Anthropometric correlates of lipoprotein profile and blood pressure in high BMI African American children.

OBJECTIVE: To explore the association of anthropometric indices with lipoprotein profile and blood pressure as risk factors of cardiovascular disease, in African American (AA) children. METHODS: A cross-sectional analysis was carried out on children aged 9-13 years with BMI >85th percentile. Height, weight, waist and hip circumferences, % body fat and blood pressure [systolic (sBP) and diastolic (dBP)] were measured. Fasting plasma levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), intermediate density lipoprotein cholesterol (IDL-C) and very low-density lipoprotein cholesterol (VLDL-C) were analysed. RESULTS: After accounting for age, gender and pubertal status of the child, multiple linear regression models showed that waist circumference and BMIz were strong predictors for lipoprotein variables. In independent analysis, waist circumference and BMI z-scores were found to be interdependently associated with TG, LDL-C:HDL-C ratio, VLDL-C and sBPz. However, for HDL-C, TG:HDL-C ratio and dBPz, waist circumference was independently and more strongly associated with these risk factors than BMI. CONCLUSION: Waist circumference was a stronger predictor for lipoprotein variables and blood pressure in high BMI AA children than other anthropometric indices, and may be adequate as a screening test to identify children who are at increased risk for cardiovascular disease.

Absorption and metabolism of octanoate by the rat colon in vivo: concentration dependency and influence of alternative fuels.

BACKGROUND: Compared with short and long chain fatty acids, medium chain fatty acids (MCFAs) have been shown to provide the highest colonic absorption of substrate carbon. Moreover, colonic epithelial cells fulfil their basic energy requirements as easily from MCFAs as from short chain fatty acids. AIMS: To further characterise octanoate as a colonic luminal substrate, we determined in vivo the influence of (i) substrate concentration and (ii) alternative luminal fuels, on rat colonic transport and metabolism. METHODS: Segments of rat proximal colon (8 cm) were cannulated and perfused for 100 min with (14)C labelled octanoate. The right colic vein was also cannulated and venous blood analysed for total (14)C, (14)CO(2), and metabolites by scintillation counting and high performance liquid chromatography. RESULTS: Tracer appearance in mesenteric blood stabilised after 20-40 minutes of perfusion. Increasing luminal octanoate concentrations from 2 to 40 mM resulted in linear increases in total carbon absorption. Maximum CO(2) production was reached near 10 mM. A substantial proportion of octanoate was absorbed without being metabolised (59-94%). The luminal presence of a mixture of alternative fuels had no influence on either octanoate transport or metabolism. CONCLUSIONS: This study demonstrated substantial concentration dependent colonic absorption of octanoate, rendering this MCFA a potential and much needed high energy substrate for patients with compromised small bowel function. Moreover, octanoate meets the basic energy requirements of colonic epithelial cells in vivo as well as butyrate. This study also demonstrates the divergence of in vitro and in vivo data regarding fatty acid absorption and metabolism in the colonic epithelium.

In vivo absorption of medium-chain fatty acids by the rat colon exceeds that of short-chain fatty acids.

BACKGROUND AND AIMS: Short-chain fatty acids (SCFAs) are main fuels of the colonic epithelium, and are avidly absorbed by the colon of animal and man. The current knowledge on colonic metabolism and absorption of medium-chain fatty acids (MCFAs) is limited. In some clinical situations, colonic absorption of high-energy substances could compensate for reduced absorptive capacity because of a shortened or malfunctioning small bowel. We evaluated and compared colonic absorption and metabolism of MCFAs (octanoate, decanoate, and dodecanoate), SCFAs (acetate and butyrate), and long-chain fatty acids (LCFAs) (oleate). METHODS: Rats were surgically operated on to cannulate a 7-cm segment of proximal colon, isolate the vasculature, and cannulate the right colic vein draining this segment. The lumen was perfused with (14)C-labeled substrates for 100 minutes. Right colic vein blood was analyzed for total (14)C, (14)CO(2), and metabolites by scintillation counting and high-performance liquid chromatography. RESULTS: The transport from the colonic lumen to mesenteric blood of substrate carbon from MCFAs exceeded by 2-13-fold that of SCFAs and LCFAs. The CO(2) production from the oxidation of MCFAs was as high as or higher than that from SCFAs. CO(2) produced from the LCFA, oleate, was lower than from SCFAs or MCFAs. In addition to CO(2), ketone bodies were major metabolites of SCFAs and MCFAs. Ketogenesis from butyrate and the MCFAs was significantly higher than from acetate and oleate. A substantial proportion (50%-90%) of all substrates was absorbed without being metabolized. CONCLUSIONS: The colonic epithelium serves to absorb and partially metabolize MCFAs. For patients with a compromised small-bowel function, colonic absorption of MCFAs could represent an important way of receiving calories.

Metabolism of short-chain fatty acids by rat colonic mucosa in vivo.

To determine the influence of substrate concentration and substrate interactions on short-chain fatty acid metabolism in vivo, a surgical procedure was established. Rats were surgically operated to cannulate a 5-cm segment of proximal colon, isolate the vasculature, and cannulate the right colic vein draining this segment. Thus metabolism was restricted to the defined colonic segment. The appearance of total (14)C and (14)CO(2) in the mesenteric blood stabilized after 30 min of perfusion. Increasing luminal concentrations of butyrate from 2 to 40 mmol/l resulted in linear increases in total (14)C, but (14)CO(2) production from [(14)C]butyrate increased as a function of concentration only up to 10 mmol/l and was stable at higher butyrate concentrations. In addition to CO(2), 3-hydroxybutyrate and lactate were major metabolites of acetate and butyrate in vivo. The presence of a mixture of alternative substrates in the lumen had no influence on the metabolism of butyrate to CO(2) but significantly reduced the metabolism of acetate to CO(2). When compared with young (4 mo old) animals, transport of butyrate was significantly lower for aged (48 mo old) animals, as evidenced by the rate of appearance in blood of total (14)C (P = 0.04) and (14)C in butyrate (P = 0.03), but metabolism was similar, since differences were not significant for (14)C in the major metabolites 3-hydroxybutyrate (P = 0.06) and CO(2) (P = 0.17). These results show that important aspects of short-chain fatty acid transport and metabolism are not predicted from data using isolated colonocytes but require study using an in vivo model.

Rate at which glutamine enters TCA cycle influences carbon atom fate in intestinal epithelial cells.

Glutamine carbon entry into the tricarboxylic acid (TCA) cycle was assessed in small intestinal epithelial cells by measuring CO2 production from [1-14C]glutamine, and these data together with [U-14C]glutamine data were used to calculate fractional oxidation rates for glutamine. CO2 production from either [1-14C]glutamine or [U-14C]glutamine showed saturation kinetics, and the concentration needed to achieve the half-maximal rate of CO2 production was 0.7 and 0.4 mmol/l, respectively. Maximal rate for [1-14C]glutamine was twice that for [U-14C]glutamine. Increasing glutamine concentration did not cause proportional increases in glutamine entry into the TCA cycle and glutamine oxidation. Consequently, fractional oxidation of glutamine decreased with increasing glutamine concentration. Fractional oxidation could be predicted from the rate at which glutamine carbon entered the TCA cycle. (Aminooxy)acetic acid, an aminotransferase inhibitor, reduced entry of glutamine into the TCA cycle and increased fractional oxidation of glutamine. Glutamate carbon entered the TCA cycle at about one-half the rate of glutamine-derived glutamate carbon and had a higher fractional oxidation rate when provided at equivalent concentrations to glutamine. These differences in the rate of entry predictably account for the differences in the metabolic fate of glutamine vs. glutamate carbon.

Glucose and glutamine provide similar proportions of energy to mucosal cells of rat small intestine.

The objectives of this study were to establish a reliable method for quantifying glycolytic flux in intestinal epithelial cells, to determine the proportion of energy provided to small intestine epithelial cells by glucose vs. glutamine, and to determine whether there was an energetic advantage to having both substrates present simultaneously. There was substantial retention of 3H in alanine and lactate when [2-(3)H]glucose was used as tracer for quantifying glycolysis, and the magnitude of the 3H retention was influenced by the presence of other substrates and metabolites. Detritiation was at least 99% complete, however, when [3-(3)H]glucose was used as tracer in this system and the tritium was recovered as 3H2O. Glycolytic flux was six- to sevenfold higher in cells of the proximal than distal small intestine but was not significantly different for young adult (4 mo) vs. aged adult (24 mo) rats. Net ATP production from exogenous substrates was higher when both glucose and glutamine were present simultaneously than when either substrate was present alone, and glucose was calculated to provide 50-60% of the net ATP produced from these two substrates. Most of the energy produced from glucose was produced via the anaerobic metabolic pathways (78% for glucose alone, 95% with glucose and glutamine). Net energy production was calculated to be 10% lower in cells from aged animals than in those from young animals, since CO2 production from these major substrates was lower in cells from aged animals.

Intestinal cell respiration is influenced by animal age, strain, and feeding status.

The objectives of this study were to evaluate the influence of aging and the fasted vs fed state on substrate oxidation by jejunal and colonic cells in vitro, and to determine whether the effects of these factors would be influenced by rat strain. Young (4 mo) and aged (24 mo) male rats of the Fischer 344 (F344) and Fischer x Brown Norway (F x BN) strains were used either following a 48-hr fast or in the ad libitum fed state. On the morning of experimentation, cells were removed from segments of the jejunum and colon and aliquots of these suspensions were incubated in 5 mM concentrations of substrates containing trace quantities of 14C-labeled isotopes. Following 60 min of incubation, 14CO2 was collected and quantified to determine substrate oxidation. The oxidation of glucose, glutamine, and 3-hydroxybutyrate was studied in jejunal and colonic cells, and the oxidation of acetate and butyrate was studied in colonic cells only. Glucose oxidation by jejunal cells was lower when cells were taken from 48-hr fasted animals than from fed animals, but the feeding status of the animal did not significantly influence oxidation of other substrates by jejunal or colonic cells. Substrate oxidation was not different for the F344 vs F x BN strains when jejunal and colonic cells were taken from young animals. Differences due to rat strain became apparent in the aged animals, however, with oxidation of several substrates being higher for the aged F344 than for the aged F x BN animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of dietary fiber on proliferation of intestinal mucosal cells in miniature swine may not be mediated primarily by fermentation.

Cannulated miniature pigs were used as a model for evaluating the effects of fiber-containing diets on proliferation of colonic epithelial cells. Biopsy specimens taken from the mucosa of the cecum and distal colon were incubated in [3H]thymidine and processed using autoradiography. Digesta from the cecum was analyzed for concentrations of short-chain fatty acids (SCFA), pH and volume. Cellular proliferation at both intestinal sites was influenced by the source or quantity of dietary fiber. These dietary variables also influenced SCFA concentrations and pH of cecal digesta and the volume of contents in the fermentation chamber. Cellular proliferation was not significantly correlated, however, with the quantity of water-soluble dietary fiber consumed, with SCFA concentrations or pH of the cecal digesta, or with the volume of the fermentation chamber. We suggest that the influence of dietary fiber on intestinal cell proliferation cannot be predicted from markers of the fermentation capacity of specific diets, because fiber likely influences intestinal proliferation through several interactive mechanisms, some of which include luminal factors.

Absorption of short-chain fatty acids from the rat cecum in vivo.

Absorption of the short-chain fatty acids (SCFA), acetate, propionate and butyrate, was studied in vivo by measuring their disappearance from the washed cecum of anesthetized rats. The SCFA seemed to be absorbed predominantly by simple passive diffusion, because there was linear absorption over a wide concentration range, and no evidence of competition or enhancement of absorption when more than one SCFA was present in the lumen. Absorption of these three SCFA was independent of chain length. Their absorption was clearly limited by the lipid membrane, because permeability through the unstirred water layers was much greater than through the lipid membrane. Absorption was unaffected by altering the pH of the luminal infusate between 5.4 and 7.4. Based on our observation that, during absorption, there were increases in pH, total CO2 and HCO3- but no change in pCO2, we suggest that SCFA are absorbed primarily via diffusion involving anionic exchange with HCO3-.

Nutrient utilization by cells isolated from rat jejunum, cecum and colon.

Cells isolated from the jejunum, cecum and colon of rats were used to study the oxidation of nutrients by quantifying the production of 14CO2 from 5 mmols/L 14C-labeled exogenous substrate. In colonic cells, the decreasing order of oxidation was as follows: butyrate greater than acetate greater than propionate, glucose and glutamine. Acetate and butyrate significantly suppressed oxidation of both glucose and glutamine. In cells taken from the cecum, butyrate was oxidized at a greater rate than all other substrates. Cells taken from the jejunum produced CO2 from exogenous substrates in decreasing order as follows: glutamine greater than glucose much greater than acetate, propionate and butyrate. Butyrate oxidation was significantly reduced in colonic cells by 3-hydroxybutyrate, and it was reduced in cecal cells by glucose. Comparisons among the three gut segments showed no differences in glutamine oxidation. Glucose oxidation was greater in cells taken from the colon than from the cecum or jejunum, which were similar. Butyrate and acetate were oxidized at higher rates in cells taken from the cecum and colon than in cells taken from the jejunum, and propionate was oxidized at a greater rate in cells taken from the colon than from the jejunum. These studies demonstrate that relative rates of substrate oxidation differ along the intestinal tract of rats.

High-fiber diets: influence on characteristics of cecal digesta including short-chain fatty acid concentrations and pH.

The effects of two sources of dietary fiber on the characteristics of cecal contents were assessed directly with miniature swine cannulated to facilitate frequent collections of cecal digesta. The short-chain fatty acid (SCFA) concentrations increased and the pH decreased at the same time that meal constituents entered the cecum; PEG was used as a dietary marker. The bean diet resulted in higher concentrations of acetate and total SCFA in cecal digesta, lower concentrations of butyrate, a larger SCFA pool size, and a more acidic pH than did the bran diet. Thus, we conclude that SCFA concentrations and acidity of the digesta are directly related and that dietary fibers can affect simultaneously several variables that are implicated as factors influencing colonic health.

Locus of control factor structure in a British neurotic sample.

The Reid & Ware Locus of Control Scales, which include a self-control scale, were given to 49 neurotic patients. The three factors reported by Reid & Ware of self-control, social system control and chance were closely replicated.

Pigeons learn the concept of an "A".

Pigeons learned to discriminate between "A"S and "2"s in eighteen different typefaces. They subsequently showed excellent transfer to twenty-two typefaces that they had not previously seen; one pigeon was tested with handwritten letters and responded correctly to them also. Pigeons' responses to "A's and "2's with parts removed suggested that their performance was controlled by several features, none of which alone could be considered necessary or sufficient. A test in which birds were shown other letters of the alphabet supported this conclusion. It appears that the original discrimination was learned as what Ryle calls a "polymorphous concept".