Lactate-induced stimulation of myocardial triacylglycerol turnover

Groot, M.J.M. de; Willemsen, P. H. M.; Coumans, Will A.; Bilsen, Marc van; Vusse, Ger J.

doi:10.1016/0005-2760(89)90330-5

Cited by 28 publications

(16 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three decades ago Randle and co-workers demonstrated in the isolated rat heart that both glucose uptake and oxidation are inhibited by high FFA concentrations (53 (55,56). The possibility of alternative fuels (FFA, lactate) substitution for glucose in the current study is supported by the inverse association in the multivariate analysis between heart glucose disposal and circulating FFA and lactate concentrations.…”

Section: Discussionsupporting

confidence: 60%

Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscle.

Nuutila¹,

Knuuti²,

Heinonen³

et al. 1994

J. Clin. Invest.

View full text Add to dashboard Cite

Physical training increases skeletal muscle insulin sensitivity. Since training also causes functional and structural changes in the myocardium, we compared glucose uptake rates in the heart and skeletal muscles of trained and untrained individuals. Seven male endurance athletes (VO2max 72±2 ml/kg/min) and seven sedentary subjects matched for characteristics other than VO2max (43±2 ml/kg/min) were studied. Whole body glucose uptake was determined with a 2-h euglycemic hyperinsulinemic clamp, and regional glucose uptake in femoral and arm muscles, and myocardium using "F-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose uptake in the athletes was increased by 68% in whole body (P < 0.0001), by 99% in the femoral muscles (P < 0.01), and by 62% in arm muscles (P = 0.06), but it was decreased by 33% in the heart muscle (P < 0.05) as compared with the sedentary subjects. The total glucose uptake rate in the heart was similar in the athletes and control subjects. Left ventricular mass in the athletes was 79% greater (P < 0.001) and the meridional wall stress smaller (P < 0.001 ) as estimated by echocardiography. VO2max correlated directly with left ventricular mass (r = 0.87, P < 0.001) and inversely with left ventricular wall stress (r = -0.86, P < 0.001). Myocardial glucose uptake correlated directly with the rate-pressure product (r = 0.75, P < 0.02) and inversely with left ventricular mass (r = -0.60, P < 0.05) or with the whole body glucose disposal (r = -0.68, P < 0.01). Thus, in athletes, (a) insulin-stimulated glucose uptake is enhanced in the whole body and skeletal muscles, (b) whereas myocardial glucose uptake per muscle mass is reduced possibly due to decreased wall stress and energy requirements or the use of alternative fuels, or both. (J. Clin. Invest. 1994Invest. . 2267Invest. -2274

show abstract

Section: Discussionsupporting

confidence: 60%

Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscle.

Nuutila¹,

Knuuti²,

Heinonen³

et al. 1994

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Accordingly, skeletal muscle TG stores were not altered in HSL-ko mice. In contrast to skeletal muscle, the metabolic requirements of cardiac muscle are met by an extremely high lipolytic turnover of myocardial TG (54). Cardiac muscle TG breakdown is under acute hormonal control, and the discovery of HSL in cardiomyocytes (2,55) suggests that HSL is responsible for the intracellular lipolysis of TG.…”

Section: Discussionmentioning

confidence: 99%

Hormone-sensitive Lipase Deficiency in Mice Causes Diglyceride Accumulation in Adipose Tissue, Muscle, and Testis

Haemmerle¹,

Zimmermann²,

Hayn³

et al. 2002

Journal of Biological Chemistry

542

532

View full text Add to dashboard Cite

Hormone-sensitive lipase (HSL) is expressed predominantly in white and brown adipose tissue where it is believed to play a crucial role in the lipolysis of stored triglycerides (TG), thereby providing the body with energy substrate in the form of free fatty acids (FFA). From in vitro assays, HSL is known to hydrolyze TG, diglycerides (DG), cholesteryl esters, and retinyl esters. In the current study we have generated HSL knock-out mice and demonstrate three lines of evidence that HSL is instrumental in the catabolism of DG in vivo. First, HSL deficiency in mice causes the accumulation of DG in white adipose tissue, brown adipose tissue, skeletal muscle, cardiac muscle, and testis. Second, when tissue extracts were used in an in vitro lipase assay, a reduced FFA release and the accumulation of DG was observed in HSL knock-out mice which did not occur when tissue extracts from control mice were used. Third, in vitro lipolysis experiments with HSL-deficient fat pads demonstrated that the isoproterenol-stimulated release of FFA was decreased and DG accumulated intracellularly resulting in the essential absence of the isoproterenolstimulated glycerol formation typically observed in control fat pads. Additionally, the absence of HSL in white adipose tissue caused a shift of the fatty acid composition of the TG moiety toward increased long chain fatty acids implying a substrate specificity of the enzyme in vivo. From these in vivo results we conclude that HSL is the rate-limiting enzyme for the cellular catabolism of DG in adipose tissue and muscle. Hormone-sensitive lipase (HSL)1 is thought to be a key enzyme for the mobilization of triglycerides (TG) deposited in adipose tissue. Human HSL is composed of 775 amino acids that are encoded by a 2.9-kb mRNA transcribed from a single gene composed of 9 exons (1, 2). The mouse and the human genes are similar in size and share a high degree of sequence homology. A tissue-specific size variation has been observed in testis where an additional exon 13 kb upstream of exon 1 in adipose tissue gives rise to a 3.9-kb mRNA and a 1076-amino acid protein (3). The molecular basis of size variations in HSL mRNA in muscle, macrophages, and ovaries is unknown.HSL-mediated lipolysis is strictly controlled by hormones. The enzyme is activated by catecholamines and other lipolytic hormones upon phosphorylation by the cAMP-dependent protein kinase A and the lipotransin-mediated translocation of the enzyme from the cytoplasm to the lipid droplet (4 -6). Insulin, the major antilipolytic hormone, inhibits HSL through phosphodiesterase-3-dependent cAMP degradation and interference with the lipotransin-mediated enzyme translocation. Accordingly, mice with elevated protein kinase A activity exhibit increased lipolysis and a lean phenotype (7). Absence of perilipin in mice also resulted in leanness through constitutive activation of HSL (8). Conversely, mice that lack the insulin receptor substrate 2 become obese (9). These results imply that imbalances between lipid accumulation and fat mobilizati...

show abstract

“…Fat accumulation in cardiac cells can be prevented when hydrolysis of the endogenous triacylglycerol pool keeps pace with synthesis. In this respect recent findings of De Groot and colleagues [28] are worth mentioning. In isolated rat hearts, perfused in the presence of 11mM glucose plus 5 mM lactate the Table 1 in Drake et al [15].…”

Section: The Effect Of Lactate On Endogenous Esterified Lipid Storesmentioning

confidence: 93%

“…Among others, intracellular fatty acids may act as feed-back inhibitors of the hydrolytic activity [30,31]. Since increased glycerol release is associated with enhanced tissue fatty acid levels in lactate perfused hearts [28] it is highly unlikely that endogenous fatty acids inhibit intracellular lipases in vivo. It should be noted that the level of fatty acids needed to block lipase activity in vitro [31,32] is appreciably higher than the content measured in lactate perfused hearts [26,281. Increased triacylglycerol hydrolysis is most likely closely related to the rate of triacylglycerol synthesis.…”

Section: The Effect Of Lactate On Endogenous Esterified Lipid Storesmentioning

confidence: 99%

Interrelationship between lactate and cardiac fatty acid metabolism

Vusse¹,

Groot

1992

Mol Cell Biochem

Self Cite

View full text Add to dashboard Cite

This overview is presented, in the main, to summarize the following aspects of lactate and cardiac fatty acid metabolism: 1. The utilization of exogenous carbohydrates and fatty acids by the heart. 2. The competition between lactate and fatty acids in cardiac energy metabolism. 3. The effect of lactate on endogenous triacylglycerol homeostasis. 4. Lactate-induced impairment of functional recovery of the post-ischemic heart. 5. The effect of lactate on lipid metabolism in the ischemic and post-ischemic heart. 6. The consequences of hyperlactaemia for cardiac imaging.

show abstract

Lactate-induced stimulation of myocardial triacylglycerol turnover

Cited by 28 publications

References 21 publications

Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscle.

Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscle.

Hormone-sensitive Lipase Deficiency in Mice Causes Diglyceride Accumulation in Adipose Tissue, Muscle, and Testis

Interrelationship between lactate and cardiac fatty acid metabolism

Contact Info

Product

Resources

About