Biomedical subjects

Robert H J Bandsma

Publications and source records attributed to Robert H J Bandsma.

6 recordsLinked to original sources

PubMed2004

Cholesterol synthesis and de novo lipogenesis in premature infants determined by mass isotopomer distribution analysis.

Premature infants change from placental supply of mainly carbohydrates to an enteral supply of mainly lipids earlier in their development than term infants. The metabolic consequences hereof are not known but might have long-lasting health effects. In fact, knowledge of lipid metabolism in premature infants is very limited. We have quantified de novo lipogenesis and cholesterogenesis on d 3 of life in seven premature infants (birth weight, 1319 +/- 417 g; gestational age, 30 +/- 2 wk). For comparison, five healthy adult subjects were also studied. All subjects received a 12-h [1-(13)C] acetate infusion, followed by mass isotopomer distribution analysis (MIDA) on lipoprotein-palmitate and plasma unesterified cholesterol. The fraction of lipoprotein-palmitate synthesized at the end of the infusion period was 5.4 +/- 3.9% in infants, which was in the same range as found in adult subjects on a normal diet, suggesting that hepatic de novo lipogenesis is not a major contributor to fat accumulation in these premature neonates. The fractional contribution of newly synthesized cholesterol to plasma unesterified cholesterol was 7.4 +/- 1.3% after a 12-h infusion. The calculated rate of endogenous cholesterol synthesis was 31 +/- 7 mg/kg/d, a value approximately three times higher than that found in adult subjects (10 +/- 6 mg/kg/d). These results indicate that the cholesterol-synthesizing machinery is well developed in premature infants.

Acetates↗

PubMed2004

Low-fat, high-carbohydrate and high-fat, low-carbohydrate diets decrease primary bile acid synthesis in humans.

BACKGROUND: Dietary fat content influences bile salt metabolism, but quantitative data from controlled studies in humans are scarce. OBJECTIVE: The objective of the study was to establish the effect of dietary fat content on the metabolism of primary bile salts. DESIGN: The effects of eucaloric extremely low-fat (0%), intermediate-fat (41%; control diet), and extremely high-fat (83%) diets on kinetic values of cholate and chenodeoxycholate metabolism were determined after 11 d by using stable isotope dilution in 6 healthy men. All diets contained identical amounts of cholesterol. RESULTS: The total primary bile salt pool size was not significantly affected by dietary fat content, although the chenodeoxycholate pool was significantly higher during the low-fat diet. Fractional turnover rates of both primary bile salts were 30-50% lower during the low- and high-fat diets than during the control diet. Total hepatic bile salt synthesis was approximately 30% lower during both the high- and low-fat diets, but synthesis rates of the 2 primary bile salts were differentially affected. The molar ratio of cholate to total bile salt synthesis increased from 0.50 +/- 0.05 ( +/- SD) to 0.59 +/- 0.05 and 0.66 +/- 0.04 with increasing fat intake, whereas the molar ratio of chenodeoxycholate to total bile salt synthesis decreased from 0.50 +/- 0.05 to 0.41 +/- 0.05 and 0.34 +/- 0.04. The relative concentration of deoxycholate in plasma increased during the low-fat period, which indicated increased absorption from the colon. CONCLUSIONS: Both low- and high-fat diets reduce the synthesis and turnover rates of primary bile salts in humans, although probably through different mechanisms, and consequently they affect the removal of cholesterol from the body.

Adult↗

PubMed2003

Hepatic de novo synthesis of glucose 6-phosphate is not affected in peroxisome proliferator-activated receptor alpha-deficient mice but is preferentially directed toward hepatic glycogen stores after a short term fast.

Apart from impaired beta-oxidation, Pparalpha-deficient (Pparalpha(-/-)) mice suffer from hypoglycemia during prolonged fasting, suggesting alterations in hepatic glucose metabolism. We compared hepatic glucose metabolism in vivo in wild type (WT) and Pparalpha(-/-) mice after a short term fast, applying novel isotopic methods. After a 9-h fast, mice were infused with [U-(13)C]glucose, [2-(13)C]glycerol, [1-(2)H]galactose, and paracetamol for 6 h, and blood and urine was collected in timed intervals. Plasma glucose concentrations remained constant and were not different between the groups. Hepatic glycogen content was 69 +/- 11 and 90 +/- 31 microM/g liver after 15 h of fasting in WT and Pparalpha(-/-) mice, respectively. The gluconeogenic flux toward glucose 6-phosphate was not different between the groups (i.e. 157 +/- 9 and 153 +/- 9 microM/kg/min in WT and Pparalpha(-/-) mice, respectively). The gluconeogenic flux toward plasma glucose, however, was decreased in PPARalpha(-/-) mice (i.e. 142 +/- 9 versus 124 +/- 13 microM/kg/min) (p < 0.05), accounting for the observed decrease (-15%) in hepatic glucose production in Pparalpha(-/-) mice. Expression of the gene encoding glucose-6-phosphate hydrolase (G6ph) was lower in the PPARalpha(-/-) mice compared with WT mice. In conclusion, Pparalpha(-/-) mice were able to maintain a normal total gluconeogenic flux to glucose 6-phosphate during moderate fasting, despite their inability to up-regulate beta-oxidation. However, this gluconeogenic flux was directed more toward glycogen, leading to a decreased hepatic glucose output. This was associated with a down-regulation of the expression of G6ph in PPARalpha-deficient mice.

Animals↗

PubMed2003

Hepatic VLDL production in ob/ob mice is not stimulated by massive de novo lipogenesis but is less sensitive to the suppressive effects of insulin.

Type 2 diabetes in humans is associated with increased de novo lipogenesis (DNL), increased fatty acid (FA) fluxes, decreased FA oxidation, and hepatic steatosis. In this condition, VLDL production is increased and resistant to suppressive effects of insulin. The relationships between hepatic FA metabolism, steatosis, and VLDL production are incompletely understood. We investigated VLDL-triglyceride and -apolipoprotein (apo)-B production in relation to DNL and insulin sensitivity in female ob/ob mice. Hepatic triglyceride (5-fold) and cholesteryl ester (15-fold) contents were increased in ob/ob mice compared with lean controls. Hepatic DNL was increased approximately 10-fold in ob/ob mice, whereas hepatic cholesterol synthesis was not affected. Basal rates of hepatic VLDL-triglyceride and -apoB100 production were similar between the groups. Hyperinsulinemic clamping reduced VLDL-triglyceride and -apoB100 production rates by approximately 60% and approximately 75%, respectively, in lean mice but only by approximately 20% and approximately 20%, respectively, in ob/ob mice. No differences in hepatic expression of genes encoding apoB and microsomal triglyceride transfer protein were found. Hepatic expression and protein phosphorylation of insulin receptor and insulin receptor substrate isoforms were reduced in ob/ob mice. Thus, strongly induced hepatic DNL is not associated with increased VLDL production in ob/ob mice, possibly related to differential hepatic zonation of apoB synthesis (periportal) and lipid accumulation (perivenous) and/or relatively low rates of cholesterogenesis. Insulin is unable to effectively suppress VLDL-triglyceride production in ob/ob mice, presumably because of impaired insulin signaling.

Adipose Tissue↗

PubMed2002

Disturbed lipid metabolism in glycogen storage disease type 1.

UNLABELLED: Glycogen storage disease type 1 (GSD1) is an inborn error of metabolism caused by deficiency of glucose-6-phosphatase, the enzyme catalysing the conversion of glucose-6-phosphate (G6P) to glucose. GSD1 is associated with severe hyperlipidaemia and hepatic steatosis. The underlying mechanisms responsible for these abnormalities in lipid metabolism are only partly known. This review summarises data available on hyperlipidaemia and steatosis in GSD1 and postulates new hypotheses for unresolved issues. Evidence indicates that lipid clearance from the blood compartment is decreased in GSD1. Furthermore, in two GSD1a patients synthesis of palmitate, an indicator of de novo lipogenesis, and cholesterol were found to be increased 40-fold and 7-fold, respectively. Elevated hepatic G6P levels may play a regulatory role in lipid synthesis via activation of transcription of lipogenic genes. In addition, accelerated glycolysis will supply acetyl-CoA molecules required for lipogenesis. It is as yet unclear whether hepatic secretion of lipids in the form of very low density lipoprotein-triglycerides (VLDL-TG) is altered in GSD1 patients: we recently found unaffected VLDL-TG secretion rates in an acute animal model of GSD1b. Hepatic steatosis, which is invariably present in GSD1 is probably mainly caused by an increased free fatty acid flux from adipose tissue to the liver and, to a limited extent, by increased de novo lipogenesis. CONCLUSION: future studies, using novel stable isotope methodologies, are warranted to further clarify the disturbances in lipid and lipoprotein metabolism in glycogen storage disease type 1 and the role of glucose-6-phosphate herein.

Animals↗

PubMed2002

Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a.

We describe 2 patients with glycogen storage disease type 1a and severe hyperlipidemia without premature atherosclerosis. Susceptibility of low-density lipoproteins to oxidation was decreased, possibly related to the ~40-fold increase in palmitate synthesis altering lipoprotein saturated fatty acid contents. These findings are potentially relevant for antihyperlipidemic treatment in patients with glycogen storage disease type 1a.

Adult↗