Substrate delivery as a determinant of hepatic apoB secretion.

Sniderman, Allan D.; Cianflone, Katherine

doi:10.1161/01.atv.13.5.629

Cited by 187 publications

(81 citation statements)

References 91 publications

(40 reference statements)

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“…33 Furthermore, an effect of this kind would have delayed peak TAG concentrations during the walking trials Ð something we did not observe. There could be decreased hepatic VLDL-TAG secretion during the walking trials but plasma concentrations of NEFA and insulin, both important in¯uences on this, 34 did not differ between trials.…”

Section: Discussionmentioning

confidence: 83%

Different patterns of brisk walking are equally effective in decreasing postprandial lipaemia

2000

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OBJECTIVE: To compare the effects of different patterns of brisk walking on day-long plasma triacylglycerol concentrations in sedentary adults. DESIGN: A three-trial, repeated measures design in which subjects were studied in the fasted state and throughout a day during which they consumed three standardized, mixed meals. On different occasions, subjects undertook no exercise (control), walked briskly for 10 min before each meal (short walks) or walked briskly for 30 min before breakfast (long walk). SUBJECTS: Seven postmenopausal sedentary women and three sedentary men aged between 34 and 66 y, with body mass index between 24 and 35 kgam 2 . MEASUREMENTS: Plasma concentrations of triacylglycerol, non-esteri®ed fatty acids, glucose and insulin, metabolic rate and whole-body substrate oxidation in the fasted state and at hourly intervals for 3 h after each meal. RESULTS: Postprandial plasma triacylglycerol concentrations were lower (P 0.009) during the walking trials than during the control trial (average values: control 2.08 AE 0.28 mmolal; short walks 1.83 AE 0.22 mmolal; long walk 1.84 AE 0.22 mmolal (mean AE s.e.) but did not differ between the two patterns of walking. The difference between control and walking trials increased as successive meals were consumed (interaction of trialÂmeal P 0.03). Plasma triacylglycerol concentration increased during the 3 h after breakfast, changed little after lunch and decreased after the evening meal (interaction of mealÂtime P 0.001). When both walking trials were treated as one condition, walking increased postprandial fat oxidation (average values: control, 0.066 AE 0.009 gamin; walking 0.074 AE 0.008 gamin; P`0.01). CONCLUSIONS: Thirty minutes of brisk walking, undertaken in one session or accumulated throughout a day, reduces postprandial plasma triacylglycerol concentrations and increases fat oxidation.

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Section: Discussionmentioning

confidence: 83%

Different patterns of brisk walking are equally effective in decreasing postprandial lipaemia

2000

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“…There is no evidence at present as to whether distinct TAG pools are preferentially utilized for the ' first ' and ' second ' step phases of incorporation of TAG into the hydrophobic core of VLDL. If they were to be so used, then the existence of separate routes for TAG secretion would enable control to be exerted on the number and size of the secreted particles, and thus allow these parameters to be differentially affected by the supply of fatty acid and carbohydrate substrates to the liver [130,131]. Insulin is known to decrease the availability of apoB for secretion by increasing the rate of early degradation of the newly synthesized protein (see [132]).…”

Section: Figure 4 Dual Routes May Be Involved In the Incorporation Ofmentioning

confidence: 99%

“…Insulinenhanced degradation only affects a proportion of total apoB and appears to have different characteristics from constitutive degradation [113,140]. However, it is not known whether it is the availability of apoB that determines the fraction of TAG that is channelled towards secretion, or vice versa ; evidently increases in TAG secretion can occur in the absence of any increase in apoB secretion [130]. From experiments conducted on cultured hepatocytes obtained from fed or starved rats, Davis et al [171] concluded that the availability of apoB %) , which is the major B apoprotein in rat liver, determines the rate of TAG secretion.…”

Section: Partitioning Of Tag Between Secretion and Retention In The Lmentioning

confidence: 99%

Role of insulin in hepatic fatty acid partitioning: emerging concepts

Zammit

1996

Biochemical Journal

114

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“…In vitro and in vivo studies have established that increased delivery of NEFA or uptake of triglyceriderich remnants to the liver will cause the secretion rate of VLDL particles to increase [21,22]. An increased secretion rate of VLDL will result in the increased generation of LDL particles.…”

Section: Consequences Of An Impaired Asp Pathwaymentioning

confidence: 99%

The pathogenetic role of impaired fatty acid trapping by adipocytes in generating the pleiotropic features of hyperapoB

Sniderman¹,

Cianflone²,

Frayn

1997

Diabetologia

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HyperapoB is the commonest dyslipoproteinaemia associated with coronary disease [1,2] and is characterized by an increased LDL particle number due to increased secretion of B100 lipoproteins by the liver [3]. The first feature of hyperapoB to be recognized was the elevated LDL particle number, many of which are smaller and denser than normal [4]. In reality, though, the metabolism of all the lipoprotein classes is demonstrably abnormal.At the onset, however, it must be appreciated that hyperapoB is a phenotype, not a genotype, and there are multiple causes which produce increased hepatic secretion of B100 lipoprotein particles. The focus in this review, however, will be to outline how a reduced rate of fatty acid trapping by adipocytes can produce the pleiotropic features which characterize hyperapoB. At the end of this line of reasoning lies the conclusion that faults in fatty acid metabolism, not errors in the LDL pathway, are the commonest causes for the atherogenic dyslipoproteinaemias seen clinically.The features of hyperapoB to be explicated are: 1) increased hepatic VLDL secretion; 2) increased LDL particle number; 3) smaller denser LDL particles; 4) reduced HDL cholesterol levels; 4) postprandial hyperlipaemia with accumulation of triglyceride-rich remnants; 5) elevated plasma non-esterified fatty acid levels (NEFA); and 6) insulin resistance. Regulation of the rate of fatty acid storage by adipocytesThe normal sequence involved in the uptake by adipocytes of fatty acids released from chylomicrons can be summarized as follows: chylomicrons attach to endothelial cells and the triglyceride within them is rapidly hydrolysed by lipoprotein lipase (LPL) [5]. The rate at which chylomicron triglyceride hydrolysis proceeds is determined by the number of LPL molecules involved and by the rate at which the NEFA which are generated are removed from the capillary microenvironment.The NEFA which are liberated from the chylomicrons can enter the adipocyte to be trapped within it as triglyceride. Alternatively, they may bind to albumin, leave the capillary, and enter the general circulation. The proportion of NEFA released from chylomicrons which enter adipocytes is necessarily the reciprocal of the proportion which are not trapped by adipocytes and which then leave the microenvironment. Under normal circumstance, the proportions are about equal [6]. The proportion of NEFA which are trapped by adipocytes is determined by their rate of triglyceride synthesis, the major determinant of which is the acylation stimulating protein (ASP) pathway [7].ASP is the product of the ASP pathway and, as just noted, is the major determinant of the rate of triglyceride synthesis within adipocytes. The major features of the pathway are described elsewhere [8]. In brief, human adipocytes synthesize and secrete the three proteins of the alternate complement pathway which interact to form a 77 amino terminal fragment of C3, the terminal arginine of which is removed by carboxypeptidases to produce ASP. ASP then interacts specifically with a ...

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Substrate delivery as a determinant of hepatic apoB secretion.

Cited by 187 publications

References 91 publications

Different patterns of brisk walking are equally effective in decreasing postprandial lipaemia

Different patterns of brisk walking are equally effective in decreasing postprandial lipaemia

Role of insulin in hepatic fatty acid partitioning: emerging concepts

The pathogenetic role of impaired fatty acid trapping by adipocytes in generating the pleiotropic features of hyperapoB

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