Cellular aspects of fuel mobilization and selection in white adipocytes

Lafontan, Max; Langin, Dominique

doi:10.1079/pns19950037

Cited by 14 publications

(13 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, it is conceivable that other DG hydrolases that are differently expressed in various tissues are responsible for the variation of the FFA/DG ratio among tissues. The instrumental function of HSL as a DG hydrolase is consistent with earlier in vitro studies demonstrating that HSL can catalyze the hydrolysis of DG at a much higher rate than TG (37,56,57) and that DG lipase activity in mouse and rat adipose tissue can be inhibited efficiently by a specific HSL antibody (3,58). In normal cells the DG concentration is very low, and DG degradation is not rate-limiting during hormonally stimulated lipolysis (59).…”

Section: Discussionsupporting

confidence: 71%

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

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

Section: Discussionsupporting

confidence: 71%

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

View full text Add to dashboard Cite

show abstract

“…Short-term changes in the activity of HSL appear to be brought about mainly by changes in its phosphorylation state (for detailed review, see Lafontan & Langin, 1995). The factors which lead to its activation during an overnight fast are not clear.…”

Section: Fat Mobilization In the Post-absorptive Statementioning

confidence: 99%

Fuel selection in white adipose tissue

Frayn¹,

Humphreys²

1995

Proc. Nutr. Soc.

View full text Add to dashboard Cite

Selection de substrats Cnergetiques dans le tissu adipeux blanc R E S U M ELavoisier a conclu que 'la respiration est donc une combustion'. Si ce concept est parfaitement valable pour un animal entier, il ne peut s'appliquer totalement au niveau du tissu. Le tissu adipeux blanc a un taux de consommation d'O2 trbs faible, mais ceci n'implique pas que son activitC mCtabolique est faible. En fait, c'est un tissu hautement spCcialisC qui s'est dtveloppC pour rCguler le flux de grandes quantitCs de substrats lipidiques, tout en consommant lui-mCme fort peu d'knergie. Les faibles besoins CnergCtiques du tissu adipeux blanc semblent Ctre largement satisfaits par l'utilisation du glucose, en partie en anaCrobie, et en partie en aCrobie. L'absorption du glucose se fait par l'intermkdiaire du GLUT-4, le transporteur du glucose rCgulC par l'insuline, avec un composant 'basal' plus petit par l'intermddiaire du GLUT-1. L'absorption de glucose est sensible B l'insuline in v i m , mais peut 1'Ctre moins in vivo, peut-&re parce qu'il est dCjB stimulC presque au maximum B des concentrations d'insuline physiologiques. I1 est possible Cgalement que le tissu adipeux blanc oxyde les acides aminCs B chaine ramifiCe. D'autres substrats CnergCtiques hydrosolubles comme les corps cCtoniques et l'adtate sont extraits du sang par le tissu adipeux blanc, bien qu'on ignore ce qu'ils deviennent. Le tissu adipeux blanc est l'ultime rCservoir d'Cnergie chimique dans le corps. En tant que tel, ce tissu doit rCguler le stockage net ou la perte de triacylglycCrol (TAG) pour rCpondre quantitativement au dCsCquilibre intCgrC entre l'absorption et la dCpense d'Cnergie (du corps tout entier) sur des pkriodes qui dkpassent quelques jours. On connait mieux maintenant les caractCristiques subtiles de la rCgulation mktabolique dans le tissu adipeux blanc par lesquelles ceci se produit. Le tissu adipeux blanc rCgule le flux des substrats lipidiques essentiellement en modulant I'activitC de deux enzymes, la lipase hormono-sensible (EC 3.1.1.3; LHS), et la lipase 1ipoprotCinique (EC 3.1.1.34; LLP). Le processus d'estkrification des acides gras est Cgalement rCgulC bien qu'on ne soit pas certain du site exact de cette rkgulation. La LHS et la LLP sont rCgulCes de mani6re rkciproque. Dans les situations aigues d'alimentation et de jeQne entre les repas, cette rCgulation semble Ctre effectuke essentiellement par des modifications dans la concentration d'insuline plasmatique. (Dans des situations 'de stress' telles que l'exercice physique, c'est le systbme sympatho-adrhalique qui joue le r81e principal dans la mobilisation des graisses.) Aprbs le jeQne de la nuit, la LHS est active alors que la LLP Pest moins. Les acides gras libCrCs par l'action de la LHS sur le TAG intra-cellulaire

show abstract

“…WAT has an abundant vascular and nervous supply and is located mainly in the subcutaneous region and around the viscera. The stored triacylglycerols in WAT provide long-term fuel reserve for the organism as a whole (2). An increase in the levels of nutrients and insulin stimulates triacylglycerol synthesis in liver and storage in WAT (2).…”

mentioning

confidence: 99%

“…The stored triacylglycerols in WAT provide long-term fuel reserve for the organism as a whole (2). An increase in the levels of nutrients and insulin stimulates triacylglycerol synthesis in liver and storage in WAT (2). Conversely, insulin falls during fasting, and epinephrine, glucocorticoids, and growth hormone increase, resulting in lipolysis and release of fatty acids that undergo partial oxidation in muscle and liver (2).…”

mentioning

confidence: 99%

“…An increase in the levels of nutrients and insulin stimulates triacylglycerol synthesis in liver and storage in WAT (2). Conversely, insulin falls during fasting, and epinephrine, glucocorticoids, and growth hormone increase, resulting in lipolysis and release of fatty acids that undergo partial oxidation in muscle and liver (2). Ketones generated from this process serve as alternate fuels for use by the brain and peripheral organs.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Brain Adipocytokine Action and Metabolic Regulation

et al. 2006

View full text Add to dashboard Cite

Adipose tissue secretes factors that control various physiological systems. The fall in leptin during fasting mediates hyperphagia and suppresses thermogenesis, thyroid and reproductive hormones, and immune system. On the other hand, rising leptin levels in the fed state stimulate fatty acid oxidation, decrease appetite, and limit weight gain. These divergent effects of leptin occur through neuronal circuits in the hypothalamus and other brain areas. Leptin also regulates the activities of enzymes involved in lipid metabolism, e.g., AMP-activated protein kinase and stearoyl-CoA desaturase-1, and also interacts with insulin signaling in the brain. Adiponectin enhances fatty acid oxidation and insulin sensitivity, in part by stimulating AMP-activated protein kinase phosphorylation and activity in liver and muscle. Moreover, adiponectin decreases body fat by increasing energy expenditure and lipid catabolism. These effects involve peripheral and possibly central mechanisms. Adipose tissue mediates interconversion of steroid hormones and secretes proinflammatory cytokines, vasoactive peptides, and coagulation and complement proteins. Understanding the actions of these "adipocytokines" will provide insight into the pathogenesis and treatment of obesity and related diseases. Diabetes 55 (Suppl. 2): S145-S154, 2006 ADIPOSE TISSUE

show abstract

Cellular aspects of fuel mobilization and selection in white adipocytes

Cited by 14 publications

References 76 publications

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

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

Fuel selection in white adipose tissue

Brain Adipocytokine Action and Metabolic Regulation

Contact Info

Product

Resources

About