The effects of rexinoids and rosiglitazone on body weight and uncoupling protein isoform expression in the Zucker fa/fa rat

Agonists for the retinoid X receptor (RXR), the rexinoids, and the peroxisome proliferator-activated receptor gamma (PPAR γ), the thiazolidinediones, are effective in the treatment of insulin resistance in rodent models by enhancing insulin action and improving glycemic control. In the present study, we compared the effects of rexinoids and a thiazolidinedione on body weight and mitochondrial uncoupling protein (UCP) isoform mRNA expression in the obese Zucker fa/fa rat. Long-term (2 weeks) oral treatment with the rexinoids LG100268 and LG100324 reduced food intake and body weight gain, whereas rosiglitazone (BRL49653) tended to increase both food intake and weight gain. LG100268 and LG100324 increased brown adipose tissue (BAT) UCP-1 mRNA content by 2.7-fold (P < .002) and 3.1-fold (P < .001), respectively, while BRL49653 had no effect on BAT UCP-1 mRNA content. Neither the rexinoids nor the thiazolidinedione had any effect on the level of mRNA encoding UCP-2 and the recently described PPAR γ coactivator-1 (PGC-1). LG100324 increased UCP-3 mRNA content by 3.6-fold (P < .0005) in muscle and 4.3-fold (P < .0002) in white adipose tissue (WAT). LG100268 increased UCP-3 mRNA content in WAT by 2-fold (P < .005) but was without any effect on muscle UCP-3. BRL49653 increased UCP-3 mRNA content by 2.1-fold (P < .005) in muscle and 2.7-fold (P < .003) in WAT. Thus, the rexinoids, but not the thiazolidinedione, have an antiobesity action by reducing food intake, and the increase in UCP-1 mRNA content in BAT may reflect a stimulation of BAT UCP-1 activity.     

Sex differences in postprandial plasma tumor necrosis factor–α, interleukin-6, and C-reactive protein concentrations

Abdominal obesity and insulin resistance are characterized by low-level chronic inflammation most likely implicated in the increased cardiovascular disease risk associated with these conditions. However, not much is known of the acute regulation of circulating inflammatory markers in response to food intake. The aim of this study is to examine changes in inflammatory marker concentrations after the consumption of a high-fat meal in men and women. We measured tumor necrosis factor–α (TNF-α), interleukin-6 (IL-6), and C-reactive protein concentrations in plasma samples collected at 0, 4, and 8 hours after consumption of the meal in 39 men and 41 women. Associations between these variations and physical as well as metabolic variables were then examined. We noted significant increases in plasma IL-6 concentrations at 4 and 8 hours after the meal in men (+34% and +107%, respectively; P < .005 vs 0 hour) and women (+78% and +153%, respectively; P < .0001 vs 0 hour). Postprandial plasma TNF-α concentrations significantly dropped at 4 hours after the high-fat meal in men (−9.5%, P < .0005 vs 0 hour) and women (−5.5%, P < .05 vs 0 hour). Plasma CRP concentrations were not affected by food intake in either men or women. We also found that postprandial plasma concentrations of IL-6 were lower in subjects with a normal glucose tolerance (n = 69) compared with individuals with an impaired glucose tolerance (n = 11). Results of the present study show that consumption of a high-fat meal is associated with a transient reduction in circulating concentrations of TNF-α in both men and women as well as an elevation of plasma IL-6 concentrations that was found to be greater in women than in men.     

Insulin and glucose suppress hepatic glycogenolysis by distinct enzymatic mechanisms

Both insulin and hyperglycemia can effectively suppress hepatic glucose output (HGO). We examined whether insulin and hyperglycemia specifically suppress liver net glycogen breakdown in a rat model in which glycogen is the major source of HGO. We further examined whether insulin and hyperglycemia act by similar or distinct enzymatic mechanisms. HGO, the rate of net glycogen loss, and glycogen phosphorylase and synthase activities were measured in fed, anesthetized rats infused with saline or insulin (7 mU/min/kg) while either maintaining plasma glucose at basal (7.8 ± 0.2 mmol/L, euglycemic clamp [EC]) or at 10 mmol/L above basal (18 ± 0.4 mmol/L, hyperglycemic clamp [HC]). During the basal period, the rate of HGO in each group was comparable to the rate of net glycogen breakdown, averaging 76 ± 9 and 75 ± 5 μmol/min/kg, respectively. Thus glycogen breakdown appeared to be a major source of ongoing HGO. Over the last 60 minutes of the experimental period, the rate of glycogenolysis averaged 69 ± 8 μmol/min/kg in saline-treated rats; this could account for about 80% of the total HGO. During both EC and HC studies, HGO was suppressed (5.5 ± 3 and −3.6 ± 10 μmol/min/kg, respectively; P < .001 for each). Net glycogen breakdown decreased by 50% in EC rats (P < .05) and ceased in HC rats (P < .001). Glycogen synthase was predominantly in the active form in all three experimental groups (87% ± 2%, 89% ± 2%, and 95% ± 3% in saline, EC, and HC rats, respectively). The fraction of glycogen phosphorylase in the active form was similar in saline (41% ± 2%) and EC (40% ± 2%) rats, but lower (23% ± 5%, P < .03) in HC rats. In summary, insulin fully suppresses HGO and partially inhibits net glycogenolysis in vivo without affecting the phosphorylation state of glycogen phosphorylase. Addition of hyperglycemia enhances phosphorylase a to b conversion and fully suppresses net glycogenolysis. Glucose produced by residual glycogenolysis during EC does not reach the systemic circulation and must be disposed of glycolytically in liver.     

Effects of fat supplementation on glycaemic response and gastric emptying in adolescents with Type 1 diabetes

Aims To compare the glycaemic response to meals with different fat content in adolescents with Type 1 diabetes mellitus (T1DM) and to investigate associations with gastric emptying. Methods In this randomized, cross‐over study, paired results were obtained from seven adolescents with T1DM who ingested on different days two meals with the same carbohydrate and protein content, but different fat and energy content (2 and 38 g fat, 320 and 640 kcal, respectively). Paracetamol was mixed into the meals and gastric emptying was estimated by the paracetamol absorption method. All subjects were normoglycaemic and given 7 IU insulin aspart at commencement of ingestion. Postprandial blood samples were taken during 4 h. Results The areas under the curves for plasma glucose and serum paracetamol concentrations were larger after the low‐fat than after the high‐fat meal during the first 2 h (P = 0.047 and P = 0.041, respectively). The difference between meals in time‐to‐peak in glucose and paracetamol concentrations did not reach statistical significance (high‐fat vs. low‐fat meal: 210 min (120–240) vs. 120 min (50–240), P = 0.080 and 120 min (75–180) vs. 60 min (60–120), P = 0.051, respectively). Changes in glucose concentrations correlated with simultaneous changes in paracetamol concentrations (P < 0.001). Conclusions For the first time, we have shown that the initial glycaemic response is reduced after a meal with higher compared with a meal with lower fat content in adolescents with T1DM given a rapid‐acting insulin analogue preprandially. The type and dose of preprandial insulin may need adjustment to the fat content of the meal to reach postprandial normoglycaemia.     

Gastric emptying of solids is markedly delayed when meals are fried

We studied the effect of heat-treated fats on gastric emptying. Eight healthy asymptomatic volunteers (five males; age 28–41 years) ate on different days and in random order two meals identical in contents (pasta, tomato, beef, olive oil, carrots, orange, water; 870 kcal males, 700 kcal females; 47% of calories from carbohydrate, 36% from fat, 17% from protein), but cooked differently (fats fried or not). Ultrasound measurement of antral diameters was used to calculate basal antral section, its maximal dilation after the meal, the time necessary for total emptying, and the percent retention at hourly intervals. No difference was found in basal and maximal antral diameters after the two meals. On the contrary, total gastric emptying was significantly delayed after the fried meal [317.1 (24.12) vs 226.7 (18.4) min, mean (1sem);P0.002]. A significantly greater percentage of maximal antral distension was still present between 120 and 240 min after the fried meal. The glycemic response and hunger feeling were the same after the two meals, whereas there was a longer persistence of satiety and epigastric fullness after the fried meal. In conclusion, gastric emptying can be influenced not only by the meal content, but also by the way it is cooked.This work was supported by grant 93.00599.PF41 from the Italian National Research Council (CNR)-Targeted Project Prevention and Control of Disease Factors, Subproject Alimentation.     

Comparison of Inulin and Lactulose as Reference Standards in the Breath Hydrogen Test Assessment of Carbohydrate Malabsorption in Patients with Chronic Pancreatic Exocrine Insufficiency

Although often used as a reference standard in the breath hydrogen test (BHT), lactulose fermentation produces more hydrogen, compared to starch, and may therefore not be ideal. This study compares inulin with lactulose as reference standard in the study of carbohydrate malabsorption. Seventeen patients with malabsorption due to chronic pancreatitis and 15 normal controls were studied. Following overnight fasts, BHTs were performed after ingesting 10 g lactulose, 10 g inulin, and 200 g (16 g highly resistant starch) maize meal. Lactulose fermentation produced significantly more hydrogen than inulin in patients with malabsorption (97± 20 vs 45± 22 ppm ⋅ hr; P < 0.05) and controls (43 ± 18 vs 21 ± 10 ppm ⋅ hr; P < 0.05). Patients produced more hydrogen than controls with both standards (lactulose, 97 ± 20 vs 43 ± 18 ppm ⋅ hr, P < 0.05; inulin 45 ± 22 vs 21 ± 10 ppm ⋅ hrs; P < 0.05), suggesting adaptation of the colonic flora. Calculated CHO malabsorption was 2.5 ± 0.8 vs 5.2 ± 3.8 g with lactulose and 5.2 ± 3.1 vs 11.2 ± 9.6 g with inulin as standards in controls and patients, respectively (P < 0.05). Lactulose produces more breath hydrogen than inulin. Calculation of CHO malabsorption using these standards is therefore not comparable.This work was supported by a grant from the South African Medical Research Council.     

Effect of moderate weight loss on hepatic,pancreatic and visceral lipids in obese subjects

Objective:

To compare the effects of weight loss on visceral and subcutaneous abdominal fat, liver and pancreas lipid content and to test the effects of these changes on metabolic improvement observed after weight loss.

Design:

Weight-loss program designed to achieve a loss of 7–10% of the initial weight.

Subjects:

24 obese subjects (13 males and 11 females) with age ranging from 26 to 69 years and body mass index (BMI) 30.2–50.5 kg m⁻². Measurements: weight, BMI, waist circumference, body composition as assessed by dual-energy X-ray absorptiometry, metabolic variables, leptin, adiponectin, visceral and subcutaneous abdominal fat, liver and pancreas lipid content as assessed by magnetic resonance were evaluated before and after weight loss achieved by hypocaloric diet.

Results:

After a mean body weight decrease of 8.9%, BMI, waist circumference, fat mass, all metabolic variables, homeostasis model assessment of insulin resistance (HOMA), alanine amino transferase, gamma glutamyl transpeptidase, high-sensitivity C-reactive protein (hs-CRP) and leptin, but not adiponectin and high-density lipoprotein-cholesterol, significantly decreased (all P<0.01). Visceral and subcutaneos abdominal fat, liver and pancreas lipid content significantly decreased (all P<0.01). Percent changes in liver lipid content were greater (84.1±3%) than those in lipid pancreas content (42.3±29%) and visceral abdominal fat (31.9±15.6%). After weight loss, percentage of subjects with liver steatosis decreased from 75 to 12.5%. Insulin resistance improvement was predicted by changes in liver lipid content independently of changes in visceral fat, pancreas lipid content, systemic inflammation, leptin and gender.

Conclusion:

Moderate weight loss determines significant decline in visceral abdominal fat, lipid content in liver and pancreas. Reduction of liver lipid content was greater than that of pancreas lipid content and visceral fat loss. Liver lipid content is the strongest predictor of insulin resistance improvement after weight loss.     

Effect of Omega-3 Fatty Acid Supplementation on the Postprandial Metabolism of Apolipoprotein(a) in Familial Hypercholesterolemia

Aim: Lipoprotein(a) (Lp(a)) is a low-density lipoprotein-like particle containing apolipoprotein(a) (apo(a)) that increases the risk of atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH). Postprandial redistribution of apo(a) protein from Lp(a) to triglyceride-rich lipoproteins (TRLs) may also increase the atherogenicity of TRL particles. Omega-3 fatty acid (ω3FA) supplementation improves postprandial TRL metabolism in FH subjects. However, its effect on postprandial apo(a) metabolism has yet to be investigated. Methods: We carried out an 8-week open-label, randomized, crossover trial to test the effect of ω3FA supplementation (4 g/day) on postprandial apo(a) responses in FH patients following ingestion of an oral fat load. Postprandial plasma total and TRL-apo(a) concentrations were measured by liquid chromatography with tandem mass spectrometry, and the corresponding areas under the curve (AUCs) (0–10h) were determined using the trapezium rule. Results: Compared with no ω3FA treatment, ω3FA supplementation significantly lowered the concentrations of postprandial TRL-apo(a) at 0.5 (−17.9%), 1 (−18.7%), 2 (−32.6%), and 3 h (−19.2%) (P＜0.05 for all). Postprandial TRL-apo(a) AUC was significantly reduced with ω3FA by 14.8% (P＜0.05). By contrast, ω3FA had no significant effect on the total AUCs of apo(a), apoC-III, and apoE (P＞0.05 for all). The decrease in postprandial TRL-apo(a) AUC was significantly associated with changes in the AUC of triglycerides (r=0.600;P＜0.01) and apoB-48 (r=0.616;P＜0.01). Conclusions: Supplementation with ω3FA reduces postprandial TRL-apo(a) response to a fat meal in FH patients; this novel metabolic effect of ω3FA may have implications on decreasing the risk of ASCVD in patients with FH, especially in those with elevated plasma triglyceride and Lp(a) concentrations. However, the clinical implications of these metabolic findings require further evaluation in outcome or surrogate endpoint trials.     

Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects

Objectives:

Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet and seems to account for the protective effect against cardiovascular disease. However, the underlying mechanism is still elusive.

Design:

We tested the effect of EVOO, added to Mediterranean-type meal, on post-prandial glycemic and lipid profile.

Subjects:

Post-prandial glycemic and lipid profile were investigated in 25 healthy subjects who were randomly allocated in a cross-over design to a Mediterranean-type meal added with or without 10 g EVOO (first study), or Mediterranean-type meal with EVOO (10 g) or corn oil (10 g; second study). Glycemic profile, which included glucose, insulin, dipeptidyl-peptidase-4 (DPP-4) protein and activity, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and lipid profile, which included, low-density lipoprotein (LDL) cholesterol (LDL-C), oxidized LDL (ox-LDL), triglycerides and high-density lipoprotein (HDL) cholesterol (HDL-C), were analyzed before and 2 h after the meal.

Results:

In the first study, 2 h after meal, subjects who assumed a meal with EVOO had significantly lower blood glucose (P<0.001), DPP-4 protein (P<0.001) and activity (P<0.001), LDL-C (P<0.001) and ox-LDL (P<0.001) and higher insulin (P<0.05), GLP-1 (P<0.001) and GIP (P<0.05) compared with those without EVOO. The second study showed that compared with corn oil, EVOO improved both glycemic and lipid profile. Thus, a significantly smaller increase of glucose (P<0.05), DPP4 protein (P<0.001) and activity (P<0.05) and higher increase of insulin (P<0.001) and GLP-1 (P<0.001) were observed. Furthermore, compared with corn oil, EVOO showed a significantly less increase of LDL-C (P<0.05) and ox-LDL (P<0.001).

Conclusions:

We report for the first time that EVOO improves post-prandial glucose and LDL-C, an effect that may account for the antiatherosclerotic effect of the Mediterranean diet.     

Role of nutrient fat and cholecystokinin in regulation of gallbladder emptying in man

Postprandial gallbladder contraction is mainly regulated by cholecystokinin (CCK), but little is known about the dose-response relationship between CCK release and gallbladder contraction, in particular after meals with differing fat content. Decreased postprandial gallbladder emptying has been suggested to play a major role in the development of gallstones in man, and dietary factors may therefore be important in the pathogenesis of gallbladder stasis. We studied, in a randomized order, the effect of three isocaloric meals (250 ml) with identical osmolality on CCK release and gallbladder contraction in six healthy volunteers: (1) a pure fat meal (25 g triglycerides); (2) a mixed meal containing fat (8 g, 29% of caloric content), protein (10 g, 17%), and dextrose (32 g, 54%); and (3) a fat-free meal containing albumin (25 g, 46%) and dextrose (32 g, 54%). Gallbladder volumes and antral cross-sectional areas were determined by ultrasonography and plasma CCK and PP levels by RIA. The pure fat meal caused the highest CCK release (187±27; mean ±sem) and maximal (>85% of fasting volume) gallbladder contraction (3172±361; AUC) as compared to the other two meals (P<0.05). The mixed and the fat-free meal caused similarly low (<50% of fasting volume) gallbladder contraction (6052±342 and 6134±500, respectively), although they induced markedly different CCK levels (157±12 and 87±13, respectively;P<0.05). Gastric emptying rates were similar for all meals (18,500±3300, 18,600±2700 and 19,800±3100, respectively). The results of this study suggest that CCK plays a major role in the stimulation of gallbladder contraction but that other factors besides CCK are implied when fat-free or low-fat meals are ingested. Furthermore, our findings suggest that a fat intake of 25 g induces maximal gallbladder contraction and may thus prevent an understimulation of gallbladder contraction and the formation of gallbladder stones.     

Influence of orlistat on the regulation of gallbladder contraction in man

Orlistat (tetrahydrolipstatin) is a potent inhibitor of gastric and pancreatic lipase activity causing a diminution of free fatty acids in the intestinal lumen. The release of cholecystokinin (CCK) critically depends on the presence of free fatty acids in the small intestine. Postprandial CCK release and gallbladder contraction might be decreased by orlistat, potentially resulting in an increased risk of gallstone formation. In this double-blind, placebo-controlled, six-way crossover study, six healthy volunteers ingested in a randomized order three isocaloric test meals (250 ml) of identical osmolality with either orlistat (200 mg) or placebo: (a) a pure-fat meal (25 g triglycerides), (b) a mixed meal containing fat (8 g; 29% of caloric content), protein (10 g; 17%), and dextrose (32 g; 54%), and (c) a fat-free meal containing albumin (25 g; 46%) and dextrose (32 g; 54%). Gallbladder volumes were determined by ultrasonography, and plasma CCK, pancreatic polypeptide and gastrin levels by RIA. Gallbladder contraction (AUC, % × 90 min; difference of means ± 95% CI) in subjects receiving orlistat or placebo did not significantly differ after intake of the pure-fat meal (443 ± 1174), the mixed meal (313 ± 1170), or the fat-free-meal (–760 ± 1180). The release of CCK (AUC; pM × 90 min; difference of means ± 95% CI) was not different between orlistat and placebo after ingestion of the pure-fat meal (–18 ± 64), the mixed meal (–45 ± 62), and the fat-free meal (27 ± 63). Likewise, the release of pancreatic polypeptide and gastrin was similar after intake of the meals with either orlistat or placebo. A single dose of orlistat did not reduce gallbladder motility after ingestion of meals with differing fat contents. The safety of long-term treatment with orlistat with respect to gallstone formation remains to be determined.     

Stearic acid content of abdominal adipose tissues in obese women

Objective:

Subcutaneous (SC) adipose tissue stearic acid (18:0) content and stearoyl-CoA desaturase-1 (SCD1)-mediated production of oleic acid (18:1) have been suggested to be altered in obesity. The objective of our study was to examine abdominal adipose tissue fatty acid content and SCD1 mRNA/protein level in women.

Subjects and methods:

Fatty acid content was determined by capillary gas chromatography in SC and omental (OM) fat tissues from two subgroups of 10 women with either small or large OM adipocytes. Samples from 10 additional women were used to measure SCD1 mRNA and protein expression, total extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 protein as well as insulin receptor (IR) expression levels.

Results:

OM fat 18:0 content was significantly lower in women with large OM adipocytes compared with women who had similar adiposity, but small OM adipocytes (2.37±0.45 vs 2.75±0.30 mg per 100 g adipose tissue, respectively, P⩽0.05). OM fat 18:0 content was negatively related to the visceral adipose tissue area (r=−0.44, P=0.05) and serum triglyceride levels (r=−0.56, P<0.05), while SC fat 18:0 content was negatively correlated with total body fat mass (BFM) (r=−0.48, P<0.05) and fasting insulin concentration (r=−0.73, P<0.005). SC adipose tissue desaturation index (18:1/18:0), SCD1 expression and protein levels were positively correlated with BFM. Moreover, obese women were characterized by a reduced OM/SC ratio of SCD1 mRNA and protein levels. A similar pattern was observed for ERK1/2 and IR expression.

Conclusion:

The presence of large adipocytes and increased adipose mass in a given fat compartment is related to reduced 18:0 content and increased desaturation index in women, independently of dietary fat intake. The depot-specific difference in ERK1/2 expression and activation, as well as in SCD1 and IR expression in obese women is consistent with the hypothesis that they may predominantly develop SC fat, which could in turn help protect from metabolic disorders.     

Effect of the introduction of dietary sucrose on metabolic control in children and adolescents with type I diabetes

The effect of sucrose in the diet of children and adolescents with type I diabetes on long-term metabolic control was studied. For a mean observation period of 83 (range 42–127) days, a diet containing 5% of total calories as refined sugar was recommended to 11 children (group A, mean age 15.0, SD 5.4 years), while another 13 children remained on their usual sucrose-free diet (group B, mean age 16.0, SD 5.7 years). The mean observation period in this group was 77 (41–103) days. All children had a dietary assessment at baseline and at follow up using a 7-day food record. At baseline, sucrose intake as a proportion of total daily calories was similar in the two groups (group A 1.4, SD 1.9% vs group B 2.0, SD 2.3%;P=0.5). At follow-up, sucrose intake increased significantly in group A (5.1, SD 2.5%;P=0.0008), but not in group B (2.7, SD 3.3%;P=0.5). Metabolic control assessed by haemoglobin level (HbA_1c) was not different between the groups at baseline (group A 8.5, SD 1.2 vs group B 8.8, SD 1.8%;P=0.7) nor at follow-up (9.1, SD 1.4 vs 9.0, SD 2.5%;P=0.9). Within group A, the individual change in HbA_1c correlated with the individual change in sucrose intake (r=0.61,P=0.05), this correlation being strongly influenced by two individuals with an increase in sucrose consumption substantially exceeding 5%. Percentage intake of protein, carbohydrate and fat did not change significantly. Fibre consumption decreased with increasing consumption of sucrose in group A (r=–0.75,P=0.007). It is concluded that the introduction of sucrose in the diet of children and adolescents with type I diabetes up to 5% of the daily total calories has no negative effect on metabolic control but reduces the amount of fibre in the diet. Higher amounts of sucrose might have negative effects on metabolic control.     

Field investigation on the repellent activity of some aromatic plants by traditional means against Anopheles arabiensis and An. pharoensis (Diptera: Culicidae) around Koka, central Ethiopia

A study was undertaken to evaluate the impact of traditional application methods of mosquito repellent plants in the reduction of the human–vector contact of malaria vectors in central Ethiopia. The plants (Corymbia citriodora, Eucalyptus camaldulensis, Ocimum suave and Ocimum basilicum) were tested by thermal expulsion and direct burning on traditional stoves in the field against two important malaria vectors in Ethiopia (Anopheles arabiensis and An. pharoensis). A Latin-square design was applied for randomly assigning the treatment plants and control to experimental houses over different nights. The percentage repellency of each candidate plant by both application methods was estimated from the catches of mosquitoes in the treatment and control houses. On direct burning of the plants, O. basilicum showed the highest percentage repellency (73.11%, P < 0.001) and E. camaldulensis the least repellency (65.29%, P < 0.001) against An. arabiensis. By the same method of application, C. citriodora on the other hand gave the highest repellency (72.87%, P < 0.001) while E. camaldulensis was still the least repellent plant (66.60%, P < 0.001) against An. pharoensis. On thermal expulsion, C. citriodora exhibited the highest repellency (78.69%, P < 0.001) while E. camaldulensis was the lowest repellent plant (71.91%, P < 0.001) against An. arabiensis. Against An. pharoensis, C. citriodora gave the highest repellency (72.9%, P < 0.001) while E. camaldulensis still gave the least repellency (72.2%, P < 0.001) on the same method of application. All the tested plants by both methods of application gave partial but significant protection (>65%) against the house-entry and biting of two important malaria vectors in Ethiopia, and thus have a potential to be used at least as supplements to other control methods. However, feasibility and actual impact on disease transmission need to be known on these and other potentially useful plants.     

The response of serum sialic acid and other acute phase reactants to an oral fat load in healthy humans

Background: Elevated serum total sialic acid (TSA) has been shown to be associated with increased cardiovascular mortality. It has been postulated that atherogenesis is a postprandial phenomenon. We tested the hypothesis that serum TSA and other acute phase proteins, namely C-reactive protein (CRP) and fibrinogen, may be related to the postprandial state. Methods: Ten healthy male subjects, aged 24–48 years, were fed 62.5 g of total fat (saturates 12 g, monounsaturates 35.3 g and polyunsaturates 12.5 g) in the form of strawberry flavoured Calogen. Venous blood was sampled hourly for 5 h. Concentrations of serum triglyceride, TSA and acute phase proteins were measured. Results: Serum triglyceride concentration increased postprandially, peaking at 240 min. Serum CRP and plasma fibrinogen did not significantly increase after the oral fat load. However, serum TSA did increase from baseline (0.599±0.051 g/l) in response to the oral fat load, peaking at 120 min post-oral fat load (0.633±0.066 g/l, P<0.02). There was a significant correlation between serum TSA and plasma fibrinogen at baseline (ρ=0.62, P=0.05) but not for serum CRP (ρ=−0.22) or triglyceride (ρ=0.21). Conclusions: We conclude that serum TSA increases postprandially and this finding gives further insight as to why the former is considered to be a cardiovascular risk factor.     

Effect of Calories and Fat on Postprandial Gastro-oesophageal Reflux

Background: Gastro-oesophageal reflux (GOR) is commonly considered to be worsened by fatty food, but it has recently been shown that changing the fat content of equicaloric meals has no effect on GOR over a 3-h postprandial period. Our aims were to verify this finding over a longer postprandial period and test the hypothesis that increasing the caloric content of balanced meals increases GOR. Methods: Thirteen healthy subjects (6 men) aged 19-31 years underwent 6-h oesophageal pH monitoring after 3 solid/liquid meals of the same volume and osmolarity eaten on separate days in a randomized order: a) high fat (58% fat) 2.8 MJ; b) balanced (23% fat) 2.8 MJ; and c) balanced low calorie (25% fat) 1.6 MJ. Results: The mean percentage of time at pH < 4 and the mean number of reflux episodes after the balanced 2.8 MJ meal (3.0% and 11.5, respectively) were higher ( P < 0.05) than after the balanced 1.6 MJ meal (1.6% and 7.2) and similar to those after the equicaloric (2.8 MJ) high-fat meal (2.5% and 9.3). Acid clearance time was similar after all three meals. Conclusions: Our data suggest that advice on dietary habits in patients with GOR disease should be concentrated on decreasing the caloric load of meals rather than their fat content.     

Circulating sCD36 is associated with unhealthy fat distribution and elevated circulating triglycerides in morbidly obese individuals

Background:

The recently identified circulating sCD36 has been proposed to reflect tissue CD36 expression, and is upregulated in case of obesity, insulin resistance and hepatic steatosis. The aim of this study was to explore the effect of weight loss secondary to bariatric surgery in relation to sCD36 among morbidly obese individuals. Furthermore, we investigated the levels of sCD36 in relation to obesity-related metabolic complications, low-grade inflammation and fat distribution.

Methods:

Twenty morbidly obese individuals (body mass index (BMI) 43.0±5.4 kg m⁻²) with a referral to Roux-en-Y gastric bypass were included. Anthropometric measurements and fasting blood samples were collected at a preoperative baseline visit and 3 months after surgery. sCD36 was measured by an in-house assay, whereas insulin sensitivity and the hepatic fat accumulation were estimated by the homeostasis model assessment (HOMA-%S) and liver fat percentage (LF%), respectively.

Results:

Postoperatively, BMI was reduced by 20% to 34.3±5.2 kg m⁻² (P<0.001). sCD36 was reduced by 31% (P=0.001) and improvements were observed in the amount of fat mass (P<0.001), truncal fat mass (P<0.001), circulating triglycerides (P=0.001), HOMA-%S (P=0.007), LF% (P=0.001) and the inflammatory marker high-sensitive C-reactive protein (P=0.005). sCD36 correlated with triglycerides (ρ=0.523, P=0.001) and truncal fat mass (ρ=0.357, P=0.026), and triglycerides were found to be an independent predictor of sCD36. At baseline, participants with the metabolic syndrome had a higher LF% and higher levels of the inflammatory biomarker YKL-40 (P=0.003 and P=0.014) as well as a tendency towards higher levels of sCD36.

Conclusion:

sCD36 was reduced by weight loss and associated with an unhealthy fat accumulation and circulating triglycerides, which support the proposed role of sCD36 as a biochemical marker of obesity-related metabolic complications and risks.     

Ketosis resistance in the male offspring of protein-malnourished rat dams

Plasma β-hydroxybutyrate concentrations were measured in the offspring of rats that were fed either a control (20% protein) diet or low-protein (8% protein) diet during pregnancy and lactation. Low-protein offspring had significantly lower plasma β-hydroxybutyrate compared with controls in the fed state (P < .04) and after fasting for 24 hours (P < .001) and 48 hours (P < .04). There were no differences in blood glucose, acetoacetate, plasma glucagon, cholesterol, or glycerol between control and low-protein offspring. However, plasma nonesterified fatty acids (NEFAs) were significantly higher in low-protein offspring in the fed state (P < .05). In contrast, plasma triglycerides and insulin were significantly lower in low-protein offspring compared with controls when fed (P < .001) and after a 24-hour fast (P < .001). These results suggest that poor maternal and early postnatal nutrition can have long-term effects on ketone body metabolism in the offspring during adulthood. This apparent ketosis resistance is similar to that observed in some forms of human diabetes.     

Effect of increasing the fat content but not the energy load of a meal on gastro-oesophageal reflux and lower oesophageal sphincter motor function

Background—Although fatty foods are commonlyconsidered detrimental in patients with reflux disease, no objectivedata exist that substantiate this belief.
Aims—To investigate the effect of fat ongastro-oesophageal reflux and lower oesophageal sphincter (LOS) motor activity.
Subjects—Thirteen healthy subjects and 14 patients with reflux disease.
Methods—Oesophageal pH, LOS, and oesophagealpressures were recorded for 180 minutes after a high fat (52% fat) anda balanced (24% fat) meal (both 3.18 MJ) on two different occasions.Eight controls and seven patients were studied in the recumbentposition and the others in the sitting position.
Results—The percentage of time at pH less than 4 and the rate of reflux episodes were higher (p<0.01) in the patientsthan in the healthy subjects (mean 14.1% versus 1.7% and 4.4/h versus 0.8/h respectively), as was the percentage of transient LOS relaxations associated with reflux (62% versus 32%, p<0.01). The high fat mealdid not increase the rate of reflux episodes nor exposure tooesophageal acid in either group regardless of body posture.The rate oftransient LOS relaxations, their association with reflux, and basal LOSpressure were also unaffected.
Conclusions—Increasing fat intake does not affectgastro-oesophageal reflux or oesophagogastric competence for at leastthree hours after a meal.

Keywords:oesophagus; oesophagogastric junction; gastro-oesophageal reflux; fat