Linoleic Acid: A Nutritional Quandary.

Over the course of the twentieth century, there was a 20-fold increase in consumption of vegetable oils resulting both from their increased availability and from recommendations to consume these oils as an aid to lower blood cholesterol levels. This dietary change markedly increased the consumption of linoleic acid to current levels of approximately 6% of total dietary energy. While considerable research has focused on the effects of dietary linoleic acid on cardiovascular health, questions about optimum dietary levels remain. For example, meta-analyses disagree about the role of dietary linoleic acid in atherosclerosis, and recent publications indicate that linoleic acid's reduction of blood cholesterol levels does not predict its effect on the development of atherosclerosis. Further, there are also detrimental effects of elevated dietary linoleic acid on human health related to its role in inflammation and its activity as a promoter of cancer in animals. Current data do not allow determination of the level of dietary linoleic acid needed for optimum health. Studies of the effects of a wide range of linoleic acid consumption may help determine dietary recommendations that are optimal for human health.

Polyunsaturated fatty acids and recurrent mood disorders: Phenomenology, mechanisms, and clinical application.

A body of evidence has implicated dietary deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of recurrent mood disorders including major depressive disorder (MDD) and bipolar disorder. Cross-national and cross-sectional evidence suggests that greater habitual intake of n-3 PUFA is associated with reduced risk for developing mood symptoms. Meta-analyses provide strong evidence that patients with mood disorders exhibit low blood n-3 PUFA levels which are associated with increased risk for the initial development of mood symptoms in response to inflammation. While the etiology of this n-3 PUFA deficit may be multifactorial, n-3 PUFA supplementation is sufficient to correct this deficit and may also have antidepressant effects. Rodent studies suggest that n-3 PUFA deficiency during perinatal development can recapitulate key neuropathological, neurochemical, and behavioral features associated with mood disorders. Clinical neuroimaging studies suggest that low n-3 PUFA biostatus is associated with abnormalities in cortical structure and function also observed in mood disorders. Collectively, these findings implicate dietary n-3 PUFA insufficiency, particularly during development, in the pathophysiology of mood dysregulation, and support implementation of routine screening for and treatment of n-3 PUFA deficiency in patients with mood disorders.

Docosahexaenoic acid biostatus is associated with event-related functional connectivity in cortical attention networks of typically developing children.

OBJECTIVE: Although extant preclinical evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is important for neurodevelopment, little is known about its role in human cortical structural and functional maturation. In the present cross-sectional study, we investigated the relationship between DHA biostatus and functional connectivity in cortical attention networks of typically developing children. METHODS: Male children (aged 8-10 years, n = 36) were divided into 'low-DHA' (n = 18) and 'high-DHA' (n = 18) biostatus groups by a median split of erythrocyte DHA levels. Event-related functional connectivity during the performance of a sustained attention task (identical pairs continuous performance task (CPT-IP)) was conducted using functional magnetic resonance imaging. A voxelwise approach used the anterior cingulate cortex (ACC) as the seed-region. RESULTS: Erythrocyte DHA composition in the low-DHA group (2.6 ± 0.9%) was significantly lower than the high-DHA group (4.1 ± 1.1%, P ≤ 0.0001). Fish intake frequency was greater in the high-DHA group (P = 0.003) and was positively correlated with DHA levels among all subjects. The low-DHA group exhibited reduced functional connectivity between the ACC and the ventrolateral prefrontal cortex, insula, precuneus, superior parietal lobule, middle occipital gyrus, inferior temporal gyrus, and lingual gyrus compared with the high-DHA group (P < 0.05; corrected). The low-DHA group did not exhibit greater ACC functional connectivity with any region compared with the high-DHA group. On the CPT-IP task, the low-DHA group had slower reaction time (P = 0.03) which was inversely correlated with erythrocyte DHA among all subjects. DISCUSSION: These data suggest that low-DHA biostatus is associated with reduced event-related functional connectivity in cortical attention networks of typically developing children.

Intervention to reduce PCBs: learnings from a controlled study of Anniston residents.

Nonabsorbable dietary lipid reduces the absorption of dietary PCBs and increases the excretion of previously absorbed stored PCBs. Absorption of all PCB congeners will presumably be interrupted by nonabsorbable lipid; however excretion will be enhanced only for PCBs that have not been metabolized and also for their lipophilic metabolites. Our study with the nonabsorbable lipid, olestra, in a controlled trial in Anniston residents with elevated PCB levels demonstrated that it is possible to enhance removal of PCBs from the body in the clinically meaningful time frame of 1 year. The rate of disappearance of PCBs in participants who ate 15 g/day of olestra was significantly faster than the rate determined during the 5 years prior to intervention. The rate of disappearance was not changed from the pretrial rate in participants who ingested vegetable oil. Consideration of the role of body weight and fat is an important factor in the design of intervention trials of this kind, and the results of this trial suggest that the level of body fat in individuals will influence the rate of removal from the body. Previously reported data from animals and from a case report indicate that weight loss combined with nonabsorbable dietary lipid will maximize removal of PCBs and presumably other stored organochlorine compounds. The design of future intervention trials should include a focus on body fat levels and changes. Future trials should also include the testing of dietary compounds other than olestra that have affinity for PCBs, such as plant-derived polyphenols.

Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial.

Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 non-coplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (-0.0829 ± 0.0357 and -0.00864 ± 0.0116 year(-1), respectively; P=.04), but not during VO consumption (-0.0413 ± 0.0408 and -0.0283 ± 0.0096 year(-1), respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes.

An assessment of the intestinal lumen as a site for intervention in reducing body burdens of organochlorine compounds.

Many individuals maintain a persistent body burden of organochlorine compounds (OCs) as well as other lipophilic compounds, largely as a result of airborne and dietary exposures. Ingested OCs are typically absorbed from the small intestine along with dietary lipids. Once in the body, stored OCs can mobilize from adipose tissue storage sites and, along with circulating OCs, are delivered into the small intestine via hepatic processing and biliary transport. Retained OCs are also transported into both the large and small intestinal lumen via non-biliary mechanisms involving both secretion and desquamation from enterocytes. OCs and some other toxicants can be reabsorbed from the intestine, however, they take part in enterohepatic circulation(EHC). While dietary fat facilitates the absorption of OCs from the small intestine, it has little effect on OCs within the large intestine. Non-absorbable dietary fats and fat absorption inhibitors, however, can reduce the re-absorption of OCs and other lipophiles involved in EHC and may enhance the secretion of these compounds into the large intestine--thereby hastening their elimination. Clinical studies are currently underway to determine the efficacy of using non-absorbable fats and inhibitors of fat absorption in facilitating the elimination of persistent body burdens of OCs and other lipophilic human contaminants.

The transport of DDT from chylomicrons to adipocytes does not mimic triacylglycerol transport.

Despite being banned in the U.S., organochlorine toxins such as DDT are frequently detected in human adipose tissue. The main route of exposure is through the consumption of contaminated foods and subsequent intestinal packaging of DDT into chylomicrons. These chylomicrons, which also contain dietary triacylglycerol (TG), are delivered directly to peripheral tissues without first being metabolized by the liver. The physiological process by which these compounds are delivered from chylomicrons to adipose is not well understood, but is clinically relevant since it bypasses first-pass metabolism. Based on its highly lipophilic nature, it has been assumed that DDT is transferred to peripheral tissues similar to TG; however, this has not been measured. Here, we use the lymph fistula rat to isolate chylomicrons containing both DDT and TG. These chylomicrons are the in vivo DDT delivery vehicle. Using 3T3-L1 adipocytes, we investigated the rate at which DDT transfers from chylomicrons to adipocytes, and mediators of this process. This novel approach closely approximates the in vivo DDT exposure route. We show that: 1) DDT repartitions from chylomicrons to adipocytes, 2) this transport does not require hydrolysis of TG within the chylomicron, and is stimulated by the inhibition of LPL, 3) albumin does not inhibit DDT uptake, 4) DDT dissolved in DMSO does not appropriately mimic in vivo DDT transport; and most importantly, 5) DDT uptake from chylomicrons does not mimic the uptake of TG from the same particles. Understanding these factors is important for designing interventions for human populations exposed to DDT.

Review of the effects of dilution of dietary energy with olestra on energy intake.

The non-absorbable substitute for dietary triacylglycerol, olestra, has been marketed in the United States for fifteen years. Olestra is comprised of sucrose with six to eight of its hydroxyl groups forming ester links with long-chain fatty acids. Because olestra is not hydrolyzed by fat-splitting enzymes in the small intestine, it is not absorbed from the small intestine into blood and tissues, and therefore provides no energy that can be utilized by the body. The hedonic properties of olestra with a specific fatty acid composition are similar to those of a triacylglycerol with the same fatty acid composition. Its use by consumers has been restricted by federal regulation to the commercial preparation of savory snack food items, principally as a frying medium for potato chips. An important question about the substitution of olestra for absorbable fat in the diet is whether the consumer will sense that a smaller amount of energy has been ingested. If it is sensed, thereby providing no satiation, then consuming additional energy in later meals will compensate for the removal of absorbable energy from the diet. If it is not sensed at all, then there is no compensation, and the person reduces caloric intake. This review first summarizes studies with olestra that have focused on its effect on the physiology of appetite. In general these studies have demonstrated that olestra does not influence signals of satiation including cholecystokinin and stomach emptying. The review then discusses studies of food consumption in experimental animals in which olestra was substituted for fat in the diet. Rodents have been repeatedly observed to compensate completely for the substitution of olestra for normal fat by eating more total diet. Most studies of the effect of olestra on human satiation have found incomplete or no compensation through additional energy consumption when olestra was substituted for dietary fat. In two clinical studies, however, complete compensation was observed, suggesting that experimental conditions and individual variability influence the ability to sense the substitution of olestra for absorbable fat. There is no evidence that dietary olestra causes consumption of more energy than would have been consumed without olestra in the diet. The data from animals and humans strongly suggest that the rodent is not a satisfactory model for the human in the determination of the extent of compensation by substitution of olestra for dietary fat.

Apolipoprotein E reduces food intake via PI3K/Akt signaling pathway in the hypothalamus.

Apolipoprotein E (apoE) is a satiation factor. While central apoE administration reduces food intake, the specific intracellular signaling mechanisms activated by apoE remain largely unknown. Using primary cultured hypothalamic neurons, we demonstrated that apoE treatment (50 nM) elicited rapid activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling cascade. Specifically, apoE induced the phosphorylation of Akt, peaking at 30 min, and the increased phosphorylation of Akt was significantly attenuated after pretreatment with LY294002 (50 µM), an inhibitor of the PI3K signaling pathway. To determine whether the activation of PI3K by apoE is required for the ability of apoE to reduce food intake, LY294002 (1 nmol) was infused into the 3rd-cerebral ventricle before injection of an anorectic dose of apoE. Consistent with our previous report, apoE (4 µg) exerted significant reduction of food intake in the 4-h fasted rats, compared with saline. Pretreatment with LY294002 significantly attenuated the potency of exogenous apoE to induce satiation, while the same dose of PI3K inhibitor by itself caused only a slight non-significant decrease of food intake. These results indicate that the activation of the PI3K/Akt pathway is necessary for the acute effects of apoE on food intake.

Bypassing the duodenum does not improve insulin resistance associated with diet-induced obesity in rodents.

Roux-en-y gastric bypass (RYGB) surgery rapidly improves glucose tolerance and reverses insulin resistance in obese patients. It has been hypothesized that this effect is mediated by the diversion of nutrients from the proximal small intestine. We utilized duodenal-jejunal bypass (DJB) as a modification of gastric bypass to determine the effect of nutrient diversion from the foregut without gastric restriction on insulin resistance in obese rats. The effects of DJB or Sham surgery on glucose homeostasis were determined in both high-fat-fed Long-Evans and Wistar rats. Body weight and food intake were measured weekly postoperatively, and body composition was monitored before and after surgery. Glucose tolerance was tested before and as early as 1 month postoperation; additionally, in Wistar rats, insulin sensitivity was determined by a hyperinsulinemic-euglycemic clamp (HIEC). DJB did not affect body weight, body composition, glucose tolerance, or insulin concentrations over the period of the study. The average glucose infusion rate (GIR) during the HIEC was 6.2 ± 1.16 mg/kg/min for Sham rats compared to 7.2 ± 1.71 mg/kg/min for DJB rats (P = 0.62), and neither endogenous glucose production (EGP; P = 0.81) nor glucose utilization (glucose disappearance (R(d)), P = 0.59) differed between DJB and Sham rats. DJB does not affect insulin resistance induced by a high-fat diet in Long-Evans and Wistar rats. These data suggest that duodenal bypass alone is an insufficient mechanism to alter insulin sensitivity independent of weight loss in obese, nondiabetic rodents.

Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities.

Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome. Changes in intestinal and hepatic physiology after ileal interposition (transposition) surgery (IIS) are not well understood. Our aim was to elucidate the adaptation of the interposed ileum, which we hypothesized, would lead to early bile acid reabsorption in the interposed ileum, thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments. Rats with diet-induced obesity were randomized to IIS, with 10 cm of ileum repositioned distal to the duodenum, or sham surgery. A subgroup of sham rats was pair-fed to IIS rats. Physiological parameters were measured until 6 wk postsurgery. IIS rats ate less and lost more weight for the first 2 wk postsurgery. At study completion, body weights were not different, but IIS rats had reversed components of the metabolic syndrome. The interposed ileal segment adapted to a more jejunum-like villi length, mucosal surface area, and GATA4/ILBP mRNA. The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi. IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum, suggesting an early and efficient reabsorption of primary bile acids. IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss. There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR, SHP, or NTCP expression. IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling. There is early reabsorption of primary bile acids despite selective "jejunization" of the interposed ileal segment. Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery.

Perinatal exposure to bisphenol-a and the development of metabolic syndrome in CD-1 mice.

Bisphenol-A (BPA) is an endocrine-disrupting chemical used in the production of plastic food and beverage containers, leading to ubiquitous low-dose human exposure. It has been suggested that exposure to even low doses of BPA during development may be associated with increased susceptibility to obesity and diabetes later in life. Despite growing public concern, the existing empirical data are equivocal, prompting The Endocrine Society, the National Institute of Environmental Health Sciences, and others to call for further research. In this study, we tested the hypothesis that perinatal exposure to an ecologically relevant dose of BPA (1 part per billion via the diet) results in increased susceptibility to high-fat diet-induced obesity and glucose intolerance in adult CD-1 mice. The data did not support this hypothesis. In agreement with previous reports, we find that weanling mice exposed to BPA during gestation and lactation are heavier compared with control mice. We also find that BPA mice are longer than controls at 4 wk of age, but these differences are no longer apparent when the mice reach adulthood, even when tested on a high-fat diet. We conclude that this larger size-for-age represents a faster rate of growth early in development rather than an obese, diabetic phenotype in adulthood.

Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity.

Decrease in fat catabolic rate on consuming a high-fat diet contributes to diet-induced obesity. This study used group 1B phospholipase A(2) (Pla2g1b)-deficient mice, which are resistant to hyperglycemia, to test the hypothesis that Pla2g1b and its lipolytic product lysophospholipid suppress hepatic fat utilization and energy metabolism in promoting diet-induced obesity. The metabolic consequences of hypercaloric diet, including body weight gain, energy expenditure, and fatty acid oxidation, were compared between Pla2g1b(+/+) and Pla2g1b(-/-) mice. The Pla2g1b(-/-) mice displayed normal energy balance when fed chow, but were resistant to obesity when challenged with a hypercaloric diet. Obesity resistance in Pla2g1b(-/-) mice is due to their ability to maintain elevated energy expenditure and core body temperature when subjected to hypercaloric diet, which was not observed in Pla2g1b(+/+) mice. The Pla2g1b(-/-) mice also displayed increased postprandial hepatic fat utilization due to increased expression of peroxisome proliferator-activated receptor (PPAR)-alpha, PPAR-delta, PPAR-gamma, cd36/Fat, and Ucp2, which coincided with reduced postprandial plasma lysophospholipid levels. Lysophospholipids produced by Pla2g1b hydrolysis suppress hepatic fat utilization and down-regulate energy expenditure, thereby preventing metabolically beneficial adaptation to a high-fat diet exposure in promoting diet-induced obesity and type 2 diabetes.

Cholecystokinin knockout mice are resistant to high-fat diet-induced obesity.

BACKGROUND & AIMS: Cholecystokinin (CCK) is a satiation peptide released during meals in response to lipid intake; it regulates pancreatic digestive enzymes that are required for absorption of nutrients. We proposed that mice with a disruption in the CCK gene (CCK knockout [CCK-KO] mice) that were fed a diet of 20% butter fat would have altered fat metabolism. METHODS: We used quantitative magnetic resonance imaging to determine body composition and monitored food intake of CCK-KO mice using an automated measurement system. Intestinal fat absorption and energy expenditure were determined using a noninvasive assessment of intestinal fat absorption and an open circuit calorimeter, respectively. RESULTS: After consuming a high-fat diet for 10 weeks, CCK-KO mice had reduced body weight gain and body fat mass and enlarged adipocytes, despite the same level of food intake as wild-type mice. CCK-KO mice also had defects in fat absorption, especially of long-chain saturated fatty acids, but pancreatic triglyceride lipase did not appear to have a role in the fat malabsorption. Energy expenditure was higher in CCK-KO than wild-type mice, and CCK-KO mice had greater oxidation of carbohydrates while on the high-fat diet. Plasma leptin levels in the CCK-KO mice fed the high-fat diet were markedly lower than in wild-type mice, although levels of insulin, gastric-inhibitory polypeptide, and glucagon-like peptide-1 were normal. CONCLUSIONS: CCK is involved in regulating the metabolic rate and is important for lipid absorption and control of body weight in mice placed on a high-fat diet.

Fat malabsorption in cystic fibrosis: comparison of quantitative fat assay and a novel assay using fecal lauric/behenic acid.

OBJECTIVES: The gold standard for the diagnosis of fat malabsorption, the 72-hour fat balance study, requires a 3-day collection to generate a coefficient of fat absorption (CFA). We hypothesized that a new test using behenic acid (behenate test) as a nonabsorbable lipid marker may provide a facile means to assess fat absorption. The study proposed to answer 2 questions: first, whether the behenate test correlated with the gold standard and, second, whether the CFA improved when taking pancreatic enzymes during meals instead of taking them before meals. PATIENTS AND METHODS: The study compared the behenate test with the gold standard in 15 patients with cystic fibrosis during 3 arms that require 3- to 4-day hospitalization: first, taking pancreatic enzymes before meals; second, taking it during meals; and third, without taking it. RESULTS: The mean CFA was 78.3% when pancreatic enzymes were taken during meals and 80.4% when these enzymes were taken before meals. Correlation between the CFA and the behenate test for collections during all 3 arms was r = 0.219 (P = 0.001). CONCLUSIONS: Timing of ingestion of pancreatic enzymes does not significantly alter the CFA. Although the CFA correlates with the behenate test, the correlation is not robust enough to justify replacement of the gold standard by this test. It is unclear whether the poor correlation between tests relates to intermeal variability in fat excretion or other factors; however, the behenate test may be suitable as a screening test for the detection of fat malabsorption.

Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies.

The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.

GOAT links dietary lipids with the endocrine control of energy balance.

Central nervous system nutrient sensing and afferent endocrine signaling have been established as parallel systems communicating metabolic status and energy availability in vertebrates. The only afferent endocrine signal known to require modification with a fatty acid side chain is the orexigenic hormone ghrelin. We find that the ghrelin O-acyl transferase (GOAT), which is essential for ghrelin acylation, is regulated by nutrient availability, depends on specific dietary lipids as acylation substrates and links ingested lipids to energy expenditure and body fat mass. These data implicate the ghrelin-GOAT system as a signaling pathway that alerts the central nervous system to the presence of dietary calories, rather than to their absence as is commonly accepted.

One-year comparison of a high-monounsaturated fat diet with a high-carbohydrate diet in type 2 diabetes.

OBJECTIVE: The purpose of this study was to compare the effects of high-monounsaturated fatty acid (MUFA) and high-carbohydrate (CHO) diets on body weight and glycemic control in men and women with type 2 diabetes. RESEARCH DESIGN AND METHODS: Overweight/obese participants with type 2 diabetes (n = 124, age = 56.5 +/- 0.8 years, BMI = 35.9 +/- 0.3 kg/m2, and A1C = 7.3 +/- 0.1%) were randomly assigned to 1 year of a high-MUFA or high-CHO diet. Anthropometric and metabolic parameters were assessed at baseline and after 4, 8, and 12 months of dieting. RESULTS: Baseline characteristics were similar between the treatment groups. The overall retention rate for 1 year was 77% (69% for the high-MUFA group and 84% for the high-CHO group; P = 0.06). Based on food records, both groups had similar energy intake but a significant difference in MUFA intake. Both groups had similar weight loss over 1 year (-4.0 +/- 0.8 vs. -3.8 +/- 0.6 kg) and comparable improvement in body fat, waist circumference, diastolic blood pressure, HDL cholesterol, A1C, and fasting glucose and insulin. There were no differences in these parameters between the groups. A follow-up assessment of a subset of participants (n = 36) was conducted 18 months after completion of the 52-week diet. These participants maintained their weight loss and A1C during the follow-up period. CONCLUSIONS: In individuals with type 2 diabetes, high-MUFA diets are an alternative to conventional lower-fat, high-CHO diets with comparable beneficial effects on body weight, body composition, cardiovascular risk factors, and glycemic control.

Lymphatic and portal vein absorption of organochlorine compounds in rats.

The route of absorption of ingested compounds is a determinant of their distribution and metabolism. Portal vein absorption results in direct transport to the liver, where metabolism may take place before extrahepatic delivery. Lymphatic absorption can result in delivery of parent compound to nonhepatic tissues. Understanding the fate of an ingested compound requires determination of the importance of each of these routes. Portal vein absorption can be estimated from the difference in concentrations of an ingested compound between the portal vein and peripheral vessel blood. To make these estimations, one must make assumptions on the basis of estimates of flow rate and dilution. We report here methodology that allows a direct measurement of portal vein absorption that is independent of these assumptions. Mesenteric lymph was diverted from rats by cannulation. Portal blood was sampled after duodenal infusion of a bolus of compound of interest along with a portal absorption marker, 3-O-methylglucose. Since lymph was diverted, the appearance in portal blood was solely the result of portal absorption. Absorption was quantified by the areas under the curve for the compound and marker. Portal absorption was a function of the octanol/water partition coefficients for four organochlorine compounds: hexachlorobenzene, pentachlorophenol, DDT, and its metabolite 1,1,1-trichloro-2,2-bischlorophenylethylene.

GATA4 is essential for jejunal function in mice.

BACKGROUND & AIMS: Although the zinc-finger transcription factor GATA4 has been implicated in regulating jejunal gene expression, the contribution of GATA4 in controlling jejunal physiology has not been addressed. METHODS: We generated mice in which the Gata4 gene was specifically deleted in the small intestinal epithelium. Measurements of plasma cholesterol and phospholipids, intestinal absorption of dietary fat and cholesterol, and gene expression were performed on these animals. RESULTS: Mice lacking GATA4 in the intestine displayed a dramatic block in their ability to absorb cholesterol and dietary fat. Comparison of the global gene expression profiles of control jejunum, control ileum, and GATA4 null jejunum by gene array analysis revealed that GATA4 null jejunum lost expression of 53% of the jejunal-specific gene set and gained expression of 47% of the set of genes unique to the ileum. These alterations in gene expression included a decrease in messenger RNAs (mRNAs) encoding lipid and cholesterol transporters as well as an increase in mRNAs encoding proteins involved in bile acid absorption. CONCLUSIONS: Our data demonstrate that GATA4 is essential for jejunal function including fat and cholesterol absorption and confirm that GATA4 plays a pivotal role in determining jejunal vs ileal identity.