Effects of acipimox on the lipolysis rate in subcutaneous adipose tissue of obese subjects

Flechtner-Mors, Marion; Jenkinson, Christopher P.; Alt, Andreas; Adler, Guido; Ditschuneit, H.

doi:10.1002/dmrr.219

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…However, effects on oxidation rates may be limited, as ACI preferentially improves nonoxidative glucose disposal. Moreover, ACI stimulates skin blood flow (7); however, we do not suspect this to have a major impact on the tracer kinetics, as ACI has no effect on adipose tissue (9) or forearm blood flow (12,29). Second, our results cannot be extended to women or other patient groups.…”

Section: Discussionmentioning

confidence: 84%

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Kinetics and utilization of lipid sources during acute exercise and acipimox

Nellemann

Søndergaard

Jensen

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Nielsen S. Kinetics and utilization of lipid sources during acute exercise and acipimox. Am J Physiol Endocrinol Metab 307: E199 -E208, 2014. First published June 3, 2014 doi:10.1152/ajpendo.00043.2014.-Overweight is associated with abnormalities of lipid metabolism, many of which are reversed by exercise. We investigated the impact of experimental antilipolysis and acute exercise on lipid kinetics and oxidation from VLDL-TG, plasma FFA, and "residual lipids" in overweight men (n ϭ 8) using VLDL-TG and palmitate tracers in combination with muscle biopsies in a randomized, placebo-controlled design. Participants received placebo or acipimox on each study day (4 h of rest, 90 min of exercise at 50% V O2 max). Exercise suppressed VLDL-TG secretion significantly during placebo but not acipimox (placebo-rest: 64.2 Ϯ 9.4; placebo-exercise: 48.3 Ϯ 8.0; acipimox-rest: 55.2 Ϯ 13.4; acipimoxexercise: 52.0 Ϯ 10.9). Resting oxidation of VLDL-TG FA and FFA was significantly reduced during acipimox compared with placebo, whereas "residual lipid oxidation" increased significantly [VLDL-TG oxidation (placebo: 18 Ϯ 3 kcal/h; acipimox: 11 Ϯ 2 kcal/h), FFA oxidation (placebo: 14 Ϯ 2 kcal/h; acipimox: 4 Ϯ 0.5 kcal/h), and residual lipid oxidation (placebo: 3 Ϯ 5 kcal/h; acipimox: 14 Ϯ 5 kcal/h)]. Additionally, during exercise on both placebo and acipimox, oxidation of VLDL-TG and FFA increased, but the relative contribution to total lipid oxidation diminished, except for FFA, which remained unchanged during acipimox. Residual lipid oxidation increased significantly during exercise in both absolute and relative terms. Changes in selected cellular enzymes and proteins provided no explanations for kinetic changes. In conclusion, suppressed FFA availability blunts the effect of exercise on VLDL-TG secretion and modifies the contribution of lipid sources for oxidation. very low-density lipoprotein; exercise; antilipolysis; lipid oxidation OVERWEIGHT IS ASSOCIATED with proatherogenic abnormalities of lipid metabolism. The alterations reflect reduced insulin suppression of both hepatic very low-density lipoprotein triglyceride (VLDL-TG) secretion and adipose tissue lipolysis, leading to greater plasma triglycerides (TG) and free fatty acid (FFA) concentrations (30). Many of these abnormalities are reversed by physical exercise (21). During low-to moderateintensity exercise, fasting lipid oxidation accounts for ϳ50% of energy expenditure (EE) (25,33,46), and the major sources are plasma FFA, intramyocellular lipids (IML), and VLDL-TG fatty acids (FA). Plasma FFA oxidation (19), measured isotopically (15), increases rapidly during exercise. Conversely, measurements of VLDL-TG oxidation are methodologically challenging (24) and have been calculated mostly from regional A-V concentration differences (19); however, these differences cannot differentiate between tissue oxidation and storage, and IML oxidation has usually been calculated indirectly by subtracting plasma FFA oxidation from total lipid oxidation measured by indirect calorimetry (...

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Section: Discussionmentioning

confidence: 84%

“…Systemic palmitate flux and oxidation were measured using an isotope dilution technique, with a 1-h constant infusion of [9, (16,47). Data were insufficient in one participant.…”

Section: Methodsmentioning

confidence: 99%

Kinetics and utilization of lipid sources during acute exercise and acipimox

Nellemann

Søndergaard

Jensen

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…There is evidence that acipimox directly affects lipolysis in sc adipose tissue. Using microdialysis techniques, Flechtner-Mors et al (39) showed decreased glycerol outflow and therefore decreased lipolysis from sc fat depots among obese individuals after acipimox treatment. These data suggest a potential specific benefit of acipimox for HIV-infected patients in whom increased lipolytic rates in sc fat stores may contribute to increased FFA levels and to lipodystrophy.…”

Section: Discussionmentioning

confidence: 99%

Improved Triglycerides and Insulin Sensitivity with 3 Months of Acipimox in Human Immunodeficiency Virus-infected Patients with Hypertriglyceridemia

Hadigan

Liebau

Torriani

et al. 2006

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…The present study was designed to test this hypothesis using acipimox, a nicotinic acid derivative that suppresses both peripheral tissue lipolysis (7,23) and hepatic triglyceride release (20). To clarify more fully the relationship between fatty acid supply and EGP, nondiabetic subjects with a wide range of body weights were studied.…”

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confidence: 99%

Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production

Carey¹,

Gerrard²,

Cline³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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To test the hypothesis that intrahepatic availability of fatty acid could modify the rate of suppression of endogenous glucose production (EGP), acipimox or placebo was administered before and during a test meal. We used a modified isotopic methodology to measure EGP in 11 healthy subjects, and 1 H magnetic resonance spectroscopic measurement of hepatic triglyceride stores was also undertaken. Acipimox suppressed plasma free fatty acids markedly before the meal (0.05 Ϯ 0.01 mmol/l at Ϫ10 min, P ϭ 0) and throughout the postprandial period (0.03 Ϯ 0.01 mmol/l at 150 min). Mean peak plasma glucose was significantly lower after the meal on acipimox days (8.9 Ϯ 0.4 vs. 10.1 Ϯ 0.5 mmol/l, P Ͻ 0.01), as was mean peak serum insulin (653.1 Ϯ 99.9 vs. 909 Ϯ 118 pmol/l, P Ͻ 0.01). Fasting EGP was similar (11.15 Ϯ 0.58 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 placebo vs. 11.17 Ϯ 0.89 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 acipimox). The rate of suppression of EGP after the meal was almost identical on the 2 test days (4.36 Ϯ 1.52 vs. 3.69 Ϯ 1.21 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 at 40 min). There was a significant negative correlation between the acipimoxinduced decrease in peak plasma glucose and liver triglyceride content (r ϭ Ϫ0.827, P ϭ 0.002), suggesting that, when levels of liver fat were low, inhibition of lipolysis was able to affect glucose homeostasis. Acute pharmacological sequestration of fatty acids in triglyceride stores improves postprandial glucose homeostasis without effect on the immediate postprandial suppression of EGP. intrahepatic triglyceride; acipimox; 1 H magnetic resonance spectroscopy PLASMA GLUCOSE CONCENTRATION is determined by the interaction of two processes, the rate of release of glucose into the bloodstream and the rate of uptake of glucose by cells. In the fasted state, glucose is produced by the breakdown of glycogen stores or gluconeogenesis. In the postprandial state, absorption of glucose and other substrates from the intestine exceeds the body's energy requirements. Homeostasis is maintained by a rapid increase in insulin secretion that acutely suppresses hepatic glucose production and enhances glucose storage and oxidation.We (25) have previously shown, using novel isotopic methodology, that endogenous glucose production (EGP) was almost completely suppressed within 30 min postprandially in young normal subjects. However, a subsequent study on older, more obese normal subjects showed a slower, less complete postprandial suppression of EGP (21). Given that the major metabolic difference between our two groups of normal subjects was degree of obesity, we postulated that intrahepatic availability of fatty acid could modify the rate of suppression of EGP. Such an effect could explain the slower, incomplete suppression of EGP in subjects with type 2 diabetes. Conversely, if the fatty acid supply was curtailed, it would be expected that postprandial EGP suppression would be more rapid and more complete.The present study was designed to test this hypothesis using acipimox, a nicotinic acid derivative that suppresses both peripheral tissue li...

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Effects of acipimox on the lipolysis rate in subcutaneous adipose tissue of obese subjects

Abstract: In the present study basal glycerol outflow from adipose tissue was inhibited by acipimox. The anti-lipolytic action of the agent may diminish elevated plasma concentrations of free fatty acids in subjects with severe obesity.

Cited by 7 publications

References 23 publications

Kinetics and utilization of lipid sources during acute exercise and acipimox

Kinetics and utilization of lipid sources during acute exercise and acipimox

Improved Triglycerides and Insulin Sensitivity with 3 Months of Acipimox in Human Immunodeficiency Virus-infected Patients with Hypertriglyceridemia

Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production

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