Free fatty acids increase hepatic glycogen content in obese males

Allick, Gideon; Sprangers, F.; Weverling, Gerrit-Jan; Ackermans, M. T.; Meijer, A.J.; Romijn, Johannes A.; Endert, E.; Bisschop, Peter H.; Sauerwein, Hans P.

doi:10.1016/j.metabol.2004.01.012

Cited by 12 publications

(13 citation statements)

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“…It has been shown that anti-lipolytic Aci may decrease insulin and increase blood glucose concentrations [51]. Thus, GH and Aci administration during exercise promote glucose production, and increased plasma blood glucose may also stimulate leptin secretion [50].…”

Section: Discussionmentioning

confidence: 99%

A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study

et al. 2011

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BackgroundNeuropeptide Y (NPY) is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue (AT). Acipimox (Aci) inhibits lipolysis in AT and reduces plasma glycerol and free fatty acid (FFA) levels. Exercise and Aci are enhancers of growth hormone (GH) and NPY secretion and exercise may alter leptin levels. We expect to find abnormal neuropeptidergic response in plasma and AT in patients with bulimia nervosa (BN). We hypothesize that Aci influences these peptides via a FFA-independent mechanism and that Aci inhibits lipolysis through a cyclic adenosine monophosphate (cAMP)-dependent pathway. Dysregulations of the AT-brain axis peptides might be involved in binge eating as is the case in BN.MethodsThe objective of this study was to determine the responses of plasma NPY, GH, leptin, FFA and glycerol levels to exercise in BN patients and healthy women (C) given the anti-lipolytic drug Aci or placebo. The secondary objective of this study was to compare the responses of extracellular glycerol levels and plasma glycerol levels to exercise alone or together with Aci administration in BN patients and C women. Extracellular glycerol was measured in vivo in subcutaneous (sc) abdominal AT using microdialysis. Eight BN and eight C women were recruited for this single-blind, randomized study. Aci or placebo was given 1 hour before the exercise (45 min, 2 W/kg of lean body mass [LBM]). NPY, GH, leptin, FFA, glycerol plasma and AT glycerol levels were measured using commercial kits.ResultsThe primary outcome of this study was that the exercise with Aci administration resulted in plasma NPY and GH increase (after a 45-minute exercise) and leptin (after a 90-minute post-exercise recovering phase) increased more in BN patients. The secondary outcomes of this study were that the exercise with Aci administration induced a higher decrease of extracellular glycerol in BN patients compared to the C group, while the exercise induced a higher increase of glycerol concentrations in sc abdominal AT of BN patients. Plasma glycerol levels decreased more in BN patients and plasma FFA levels were depressed in both groups after the exercise with Aci administration. The exercise induced similar increases in plasma NPY, GH, FFA and glycerol levels, and a similar decrease in the plasma leptin level in both groups.ConclusionsWe confirm the results of a single-blind, randomized, microdialysis study, i.e. that the Aci-induced elevation in plasma NPY and GH levels during the exercise is higher in BN patients and that Aci increased plasma leptin levels in the post-exercise recovering phase (90-minute) more in BN patients. The post-exercise rise (45-minute) in AT glycerol is much more attenuated by acute Aci treatment in BN patients. Simultaneously, we found facilitated turnover of plasma glycerol after the exercise together with Aci administration in BN. Our results support the hypotheses that Aci exerts an effect on the FFA-independent and cAMP-dependent mechanism.Trial Re...

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Section: Discussionmentioning

confidence: 99%

A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study

et al. 2011

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“…Reduced (22,25), unchanged (5), and increased (20) rates of glycogenolysis all have been reported. The associated metabolic features of diabetes may also play a role in glycogen metabolism because elevated fatty acids may inhibit glycogen mobilization (26). These discrepancies may be attributable to differences in methods for assessing glycogenolysis and gluconeogenesis, or to the study of patients at different stages of disease.…”

Section: Discussionmentioning

confidence: 99%

Role of Excess Glycogenolysis in Fasting Hyperglycemia Among Pre-Diabetic and Diabetic Zucker (fa/fa) Rats

et al. 2007

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Sources of plasma glucose and glucose turnover were investigated in 8-week-old (pre-diabetic) and 13-week-old (diabetic) Zucker (fa/fa) rats after a 24-h fast. Intraperitoneal 2 H 2 O was administered and [3,4-13 C 2 ]glucose and [U-13 C 3 ]propionate were infused into conscious active rats. 13 C nuclear magnetic resonance analysis of monoacetone glucose derived from blood glucose indicated that glucose production was increased significantly in 8-and 13-weekold fa/fa rats compared with age-matched Zucker (؉/؉) rats, and hepatic glycogen was dramatically higher among fa/fa animals regardless of age. Glycogenolysis, essentially 0 in ؉/؉ rats after a 24-h fast, was significant in fa/fa rats (11 ؎ 6 and 17 ؎ 7% of glucose production in 8-and 13-week-old rats, respectively), even after a 24-h fast. Tricarboxylic acid (TCA) cycle flux and efflux of carbon skeletons from the cycle (cataplerosis) were both significantly higher in fa/fa rats compared with controls, but net gluconeogenesis from the TCA cycle was not higher because products leaving the cycle were returned to the cycle via a pyruvate cycling pathway. Thus, pyruvate cycling flux increased in proportion to TCA cycle flux, leaving net gluconeogenesis unchanged in fa/fa animals compared with control animals. The distribution of 2 H in skeletal muscle glycogen suggested that at least a fraction of glucose molecules entering glycogen pass through phosphomannose isomerase. Diabetes 56:777-785, 2007

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“…*P Ͻ 0.005; **P Ͻ 0.001 for pairwise comparison between groups (effect of protocol). Because of the use of [2][3][4][5][6][7][8][9][10][11][12][13] C]glycerol at a rate of ϳ4.5 mol⅐kg Ϫ1 ⅐min…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, very preterm infants routinely receive parenteral nutrition (including gradually increasing amounts of lipids) because enteral nutrition is not tolerated in sufficient amounts. Intravenous lipid emulsions contain FFA and could, therefore, play a role in the pathophysiology of hyperglycemia in preterm infants, a mechanism comparable with those described in adults with diabetes (11).In healthy postabsorptive adults, FFA stimulate gluconeogenesis with a concomitant decrease in glycogenolysis, thereby maintaining the total glucose production at a constant rate (3,10, 13,16,36,46). In preterm infants, only three studies (12,48,55) have explored the effect of oral or intravenous lipid administration on glucose production in the first postnatal week, showing contradictory results.…”

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confidence: 91%

“…Finally, FFA elevation can also directly affect gene expression and protein levels of the gluconeogenic enzymes pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase (5, 6, 33). As discussed above, infusion of different lipids had variable effects on glycogenolysis (3,10,13,16,36,46). The mechanisms by which FFA influence glycogenolysis in healthy adults are not completely elucidated and could involve hepatic autoregulation and hormonal changes (9,10,16,30,42).…”

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confidence: 99%

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Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile

Kempen¹,

Crabben²,

Ackermans³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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-In preterm infants, both hypo-and hyperglycemia are a frequent problem. Intravenous lipids can affect glucose metabolism by stimulation of gluconeogenesis by providing glycerol, which is a gluconeogenic precursor, and/or free fatty acids (FFA), which are stimulants of the rate of gluconeogenesis. In 25 preterm infants, glucose production and gluconeogenesis were measured using stable isotope techniques during a 6-h infusion of glucose only, glucose plus glycerol, or glucose plus an intravenous lipid emulsion. Two lipid emulsions differing in FFA composition were used: Intralipid (ϳ60% polyunsaturated FFA) and Clinoleic (ϳ60% monounsaturated FFA). The rate of glucose infusion was 22 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 in all groups. During the study infusion, the FFA concentrations were higher in both lipid groups vs. the glycerol group (P Ͻ 0.001). Compared with baseline, the glucose production rate increased in the Intralipid group, whereas it decreased in the other groups (P ϭ 0.002) due to a significant increase in gluconeogenesis in the Intralipid group (P ϭ 0.016). The plasma glucose concentration was significantly higher during Intralipid infusion vs. the other groups (P ϭ 0.046). Our conclusion was that Intralipid enhanced glucose production by increasing gluconeogenesis in preterm infants. This can be ascribed to the stimulatory effect of FFA in addition to any effect of glycerol alone. The lack of stimulation of gluconeogenesis in the Clinoleic vs. the Intralipid group suggests that different classes of fatty acids exert different effects on glucose kinetics in preterm infants.glycerol; fatty acids unsaturated; stable isotopes; mass isotopomer distribution analysis IN PRETERM INFANTS, disturbances in glucose metabolism are a frequent problem. Both hypo-and hyperglycemia can occur (20). Hypoglycemia occurs mostly in the first days after birth. Despite routine intravenous glucose supply, the incidence of hypoglycemia is still ϳ20% in our Neonatal Intensive Care Unit, a referral unit for infants Ͻ32 wk gestational age. Besides hypoglycemia, hyperglycemia is a mounting phenomenon in neonatal medicine, especially in sick and/or low-birth-weight infants.Free fatty acids (FFA) could play a role in the pathophysiology of both hypo-and hyperglycemia, because they are well-known stimulants of the rate of gluconeogenesis (11).Because plasma FFA concentrations in preterm infants are much lower than in adults (18,19,49), the lack of FFA could be involved in restricted capacity for gluconeogenesis, predisposing these infants for hypoglycemia. On the other hand, very preterm infants routinely receive parenteral nutrition (including gradually increasing amounts of lipids) because enteral nutrition is not tolerated in sufficient amounts. Intravenous lipid emulsions contain FFA and could, therefore, play a role in the pathophysiology of hyperglycemia in preterm infants, a mechanism comparable with those described in adults with diabetes (11).In healthy postabsorptive adults, FFA stimulate gluconeogenesis with a concomitant decrease in...

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Free fatty acids increase hepatic glycogen content in obese males

Cited by 12 publications

References 20 publications

A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study

A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study

Role of Excess Glycogenolysis in Fasting Hyperglycemia Among Pre-Diabetic and Diabetic Zucker (fa/fa) Rats

Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile

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