 lean BA, 29 lean WA, 7 obese BA, and 9 obese WA., Results: Both obese groups had significantly increased insulin and C-peptide area under the curve (AUC) during OGTT and IVGTT when compared to their same-race lean counterparts. During OGTT, obese BA demonstrated greater insulin and C-peptide when compared to obese WA. During IVGTT, first- and second-phase insulin were significantly greater in obese BA versus obese WA., Conclusion: In summary, BA adolescents demonstrated insulin resistance which is markedly exaggerated in the face of obesity when compared to WA adolescents, implying a differential impact for obesity on glucose homeostasis that is unique to the obese BA adolescent group. In conclusion, there is a need for early aggressive weight management in obese BA adolescents.

The purpose of this study was to determine whether doubling the lactose concentration in formula for preterm infants lowers the fraction of lactose digested and/or increases the fraction of lactose fermented. Six preterm infants, 31 to 36 weeks' postconceptional age, were fed a standard preterm formula (carbohydrate is 50% lactose and 50% glucose polymer)(SC) and/or the same volume of formula modified to contain lactose as the sole carbohydrate (LAC). Relative lactose digestion during the LAC formula feeding compared with SC formula feeding was measured by using a stable isotope approach for quantifying the fractional contribution of formula lactose to plasma glucose enrichment. Relative lactose digestion was 0.98 +/- 0.17 (range, 0.70 to 1.19). Fractional fermentation of lactose was estimated from breath H2 excretion (0.52 +/- 0.34 during LAC feeding and 0.23 +/- 0.22 during SC feeding, P = .11). The rate of breath H2 excretion was much higher with LAC (1.34 +/- 0.98 mL/h) than with SC (0.27 +/- 0.29, P = .029). In conclusion, doubling the lactose concentration had only modest effects on fractional lactose digestion. Increased breath H2 excretion with LAC may relate to fermentation of nonlactose sugar or to ill-defined changes in colonic physiology or motility, which could enhance colonic fermentation of malabsorbed sugar by H2-producing bacteria.