Adipocyte G-proteins and adenylate cyclase. Effects of adrenalectomy

Ros, Manuel; Northup, John K.; Malbon, Craig C.

doi:10.1042/bj2570737

Cited by 40 publications

(37 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although infusion of fairly high concentrations of GCs increases systemic free fatty acids and glycerol within several hours in overnight-fasted humans ( venous-arterial differences for FAs across abdominal subcutaneous adipose tissue (35). Results from long-term (days to weeks) infusion of GCs (3,(42)(43)(44) are complicated by compensatory hyperinsulinemia, which may chronically promote higher FA flux via induction of insulin resistance and activation of the sympathetic nervous system, and the well-known ability of GCs to increase expression of ␤-adrenergic receptors and responsiveness to ␤-adrenergic agonists (16,17,23,32). Consistent with this possibility, we found that DEX increased the magnitude (fold stimulation) of the ␤-adrenergic activation of lipolysis.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes

Lee

Fried

2012

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

High concentrations of TNF within obese adipose tissue increase basal lipolysis and antagonize insulin signaling. Adipocytes of the obese are also exposed to elevated levels of glucocorticoids (GCs), which antagonize TNF actions in many cell types. We tested the hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and that GCs antagonize this effect in differentiated human adipocytes. Lipolysis and expression levels of lipolytic proteins were measured after treating adipocytes with TNF, dexamethasone (DEX), or DEX + TNF for up to 48 h. TNF not only increased basal lipolysis, it caused resistance to the antilipolytic effects of insulin in human adipocytes. DEX alone did not significantly affect lipolysis. Cotreatment with DEX blocked TNF induction of basal lipolysis and insulin resistance by antagonizing TNF stimulation of PKA-mediated phosphorylation of hormone-sensitive lipase (HSL) at Ser⁵⁶³ and Ser⁶⁶⁰ and perilipin. TNF did not affect perilipin, HSL, or phosphodiesterase-3B mass but paradoxically suppressed adipose tissue triglyceride lipase expression, and this effect was blocked by DEX. The extent to which GCs can restrain the lipolytic actions of TNF may both diminish the potentially deleterious effects of excess lipolysis and contribute to fat accumulation in obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes

Lee

Fried

2012

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…The immune complexes were made visible by staining with a second antibody (goat anti-rabbit IgG) coupled to calf alkaline phosphatase (44).…”

Section: Methodsmentioning

confidence: 99%

Activation of Rat Frizzled-1 Promotes Wnt Signaling and Differentiation of Mouse F9 Teratocarcinoma Cells via Pathways That Require Gαq and Gαo Function

Liu¹,

Liu²,

Wang³

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

The frizzled gene family of putative Wnt receptors encodes proteins that have a seven transmembranespanning motif characteristic of G-protein-linked receptors, although no loss-of-function studies have demonstrated a requirement for G-proteins for Wnt signaling by the gene product of frizzled-1. Medium conditioned by mouse F9 teratocarcinoma stem cells stably transfected to express either Xenopus Wnt-5a or Wnt-8 was used to test primitive endoderm formation of F9 stem cells. F9 stem cells expressing the rat Frizzled-1 receptors demonstrated endoderm formation in response to conditioned medium containing Wnt-8 but not to medium containing Wnt-5a. Primitive endoderm formation stimulated by Wnt-8 acting on the rat Frizzled-1 receptor was blocked by treatment with pertussis toxin by depletion of either G␣ o or G␣ q via antisense oligodeoxynucleotides, as well as by inhibitors of protein kinase C (bisindoylmaleimide) and of mitogen-activated protein kinase kinase (PD98059). Our results demonstrate the requirement for G-protein subunits G␣ o (a pertussis toxin substrate) and G␣ q for signaling by Frizzled-1, and an obligate role for the protein kinase C (likely mediated through stimulation of G␣ q ) and mitogen-activated protein kinase network at the level of mitogen-activated protein kinase kinase.Wnts are a class of vertebrate genes encoding secreted signaling proteins, which appear to modulate diverse processes in developing vertebrate embryos and in some adult tissues (1-4). The actions of Wnts are thought to be mediated by the function of members of the frizzled gene family of prospective heptihelical receptors (5-10). In the absence of a Wnt signal, active glycogen-synthase kinase 3 (zeste white 3/shaggy in Drosophila) phosphorylates ␤-catenin at an amino-terminal site (11), targeting it for ubiquitination and degradation through a proteosome pathway that also involves axin and the product of the adenomatous polyposis coli gene (12-21). Signaling by Wnt-1 via Frizzled homologues activates the function of Dishevelled, which represses the activity of glycogen-synthase kinase-3 (3, 22), promoting elevation of intracellular ␤-catenin levels and accumulation of ␤-catenin in nuclei (11, 23). Nuclear ␤-catenin interacts with members of the lymphoid-enhancer factor/T-cell factor (LEF/TCF) classes of architectural high mobility group (HMG) box transcription factors (24 -27) to regulate expression of genes involved in vertebrate development (24, 28 -32).Some Wnts can work through a pathway distinct from the glycogen-synthase kinase 3-mediated one described above (2,(33)(34)(35), depending upon what receptors are present. Xwnt-5a, unlike Wnt-1 and Xwnt-8, does not induce a duplication of the axis in Xenopus when ectopically expressed, but instead causes morphogenetic defects (33, 34). Whereas Xwnt-1, -8, -8b, and -3a are functionally equivalent in axis induction assays, Xwnt5a, -4, and -11 are functionally equivalent in this second, distinct Wnt signaling activity (36,37). This classification of Wnt ligand resembles the cl...

show abstract

“…Glucocorticoids also increase p-adrenergic receptor number, but in contrast to growth hormone, decrease maximum adenylate cyclase activity Ros et al 1989). Adrenalectomy increases response to adenosine (Saggerson, 1980;De Mazancourt et al 1989).…”

Section: T H E Manipulation Of Adipositymentioning

confidence: 99%

Effects of diet on lipolysis and its regulation

Vernon

1992

Proc. Nutr. Soc.

View full text Add to dashboard Cite

The amount of lipid in a fat cell (adipocyte) is determined by the rate of lipolysis as well as the rate of lipid synthesis. Both processes occur simultaneously and continuously, their relative rates determining if there is net lipid loss or accretion. REGULATIONS OF LIPOLYSISAcute control. Hydrolysis of triacylglycerols is catalysed by hormone-sensitive lipase. The activity of this enzyme is enhanced by phosphorylation by cyclic-AMP-dependent kinase (A-kinase). Hormone-sensitive lipase, and hence lipolysis, is thus acutely stimulated by a variety of hormones (e.g. adrenaline, glucagon, adrenocorticotrophic hormone (ACTH)) and the neurohumoral transmitter, noradrenaline, which increase the adenylate cyclase-A-kinase signal transduction system. Each peptide hormone interacts with its own receptor in the plasma membrane while adrenaline and noradrenaline interact with the P-adrenergic receptor. These hormone-receptor interactions lead to dissociation and activation of the GTP-binding protein, G,, which in turn leads to activation of adenylate cyclase (also located in the plasma membrane) and the synthesis of cyclic-AMP (Fig. 1). Cyclic-AMP activates A-kinase which in turn phosphorylates and activates hormone-sensitive lipase. Signal transduction through this system is modulated by noradrenaline and adrenaline acting via a second receptor, the 1x2-adrenergic receptor, and by prostaglandins (El and E2) and adenosine, both produced within adipose tissue, and acting via their own receptors. These receptors are coupled to a second GTP-binding protein, Gi. Receptor activation leads to dissociation of Gi which inhibits adenylate cyclase (Fig. 1). Catecholamines can, thus, both stimulate and inhibit lipolysis, the net effect depending on the relative numbers of p-and cx2-adrenergic

show abstract

Adipocyte G-proteins and adenylate cyclase. Effects of adrenalectomy

Cited by 40 publications

References 40 publications

Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes

Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes

Activation of Rat Frizzled-1 Promotes Wnt Signaling and Differentiation of Mouse F9 Teratocarcinoma Cells via Pathways That Require Gαq and Gαo Function

Effects of diet on lipolysis and its regulation

Contact Info

Product

Resources

About