Regulation of adipose tissue lipolysis: effects of noradrenaline and insulin on phosphorylation of hormone‐sensitive lipase and on lipolysis in intact rat adipocytes

Nilsson, Nils Östen; Strålfors, Peter; Fredrikson, Gudrun; Belfrage, Per

doi:10.1016/0014-5793(80)80776-9

Cited by 114 publications

(62 citation statements)

References 13 publications

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“…This is consistent with the finding in [7] that cyclic GMP-dependent protein kinase phosphorylated the lipase to the same level at both sites without any additional effects on the activity. Taken together with previous findings [5,7] it also demonstrates that phosphorylation of the basal phosphorylation site is not a prerequisite for the phosphorylation of the regulatory site in vitro, a kind of sequential phosphorylation that has previously been reported to be necessary for, or strongly potentiate, the phosphorylation of several substrates by glycogen synthase kinase-3 [ 3,6], this indicates a rapid turnover of the phosphate at this site. The incorporation of phosphate into the respective sites of the lipase protein was somewhat lower in the present work, for unknown reasons.…”

Section: Discussionsupporting

confidence: 86%

“…The phosphate at this site turns over rapidley [3,6] and it appears to be highly phosphorylated in unstimulated adipocytes [3]. The function of this phosphorylation is not known.…”

Section: Sds-page Sds-polyacrylamide Gel Electrophoresismentioning

confidence: 99%

“…Addition of insulin to noradrenaline-stimulated fat cells causes a rapid net dephosphorylation of the regulatory phosphorylation site and inhibition of the lipolysis [4,6].…”

Section: Introductionmentioning

confidence: 99%

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Phosphorylation of the basal site of hormone‐sensitive lipase by glycogen synthase kinase‐4

Olsson¹,

Strålfors²,

Belfrage³

1986

FEBS Letters

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In rat adipocytes hormone-sensitive lipase is phosphorylated at two sites termed 'regulatory' and 'basal', in the former case by cyclic AMP-dependent protein kinase causing an activation of the lipase [( 1984) Proc. Natl. Acad. Sci. USA 8 1,33 17-33211. Here, the basal phosphorylation site was found to be phosphorylated by glycogen synthase kinase-4 without any effects on lipase activity, or on the extent of its activation subsequent to phosphorylation of the regulatory site. Glycogen synthase kinase3, casein kinase-I, and casein kinase-II did not phosphorylate the lipase. Phosphorylase kinase phosphorylated it to a very low extent at a third phosphorylation site not phosphorylated in the fat cell.

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Section: Discussionsupporting

confidence: 86%

“…The phosphate at this site turns over rapidley [3,6] and it appears to be highly phosphorylated in unstimulated adipocytes [3]. The function of this phosphorylation is not known.…”

Section: Sds-page Sds-polyacrylamide Gel Electrophoresismentioning

confidence: 99%

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Phosphorylation of the basal site of hormone‐sensitive lipase by glycogen synthase kinase‐4

Olsson¹,

Strålfors²,

Belfrage³

1986

FEBS Letters

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“…To date, dephosphorylation following exposure of cells to insulin has only been demonstrated directly in intact cells for fat cell triacylglycerol lipase (in the presence of noradrenaline) [ 127,128] and for fat cell pyruvate dehydrogenase [67]. We would like to suggest that the phosphorylation of the protein of subunit Mr 22,000 observed in insulin treated fat cells may turn out to play an important role in initiating the dephosphorylation of some cytoplasmic enzymes.…”

Section: Activation Of a Cyclic Nucleotide Independent Protein Kinasementioning

confidence: 95%

“…Detection of changes in the phosphorylation of a phosphoprotein (subunit Mr 85,000) which is most probably triacylglycerol lipase has been achieved by Belfrage and colleagues [127,128]. Due to the high specific activity of this enzyme, its concentration in fat cells is very low compared with many other phosphoproteins.…”

Section: Effects Of Insulin On Specific Protein Phosphorylation In Inmentioning

confidence: 99%

A partial view of the mechanism of insulin action

1981

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Insulin was discovered 60 years ago [1]; since then its structure has been determined by the pioneer work of Sanger [2] and by Hodgkin, Blundell and colleagues [3]. Moreover the principle effects of insulin on carbohydrate, fat and protein metabolism have been well recognised, at least ingeneral terms, for some 20 years [4][5][6][7], yet, we do not have a satisfactory description at the molecular level of how this hormone brings about its wide range of effects on target cells. This is certainly not due to any lack of attention to the problem by research workers. The literature on this subject is vast and, in the absence of any generally acceptable hypothesis, it also tends to be rather confused and certainly conflicting. Since it is quite unrealistic to survey the whole field, we make no apology for concentrating on certain aspects in this article.Insulin has both long and short term effects on the metabolism of its target cells. The long term effects involve changes in both general and specific protein synthesis and breakdown, while short term effects are those brought about solely through changes in the activity of pre-existing enzymes and membrane transporters. To a large extent, we will neglect all aspects of long term regulation including protein synthesis and amino acid metabolism. In fact, advances in these areas have been delayed by the lack of satisfactory preparations suitable for probing the mechanisms involved in the specific induction and repression of enzymes by insulin in vitro. This situation will probably change rapidly as a number of such preparations have been reported recently. Particularly promising are the 3T3-L1 preadipocyte cell line [8,9] and also the maintenance liver cell cultures from young rats in which glucokinase activity has been shown to be rapidly induced on exposure to insulin in the presence of glucose [10].In the rest of this review we will concentrate on those studies concerned with short term effects of insulin on carbohydrate and fat metabolism in the cells of liver, muscle and, particularly, adipose tissue. All these cells have specific insulin receptors on the outward face of the plasma membrane but we will not be considering the nature of these receptors nor their interaction with insulin nor the mechanisms which may govern the number of insulin receptors. These aspects have all been well covered in other recent reviews [11][12][13]. We shall address ourselves to the problem of the process or processes whereby alterations in the level of occupancy of the plasma membrane insulinreceptors lead to a wide range of intracellular changes. The assumption will be made that neither the whole insulin molecule nor part of it needsto enter the cells of its target tissue to bring about the effects of insulin. There seems little doubt that insulin bound to its receptor can be "internalized" into liver and probably other cells [14, 15], however, the process appears to be too slow to represent the means whereby insulin could bring about its short term effects. On the other hand, antibo...

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Rapid purification of detergent‐solubilized bovine hormone‐sensitive lipase by high performance hydrophobic interaction chromatography

Nilsson

Holm

Belfrage

1989

Biomedical Chromatography

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Hormone-sensitive lipase (HSL), the enzyme controlling the rate of adipose tissue lipolysis and also possibly involved in the regulation of steroidogenesis, has been purified from bovine omental adipose tissue. Partially detergent-solubilized, delipidated and purified HSL was obtained through step-elution at conventional DEAE ion-exchange chromatography, followed by concentration on hydroxylapatite. High performance hydrophobic interaction chromatography (HPHIC) on phenylsilica then resulted in an increase of HSL protein purity from 2% to more than 70%. Final purification of the enzyme to apparent homogeneity (greater than 95% protein purity), concentration and removal of most of the detergent was obtained by high performance cation exchange chromatography on Mono S. At least 0.5 mg of highly stable HSL was obtained from 5 kg of bovine omental fat within four working days. The purified lipase had a lower specific activity than previously reported for the corresponding rat enzyme but the preparations have proved very useful for enzyme structure studies and as an antigen.

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Regulation of adipose tissue lipolysis: effects of noradrenaline and insulin on phosphorylation of hormone‐sensitive lipase and on lipolysis in intact rat adipocytes

Cited by 114 publications

References 13 publications

Phosphorylation of the basal site of hormone‐sensitive lipase by glycogen synthase kinase‐4

Phosphorylation of the basal site of hormone‐sensitive lipase by glycogen synthase kinase‐4

A partial view of the mechanism of insulin action

Rapid purification of detergent‐solubilized bovine hormone‐sensitive lipase by high performance hydrophobic interaction chromatography

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