Mechanisms Preserving Insulin Action during High Dietary Fat Intake

1. Download high-res image (196KB)
2. Download full-size image

     

Composition of Dietary Fat Affects Blood Pressure and Insulin Responses to Dietary Obesity in the Dog

Cardiovascular and metabolic parameters were evaluated in 15 female spayed dogs before and after they became obese on either a saturated fat (LD, lard, n=8) or unsaturated fat (CO, corn oil, n=7) diet. Body weight and body fat increased significantly in both groups, although no differences occurred between diet groups. Dogs receiving the LD diet exhibited a greater increase in mean arterial pressure than those receiving the CO diet (p<0. 01; 15. 9 ± 2. 1 vs. 9. 8 ± 3. 3 mm Hg increase). The CO diet stimulated a greater increase in heart rate than the LD diet (p<0. 05; 32. 8 ± 7. 8 vs. 14. 1 ± 5. 8 bpm increase). Ganglionic blockade with chlorisondamine caused an increase in HR in both lean groups and in the obese CO group, but not the obese LD group, consistent with a decrease in parasympathetic tone to the heart in the dogs overfed saturated fat. Obesity enhanced the heart rate response to β-badrenergic stimulation by isoproterenol in the LD, but not CO group. The LD diet increased circulating insulin and decreased insulin sensitivity, whereas the CO diet had no effect on either parameter. These findings suggest that the composition of dietary fat can modulate the autonomic and metabolic adaptations induced by dietary obesity.     

Trafficking of Dietary Fat in Lean Rats

BESSESEN, DANIEL H, CONNIE L RUPP AND ROBERT H ECKEL. Trafficking of dietary fat in lean rats. Obes Res. 1995;3:191–203. Despite increasing interest in the role that fuel partitioning plays in determining body composition, the relative importance of oxidative versus storage pathways in the clearance of dietary fat remains unclear. A widely held view is that the primary destination of chylomicron triglyceride fatty acids (TGFA) is adipose tissue, and the primary source of lipid fuel for skeletal muscle is non-esterified fatty acids (NEFA). An alternate view is that muscle, not adipose tissue, is the primary site of TGFA clearance. This view is supported by estimates of the total lipoprotein lipase content of muscle and adipose tissue. To directly study the partitioning of dietary fat between oxidation and storage, ¹⁴C-labeled oleic acid was fed to Sprague Dawley rats and its metabolic fate followed over 30 days. Two hours after ingestion, more than 3.5 times as much label was found in skeletal muscle tissue (2.42 ± 0.45 nmols) and CO₂ (0.25 ± 0.01 nmols) than was found in adipose tissue (0.71 ± 0.14 nmols). Intramuscular triglyceride was the lipid class most extensively labeled. After skeletal muscle, liver was the next most important site of TGFA clearance. Surprisingly a substantial quantity of label remained associated with the GI tract even 24 hours after ingestion. Between 2 and 10 days following ingestion there was a net decline in the C content of muscle, liver and GI tract, associated with a net rise in the ¹⁴C content of adipose tissue. These findings demonstrate: 1) the importance of skeletal muscle and liver in whole organism TGFA clearance, 2) the importance of intramuscular partitioning of lipid fuels between direct oxidation and storage as TG, 3) the potentially important role of the GI tract in the delivery of dietary fat to the circulation 10–24 hours following ingestion, and 4) the stability of adipose tissue as a storage site. The complex nature of the tissue-specific clearance of TGFA over time is perhaps better described by the term ‘trafficking’ than by the more commonly used term “partitioning.” Future studies of TGFA clearance combined with sampling of relevant tissues over time will provide insight into the specific roles that abnormalities in liver, muscle and adipose tissue TGFA metabolism play in the development of hypertriglyceridemic disorders and states of increased or reduced body weight.     

Dietary Fat Is Shunted Away from Oxidation,Toward Storage in Obese Zucker Rats

BESSESEN, DANIEL H, CONNIE L RUPP AND ROBERT H ECKEL. Dietary fat is shunted away from oxidation, toward storage in obese zucker rats. Obes Res. 1995;3:179–189. Previous measurements of lipoprotein lipase (LPL) activity in adipose tissue (ATLPL) of lean and obese Zucker rats have consistently documented increased activity in obese rats relative to lean. Since LPL is considered to be rate limiting for the delivery of triglyceride fatty acids (TGFA) to muscle and adipose tissue, these data have been used to suggest that the metabolic partitioning of TGFA favors storage over oxidation in obese rats. To document the partitioning of TGFA directly, the fate of ¹⁴C labeled oleic acid (42nmols) was fed to lean, obese, and obese Zucker rats fed a hypocaloric diet designed to chronically reduce weight 25% below that of obese controls (reduced-obese). The amount of ¹⁴C recovered in CO₂ over 6 hours following ingestion was significantly less in obese rats compared to lean (0.45 ± 0.06 vs. 0.88 ± 0.09nmols, p=.0004) and less still in the reduced obese group (0.34 ± 0.06nmols p=.00003). Six hours after ingestion, the quantity of label found in adipose tissue was significantly greater in the obese rats compared to lean (14.51 ± 1.92 vs. 1.38 ± 0.29nmols p<.00001), but was intermediate in the reduced-obese group (9.23 ± 0.98nmols p=.0003). At 2.2 hours there was significantly more label in skeletal muscle of lean rats compared to either obese or reduced-obese (2.33 ± 0.24; 1.35 ± 0.04nmols p=.01; 1.41 ± 0.27nm p=.02). However, at 6 hours these differences between groups were no longer present. These findings Indicate that dietary fat is shunted away from oxidation toward storage in obese Zucker rats. Additionally it appears that there may be a relative block in the oxidation of TGFA that is taken up by skeletal muscle in obese rats. Finally the relative normalization of this partitioning defect in reduced-obese rats is at variance with what was suggested by previous measurements of tissue specific levels of LPL, and suggests an enhanced recirculation of fatty acids from adipose tissue to muscle in reduced-obese rats. This could occur through increased delivery of non-esterified fatty acids (NEFA) to muscle as a result of an increase in net lipolysis.     

Dietary Fat Intake and Insulin Resistance in Black and White Children

Objective: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. Research Methods and Procedures: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24‐hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above‐AMDR/within‐AMDR guidelines), and differences were analyzed by 2 × 2 analysis of covariance, adjusting for covariates. Results: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above‐AMDR compared with within‐AMDR blacks) and was not seen in whites. Discussion: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation.     

Elevated Insulin Sensitivity in Low‐protein Offspring Rats Is Prevented by a High‐fat Diet and Is Associated With Visceral Fat

This study tests the hypothesis that a high‐fat postnatal diet increases fat mass and reduces improved insulin sensitivity (IS) found in the low‐protein model of maternal undernutrition. Offspring from Wistar dams fed either a 20% (control (CON)) or 8% (low protein (LP)) protein diet during gestation and lactation were randomly assigned to a control (con) or cafeteria (caf) diet at weaning (21 days) until 3 months of age at which point IS was measured (hyperinsulinemic–euglycemic clamp). Fat mass, growth, energy intake (EI) and expenditure (EE), fuel utilization, insulin secretion, and leptin and adiponectin levels were measured to identify a possible role in any changes in IS. IS was increased in LP‐con in comparison to CON‐con animals. Cafeteria feeding prevented this increase in LP animals but had no effect in CON animals (insulin‐stimulated glucose infusion rates (GIRs; mg/min/kg); CON‐con: 13.9 ± 1.0, CON caf: 12.1 ± 2.1, LP‐con: 25.4 ± 2.0, LP‐caf: 13.7 ± 3.7, P < 0.05). CON‐caf animals had similar percent epididymal white adipose tissue (%EWAT; CON‐con: 1.71 ± 0.09 vs. CON‐caf: 1.66 ± 0.08) and adiponectin (µg/ml: CON‐con: 4.61 ± 0.34 vs. CON‐caf: 3.67 ± 0.18) except hyperinsulinemia and relative hyperleptinemia in comparison to CON‐con. Differently, LP‐caf animals had increased %EWAT (LP‐con: 1.11 ± 0.06 vs. LP‐caf: 1.44 ± 0.08, P < 0.05) and adiponectin (µg/ml: LP‐con: 5.38 ± 0.39 vs. LP‐caf: 3.75 ± 0.35, P < 0.05) but did not show cafeteria‐induced hyperinsulinemia or relative hyperleptinemia. An increased propensity to store visceral fat in LP animals may prevent the elevated IS in LP offspring.     

Role of Some Hormones in Protein Sparing Action of Dietary Fat

Feeding rats with a fat meal caused marked reduction in the level of plasma urea and urinary output of urea and total nitrogen. Experiments were carried out to examine the possible intervention of some hormones in these phenomena. Protein sparing action of fat was exerted even in the alloxan-diabetic, adrenalectomized, hypophysectomized and thyroidectomized rats. Feeding rats with a fat meal caused no appreciable change in the level of cyclic AMP in liver and gastrocnemius muscle. The overall results obtained here are through! to suggest that the action of fat may be exerted independently of any hormones examined; insulin, glucocorticoids, cyclic AMP and other hormones excreted from adrenal, hypophysis and thyroid gland.     

Influence of Dietary Carbohydrate,Fat, and Protein on Lipogenesis in Rats

The incorporation of ¹⁴C of acetate-1-¹⁴C into the lipids of the liver and carcass, and the changes in the concentrations of nucleotides and citric acid in the liver were studied in the rats fed individual nutrients; starch, casein or corn oil. And the metabolism of citric acid-1,5-¹⁴C was also investigated after the feeding of nutrients. Lipogenesis in the liver and carcass was more markedly stimulated with starch than with casein or corn oil. In the liver of rats fed starch, the concentration of ATP doubled and that of citric acid was one-half of those with casein or corn oil, respectively. And the conversion of citric acid to carbon dioxide and lipids was stimulated with starch.     

Reversal of Osteoporotic Changes of Mineral Composition in Femurs of Diabetic Rats by Insulin

Insulin plays an important role in bone prevention of diabetic osteoporosis, but little is known about the relation between the bone mineral density (BMD) increase and the change of mineral element content after treated with insulin. To address this problem, male Wistar rats were randomly divided into three groups: normal group (n = 6), streptozotocin-induced diabetic group (n = 5), and streptozotocin-induced diabetic group with insulin treatment (n = 5). The femoral BMD was measured by dual energy X-ray absorptiometry, and the element content was determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). The results showed that the femoral BMD in diabetic group was significantly lower than that in normal group (P < 0.01) but restored by insulin treatment (P < 0.01 vs diabetic group). ICP-AES analysis revealed that the element content of calcium (Ca), phosphorous (P), magnesium (Mg), strontium (Sr), and potassium (K) in diabetic group were remarkably lower than those in normal group (P < 0.01) but only Ca, P, and Mg content were significantly increased compared with diabetic group (P < 0.05) after insulin treatment. However, no significant differences were observed in element zinc (Zn) content among three groups. Our findings suggested that the loss of Ca, P, Mg, Sr, and K content accounted for the lower BMD in streptozotocin-induced diabetes rats, insulin treatment could restore BMD by increasing the content of Ca, P, and Mg.     

Dietary Energy Density Affects Fat Mass in Early Adolescence and Is Not Modified by FTO Variants

Background

Dietary energy density (DED) does not have a simple linear relationship to fat mass in children, which suggests that some children are more susceptible than others to the effects of DED. Children with the FTO (rs9939609) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised. We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants.

Methods and Findings

We carried out a prospective analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Diet was assessed at age 10 y using 3-day diet diaries. DED (kJ/g) was calculated excluding drinks. Children were genotyped for the FTO (rs9939609) variant. Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner. There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y (β = 0.005, p = 0.51), suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35±0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16±0.06 kg more fat mass at age 13 y, after controlling for misreporting of energy intake, gender, puberty, overweight status at 10 y, maternal education, TV watching, and physical activity.

Conclusions

This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity, encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain.     

The Composition of Fluorescent Pseudomonad Populations Associated with Roots Is Influenced by Plant and Soil Type

Populations of fluorescent pseudomonads isolated from an uncultivated soil and from the roots of two plant species were previously shown to differ (P. Lemanceau, T. Corberand, L. Gardan, X. Latour, G. Laguerre, J.-M. Boeufgras, and C. Alabouvette, Appl. Environ. Microbiol. 61:1004-1012, 1995). The diversities of fluorescent pseudomonads, from two uncultivated soils and from the roots of two plant species cultivated in these two soils, were compared. The phenotypic diversity of the bacterial isolates was characterized on the basis of biochemical and physiological tests and on the basis of their ability to utilize 147 different organic compounds. The genotypic diversity of the isolates was characterized on the basis of the types of 16S genes coding for rRNA (rDNA), their repetitive extragenic palindromic patterns by PCR, and plasmid profiles. Taxonomic identification of the isolates was achieved with both biochemical and physiological tests and by comparing their 16S rDNA types to those of reference and type strains of fluorescent Pseudomonas spp. Numerical analysis of phenotypic characteristics allowed the clustering of isolates that showed high levels of similarity. This analysis indicated that both soil type and host plant had an effect on the diversity of fluorescent pseudomonads. However, of the two factors studied, the soil was clearly the dominating one. Indeed, the populations associated with the roots of each plant species varied from one soil to the other. This variation could possibly be ascribed to the differences recorded between the phenotypically diverse populations of fluorescent pseudomonads from the two uncultivated soils. The plant selection was, at least partly, plant specific. It was not related to bacterial species and biovars or to the presence of plasmid DNA. The phenotypic clustering of isolates was well correlated with genotypic characterization by repetitive extragenic palindrome-PCR fingerprinting.     

Repair of a Mismatch Is Influenced by the Base Composition of the Surrounding Nucleotide Sequence

Heteroduplexes with single base pair mismatches of known sequence were prepared by annealing separated strands of bacteriophage lambda DNA and used to transfect Escherichia coli. A series of transition (G:T and A:C) and transversion (G:A and C:T) mismatches located throughout most of the bacteriophage lambda cI gene has been examined. The results suggest that the transition mismatches are generally better repaired than the transversion mismatches and that, at least for the transversion mismatches studied, repair efficiency increases with increasing G:C content in the neighboring nucleotide sequence. This specificity of the E. coli mismatch repair system can account, in part, for the similar frequencies of base substitution mutations throughout the E. coli genome.     

High Dietary Calcium Reduces Body Fat Content,Digestibility of Fat,and Serum Vitamin D in Rats

Objective: This study investigated which aspect of energy balance was responsible for the decrease in body fat content of rats fed a high‐calcium, high—dairy protein diet. Research Methods and Procedures: Male Wistar rats were fed a control diet (25% kcal fat, 14% kcal protein from casein, 0.4% by weight calcium) or high‐calcium diet (25% kcal fat, 7% kcal protein from nonfat dry milk, 7% kcal protein from casein, 2.4% calcium) for 85 days. Body weights, digestible energy intakes, energy expenditures, rectal temperatures, body composition, and serum glucose, insulin, free fatty acids, triglycerides, and 1, 25‐dihydroxyvitamin D were measured. Results: Rats fed high‐calcium diet gained significantly less weight than controls and had 29% less carcass fat. Gross energy intake was not significantly different between groups, but digestible energy was 90% of gross energy in the high‐calcium diet compared with 94% in the control diet because of increased fecal excretion of dietary lipid. The difference in digestible energy intake accounted for differences in carcass energy. Body temperatures and energy expenditures of the rats were not different. The high‐calcium diet reduced serum triglycerides by 23% and serum 1, 25‐dihydroxyvitamin D by 86%. Discussion: These results confirm that a high‐calcium diet decreases body weight and fat content due to a lower digestible energy intake caused by increased fecal lipid and a nonsignificant reduction in gross energy intake.     

Serum Glycated Albumin Is Inversely Influenced by Fat Mass and Visceral Adipose Tissue in Chinese with Normal Glucose Tolerance

Background

Recent studies have revealed that body mass index (BMI) inversely influenced serum glycated albumin (GA), which may cause an underestimation of GA-monitored short-term hyperglycemic control.

Objective

This study was to investigate the association between anthropometric variables (BMI and waist circumference (W)) and accurate adiposity variables (percentage of body fat (%fat), fat mass, free fat mass (FFM), subcutaneous fat area (SFA), and visceral fat area (VFA)) with serum GA.

Design

A total of 2563 subjects (1037 men, 593 premenopausal women, and 933 postmenopausal women) with normal glucose tolerance underwent bioelectrical impedance body fat content measurement and magnetic resonance imaging. Serum GA and absolute value of GA (aGA) were measured by enzymatic assay.

Results

Compared to the BMI <25.0 kg/m² group, the BMI ≥25.0 kg/m² group had significantly higher fasting plasma glucose, glycated hemoglobin A1c, and body fat parameters including W, %fat, fat mass, FFM, SFA, and VFA, but significantly lower aGA, and GA in all the three sex- and menopause-stratified groups (all P<0.05). GA decreased with the increment of fat mass for all three groups (all P for trend <0.001). In the same BMI category, men and postmenopausal women with elevated %fat (men, ≥25%; women, ≥35%) still had significantly lower GA than those with normal %fat (men, <25%; women, <35%) (all P<0.05). Multiple stepwise regression showed that %fat, fat mass, and VFA were independently associated with GA.

Conclusions

Serum GA was inversely influenced by fat mass and visceral adipose tissue in Chinese with normal glucose tolerance.     

Dietary Effects on the Composition of Fecal Flora of Rats

A long-term animal feeding experiment was conducted to compare the effect of meat and Wayne laboratory chow diets on the composition of rat fecal flora. Fecal bacteria were enumerated on selective media under both aerobic and anaerobic conditions. Intrarectal administration of N-methyl-N′ -nitro-N-nitro-soguanidine (MNNG) affected the count only on the phenylethylalcohol and veillonella-neomycin agars, whereas a slightly higher number of anaerobes appeared in the feces of rats that were treated with MNNG as compared with those obtained in the feces of untreated rats on the meat diet. In the absence of MNNG, feces of meat-fed rats yielded higher bacterial counts on aerobically incubated MacConkey agar, deoxycholate agar, and Pfizer selective enterococcus agar as well as higher numbers of clostridia on anaerobic egg yolk agar than did feces of rats on the Wayne diet. Feces of the group fed the Wayne diet produced more colonies on aerobic mitis-salivarius agar and lactobacillus agar as well as on anaerobically incubated phenylethylalcohol agar, veillonellaneomycin agar, bifidobacteria agar, fusobacterium (Nissui) agar, and kanamycin-vancomycin blood agar. These differences were consistent throughout the 1-year feeding period.     

Effect of Dietary l-Glutamine on the Hepatotoxic Action of d-Galactosamine in Rats

The protective effect of dietary l-glutamine against the hepatotoxic action of d-galactosamine (GalN) was investigated by model experiments with rats. Rats fed with 20% casein diets containing 10% free amino acids were injected with GalN, and the serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase activities and the hepatic glycogen content were assayed 20 hours after the injection. These enzyme activities in the group fed with the 10% l-glutamine diet for 8 days were lower than those in the groups fed with the control, 10% l-glutamic acid and 10% l-alanine diets for 8 days. The more prolonged the feeding period with the 10% l-glutamine diet was, the more the serum activity levels of such enzymes were decreased. Although neomycin also lowered these enzyme activities, its simultaneous ingestion with neomycin did not show any additive or synergistic effect. The hepatic glycogen content in the 10% glutamine group still remained high after the GalN treatment. It is therefore assumed that the effectiveness of glutamine intake would have been mediated by glycogen metabolism rather than by uridine metabolism.     

Distance Estimation Is Influenced by Encoding Conditions

Background

It is well established that foveating a behaviorally relevant part of the visual field improves localization performance as compared to the situation where the gaze is directed elsewhere. Reduced localization performance in the peripheral encoding conditions has been attributed to an eccentricity-dependent increase in positional uncertainty. It is not known, however, whether and how the foveal and peripheral encoding conditions can influence spatial interval estimation. In this study we compare observers'' estimates of a distance between two co-planar dots in the condition where they foveate the two sample dots and where they fixate a central dot while viewing the sample dots peripherally.

Methodology/Principal Findings

Observers were required to reproduce, after a short delay, a distance between two sample dots based on a stationary reference dot and a movable mouse pointer. When both sample dots are foveated, we find that the distance estimation error is small but consistently increases with the dots-separation size. In comparison, distance judgment in peripheral encoding condition is significantly overestimated for smaller separations and becomes similar to the performance in foveal trials for distances from 10 to 16 degrees.

Conclusions/Significance

Although we find improved accuracy of distance estimation in the foveal condition, the fact that the difference is related to the reduction of the estimation bias present in the peripheral conditon, challenges the simple account of reducing the eccentricity-dependent positional uncertainty. Contrary to this, we present evidence for an explanation in terms of neuronal populations activated by the two sample dots and their inhibitory interactions under different visual encoding conditions. We support our claims with simulations that take into account receptive fields size differences between the two encoding conditions.     

Serum Glycine Is Associated with Regional Body Fat and Insulin Resistance in Functionally-Limited Older Adults

Background

Metabolic profiling may provide insight into biologic mechanisms related to age-related increases in regional adiposity and insulin resistance.

Objectives

The objectives of the current study were to characterize the association between mid-thigh intermuscular and subcutaneous adipose tissue (IMAT, SCAT, respectively) and, abdominal adiposity with the serum metabolite profile, to identify significant metabolites as further associated with the homeostasis model assessment of insulin resistance (HOMA-IR), and, to develop a HOMA-IR associated metabolite predictor set representative of regional adiposity, in 73 functionally-limited (short physical performance battery ≤10; SPPB) older adults (age range, 70–85 y).

Methods

Fasting levels of 181 total metabolites, including amino acids, fatty acids and acylcarnitines were measured with use of an untargeted mass spectrometry-based metabolomic approach. Multivariable-adjusted linear regression was used in all analyses.

Results

Thirty-two, seven and one metabolite(s) were found to be associated with IMAT, abdominal adiposity and, SCAT, respectively, including the amino acid glycine, which was positively associated with SCAT and, negatively associated with both IMAT and abdominal adiposity. Glycine and four metabolites found to be significantly associated with regional adiposity were additionally associated with HOMA-IR. Separate stepwise regression models identified glycine as a HOMA-IR associated marker of both IMAT (model R² = 0.51, p<0.0001) and abdominal adiposity (model R² = 0.41, p<0.0001).

Conclusion

Our findings for a positive association between glycine with SCAT but, a negative association between glycine with IMAT and abdominal adiposity supports the hypothesis that SCAT metabolic processes are different from that found in other fat depots. In addition, because of the significant associations found between glycine with HOMA-IR, IMAT, SCAT and abdominal adiposity, our results suggest glycine as a serum biomarker of both insulin sensitivity and regional fat mass in functionally-limited older adults.     

Deregulation of Hepatic Insulin Sensitivity Induced by Central Lipid Infusion in Rats Is Mediated by Nitric Oxide

Background

Deregulation of hypothalamic fatty acid sensing lead to hepatic insulin-resistance which may partly contribute to further impairment of glucose homeostasis.

Methodology

We investigated here whether hypothalamic nitric oxide (NO) could mediate deleterious peripheral effect of central lipid overload. Thus we infused rats for 24 hours into carotid artery towards brain, either with heparinized triglyceride emulsion (Intralipid, IL) or heparinized saline (control rats).

Principal Findings

Lipids infusion led to hepatic insulin-resistance partly related to a decreased parasympathetic activity in the liver assessed by an increased acetylcholinesterase activity. Hypothalamic nitric oxide synthases (NOS) activities were significantly increased in IL rats, as the catalytically active neuronal NOS (nNOS) dimers compared to controls. This was related to a decrease in expression of protein inhibitor of nNOS (PIN). Effect of IL infusion on deregulated hepatic insulin-sensitivity was reversed by carotid injection of non selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) and also by a selective inhibitor of the nNOS isoform, 7-Nitro-Indazole (7-Ni). In addition, NO donor injection (L-arginine and SNP) within carotid in control rats mimicked lipid effects onto impaired hepatic insulin sensitivity. In parallel we showed that cultured VMH neurons produce NO in response to fatty acid (oleic acid).

Conclusions/Significance

We conclude that cerebral fatty acid overload induces an enhancement of nNOS activity within hypothalamus which is, at least in part, responsible fatty acid increased hepatic glucose production.     

Effects of Dietary D-Psicose on Diurnal Variation in Plasma Glucose and Insulin Concentrations of Rats

The effects of supplemental D-psicose in the diet on diurnal variation in plasma glucose and insulin concentrations were investigated in rats. Forty-eight male Wistar rats were divided into four groups. Each group except for the control group was fed a diet of 5% D-fructose, D-psicose, or psico-rare sugar (3:1 mixture of D-fructose and D-psicose) for 8 weeks. Plasma glucose levels were lower and plasma insulin levels were higher at all times of day in the psicose and psico-rare sugar groups than in the control and fructose groups. Weight gain was significantly lower in the psicose group than in the control and fructose groups. Liver glycogen content, both before and after meals was higher in the psicose group than in the control and fructose groups. These results suggest that supplemental D-psicose can lower plasma glucose levels and reduce body fat accumulation. Hence, D-psicose might be useful in preventing postprandial hyperglycemia in diabetic patients.