O.5 Intravenous lipid emulsions, removal mechanismsas compared to chylomicrons

Hultin, Magnus; Carneheim, C.; Rosengvist, K.; Olivecrona, T.

doi:10.1016/s0261-5614(95)80077-8

Cited by 57 publications

(84 citation statements)

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“…To achieve similar circulating FA concentrations in the two diet groups, it was necessary to infuse HFF with intralipid at twice the rate of CON. It is likely that this reflects an enhanced clearance of infused triglyceride without previous lipolysis, as it is known that a large fraction of triglyceride in artificial emulsions can be cleared without degradation (27).…”

Section: Resultsmentioning

confidence: 99%

Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats

Hegarty

Cooney²,

Kraegen³

et al. 2002

Diabetes

141

111

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In humans and animal models, increased lipid content of skeletal muscle is strongly associated with insulin resistance. However, it is unclear whether this accumulation is due to increased uptake or reduced utilization of fatty acids (FAs). We used 3 H-R-bromopalmitate tracer to assess the contribution of tissue-specific changes in FA uptake to the lipid accumulation observed in tissues of insulin-resistant, high fat-fed rats (HFF) compared with control rats (CON) fed a standard diet. To study FA metabolism under different metabolic states, tracer was infused under basal conditions, during hyperinsulinemic-euglycemic clamp (low FA availability) or during the infusion of intralipid and heparin (high FA availability). FA clearance was significantly increased in the red gastrocnemius muscle of HFF under conditions of low (HFF ‫؍‬ 10.4 ؎ 1.1; CON ‫؍‬ 7.4 ؎ 0.5 ml ⅐ min ؊1 ⅐ 100 g ؊1 ; P < 0.05), basal (HFF ‫؍‬ 8.3 ؎ 1.4; CON ‫؍‬ 4.5 ؎ 0.7 ml ⅐ min ؊1 ⅐ 100 g ؊1 ; P < 0.01), and high (HFF ‫؍‬ 7.0 ؎ 0.8; CON ‫؍‬ 4.3 ؎ 0.5 ml ⅐ min ؊1 ⅐ 100 g ؊1 ; P < 0.05) FA levels. This indicates an adaptation by muscle for more efficient uptake of lipid. Associated with the enhanced efficiency of FA uptake, we observed increases in CD36/FA translocase mRNA expression (P < 0.01) and acyl-CoA synthetase activity (P < 0.02) in the same muscle. FA clearance into white adipose tissue was also increased in HFF when circulating FA were elevated, but there was little effect of the high-fat diet on hepatic FA uptake. In conclusion, insulin resistance induced by feeding rats a high-fat diet is associated with tissue-specific adaptations that enhance utilization of increased dietary lipid but could also contribute to the accumulation of intramuscular lipid with a detrimental effect on insulin action.

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Section: Resultsmentioning

confidence: 99%

Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats

Hegarty

Cooney²,

Kraegen³

et al. 2002

Diabetes

141

111

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“…However, there is substantial evidence that TGRLs are not solely catabolised in the liver, but are taken up also by other tissues. In fact, chylomicron remnant uptake by the liver ranges, in various studies, from 80% down to 20% [47,48].…”

Section: Discussionmentioning

confidence: 99%

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

et al. 2005

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Aims/hypothesis: Elevated fasting and postprandial plasma levels of triglyceride-rich lipoproteins (TGRLs), i.e. VLDL/remnants and chylomicrons/remnants, are a characteristic feature of insulin resistance and are considered a consequence of this state. The aim of this study was to investigate whether intact TGRL particles are capable of inducing insulin resistance. Methods: We studied the effect of highly purified TGRLs on glycogen synthesis, glycogen synthase activity, glucose uptake, insulin signalling and intramyocellular lipid (IMCL) content using fully differentiated L6 skeletal muscle cells. Results: Incubation with TGRLs diminished insulin-stimulated glycogen synthesis, glycogen synthase activity, glucose uptake and insulin-stimulated phosphorylation of Akt and glycogen synthase kinase 3. Insulin-stimulated tyrosine phosphorylation of IRS-1, and IRS-1-and IRS-2-associated phosphatidylinositol 3-kinase (PI3K) activity were not impaired by TGRLs, suggesting that these steps were not involved in the lipoprotein-induced effects on glucose metabolism. The overall observed effects were time-and dose-dependent and paralleled IMCL accumulation. NEFA concentration in the incubation media did not increase in the presence of TGRLs indicating that the effects observed were solely due to intact lipoprotein particles. Moreover, co-incubation of TGRLs with orlistat, a potent active-site inhibitor of various lipases, did not alter TGRL-induced effects, whereas co-incubation with receptor-associated protein (RAP), which inhibits interaction of TGRL particles with members of the LDL receptor family, reversed the TGRL-induced effects on glycogen synthesis and insulin signalling. Conclusions/ interpretation: Our data suggest that the accumulation of TGRLs in the blood stream of insulin-resistant patients may not only be a consequence of insulin resistance but could also be a cause for it.

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“…1 There is evidence that Intralipid particles in the circulation rapidly acquire the apolipoproteins necessary for removal, 27,28 and it has been assumed that their clearance re¯ects that of chylomicron-TG (reviewed in Ref. 29), although the half-life in the circulation is greater than that of chylomicrons. 30 Our results, in contrast, suggest that removal is not mainly by LPL-mediated TG hydrolysis in peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

“…This view is borne out by recent observations on the metabolism of TG emulsions compared with chylomicrons in rats. 29 Our study involved a small number of subjects, and the lack of demonstration of signi®-cant extraction of plasma TG across the tissues almost certainly re¯ects a lack of precision to measure small arteriovenous differences against a high arterial`background', in other words, a type II statistical error. Nevertheless, the difference from previous studies with fat ingestion is clear.…”

Section: Discussionmentioning

confidence: 99%

Peripheral fat metabolism during infusion of an exogeneous triacylglycerol emulsion

Samra¹,

Giles²,

Summers³

et al. 1998

Int J Obes

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OBJECTIVE: To test the hypothesis that intravenous infusion of lipid would bring about changes in adipose tissue metabolism, which would tend to spare net fat mobilization, and to attempt to identify the mediators of such responses. DESIGN: The triacylglycerol (TG) emulsion, Intralipid, was infused and metablic changes in subcutaneous adipose tissue and forearm muscle were assessed by measurements of arterio-venous differences. SUBJECTS: Six normal male subjects aged 21 ± 37 y, with body mass index (BMI) 23.0 ± 25.9 kgam 2 . RESULTS: Plasma TG and non-esteri®ed fatty acid (NEFA) concentrations rose during infusion as expected. The rise in systemic plasma NEFA concentration occurred despite decreased NEFA release from adipose tissue. Intralipid infusion resulted in a suppression of intracellular lipolysis in adipose tissue, by mechanisms which are not clear. Plasma leptin concentrations, measured in a search for the regulator of lipolysis, showed consistent leptin release from adipose tissue which did not change signi®cantly with time. CONCLUSION: The suppression of intracellular lipolysis in adipose tissue during Intralipid infusion is a new observation and may re¯ect a novel mechanism for regulation of fat storage.

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O.5 Intravenous lipid emulsions, removal mechanismsas compared to chylomicrons

Cited by 57 publications

References 0 publications

Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats

Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

Peripheral fat metabolism during infusion of an exogeneous triacylglycerol emulsion

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