Expression of hormone-sensitive lipase and its regulation by adrenaline in skeletal muscle

Langfort, Józef; Ploug, Thorkil; Ihlemann, Jacob; Saldo, Michele; Holm, Cecilia; Galbo, H.

doi:10.1042/bj3400459

Cited by 124 publications

(181 citation statements)

References 36 publications

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“…Accordingly, muscles with dominating type 1 fibres are more oxidative and show greater hormone-sensitive lipase activity than type 2 fibre containing glycolytic muscles [35]. We also demonstrated in this study higher basal lipolysis rates in m. gastrocnemius than in m. vastus lateralis.…”

Section: Discussionsupporting

confidence: 79%

Major differences in noradrenaline action on lipolysis and blood flow rates in skeletal muscle and adipose tissue in vivo

et al. 2005

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Aims/hypothesis: The regulation of skeletal muscle lipolysis is not fully understood. In the present study, the effects of systemic and local noradrenaline administration on lipolysis and blood flow rates in skeletal muscle and adipose tissue were studied in vivo. Methods: First, circulating noradrenaline levels were raised tenfold by a continuous i.v. infusion (n=12). Glycerol levels (an index of lipolysis) were measured in m. gastrocnemius and in abdominal adipose tissue using microdialysis. -10 −6 mol/l) (n=10). Local blood flow was monitored with the ethanol perfusion technique. Results: With regard to systemic noradrenergic stimulation, no change in fractional release of glycerol (difference between tissue and arterial glycerol) was seen in skeletal muscle. In adipose tissue it transiently increased twofold (p<0.0001), and the rate of appearance of glycerol in plasma showed the same kinetic pattern. Blood flow was reduced by 40% in skeletal muscle (p<0.005) and increased by 50% in adipose tissue (p<0.05). After noradrenaline stimulation in situ, a discrete elevation of skeletal muscle glycerol was registered only at the highest concentration of noradrenaline (10 −6 mol/l) (p<0.05). Adipose tissue glycerol doubled already at the lowest concentration (10 −8 mol/l) (p<0.05). In skeletal muscle a decrease in blood flow was seen at the highest noradrenaline concentrations (p<0.05). Conclusions/interpretation: Lipolysis and blood flow rates are regulated differently in adipose tissue and skeletal muscle. Adipose tissue displays a high, but transient (tachyphylaxia) sensitivity to noradrenaline, leading to stimulation of both lipolysis and blood flow rates. In skeletal muscle, physiological concentrations of noradrenaline decrease blood flow but have no stimulatory effect on lipolysis rates.

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Section: Discussionsupporting

confidence: 79%

Major differences in noradrenaline action on lipolysis and blood flow rates in skeletal muscle and adipose tissue in vivo

et al. 2005

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“…Still, a HFD substantially increased IMCL utilization in type IIa fibers. In this regard, it is reasonable to speculate that a HFD, probably by virtue of higher IMCL content, stimulated contraction-induced HSL activity in the active fraction of type IIa motor units while possibly promoting adrenalineinduced lipolysis in inactive type IIa fibers (45,67). By analogy, stimulation of glycogen phosphorylase by adrenaline (53) also can explain net glycogenolysis in inactive muscle fibers during exercise (2).…”

Section: Discussionmentioning

confidence: 99%

High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise

Proeyen

Szlufcik

Nielens

et al. 2011

Journal of Applied Physiology

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Van Proeyen K, Szlufcik K, Nielens H, Deldicque L, Van Dyck R, Ramaekers M, Hespel P. High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise. J Appl Physiol 111: 108 -116, 2011. First published May 5, 2011 doi:10.1152/japplphysiol.01459.2010In this study, we compared the effects of endurance training in the fasted state (F) vs. the fed state [ample carbohydrate intake (CHO)] on exercise-induced intramyocellular lipid (IMCL) and glycogen utilization during a 6-wk period of a hypercaloric (ϳϩ30% kcal/day) fat-rich diet (HFD; 50% of kcal). Healthy male volunteers (18 -25 yrs) received a HFD in conjunction with endurance training (four times, 60 -90 min/wk) either in F (n ϭ 10) or with CHO before and during exercise sessions (n ϭ 10). The control group (n ϭ 7) received a HFD without training and increased body weight by ϳ3 kg (P Ͻ 0.001). Before and after a HFD, the subjects performed a 2-h constant-load bicycle exercise test in F at ϳ70% maximal oxygen uptake rate. A HFD, both in the absence (F) or presence (CHO) of training, elevated basal IMCL content by ϳ50% in type I and by ϳ75% in type IIa fibers (P Ͻ 0.05). Independent of training in F or CHO, a HFD, as such, stimulated exercise-induced net IMCL breakdown by approximately twofold in type I and by approximately fourfold in type IIa fibers. Furthermore, exercise-induced net muscle glycogen breakdown was not significantly affected by a HFD. It is concluded that a HFD stimulates net IMCL degradation by increasing basal IMCL content during exercise in type I and especially IIa fibers. Furthermore, a hypercaloric HFD provides adequate amounts of carbohydrates to maintain high muscle glycogen content during training and does not impair exercise-induced muscle glycogen breakdown. skeletal muscle; fasted exercise; fat-rich feeding; energy substrate metabolism; muscle lipids IT IS WELL ESTABLISHED THAT dietary factors play an important role in modulating the acute and chronic metabolic responses to endurance exercise (30). In this regard, increased preexercise dietary fat supply stimulates energy provision via fat oxidation during exercise (8,33). By analogy, fatty acid infusion elevates the input of free fatty acids (FFAs) in the energy substrate mix fueling muscle contractions (22, 48a, 49). Furthermore, chronic exposure to a high-fat diet (HFD) also enhances the use of FFAs in endurance exercise (8,9,25,29,(32)(33)(34)58). This is, at least partly, due to upregulation of rate-limiting steps in fat metabolic pathways. Thus FFA oxidation can be stimulated with appropriate chronic exercise and/or nutrition (e.g., HFD), which upregulates pivotal steps in FFA catabolism such as fatty acid translocase (FAT)/CD36 (4, 9), ␤-hydroxyacyl CoA dehydrogenase (␤-HAD) (9, 31), and hormone-sensitive lipase (HSL) (58). However, it is still unclear whether these adaptations are specifically due to the increased FFA supply per se or result from decreased glucose availability. Omission of glucose ingestion during exercise a...

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“…This finding argues for a functional role of HSL in the mobilization of skeletal muscle lipid stores, specifically in the catabolism of DG. It has been proposed previously (15,53) that HSL might participate in the breakdown of lipid droplets that are present in the cytoplasm of skeletal myocytes. However, the main energy supply for skeletal muscle is provided by the glycolytic degradation of glucose.…”

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

544

532

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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...

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Expression of hormone-sensitive lipase and its regulation by adrenaline in skeletal muscle

Cited by 124 publications

References 36 publications

Major differences in noradrenaline action on lipolysis and blood flow rates in skeletal muscle and adipose tissue in vivo

Major differences in noradrenaline action on lipolysis and blood flow rates in skeletal muscle and adipose tissue in vivo

High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise

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

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