Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats.

Cheng, Juei‐Tang; Liu, I-Min; Chi, Tzong‐Cherng; Shinozuka, Kazumasa; Lu, Feng-Hwa; Wu, Tong; Chang, Chai-Jan

doi:10.2337/diabetes.49.1.20

Cited by 42 publications

(28 citation statements)

References 14 publications

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“…Glucocorticoids exert a potent stimulatory effect on the Lep gene and leptin secretion (Kanu et al, 2003). Stimulation of the sympathetic nervous system and agents that increase intracellular cAMP levels inhibit leptin expression (Moreno-Aliaga et al, 2002), whereas studies exploring a possible role for insulin have yield contradictory results (Bradley & Cheatham, 1999;Cheng et al, 2000;Considine et al, 1997). In turn, leptin may exert negative autocrine effects on insulin action, (Kraus et al, 2002), and melatonin interacts with insulin, up-regulating insulin-stimulated leptin expression by means of signaling coactivation, regulating adipocyte biology, and modulating its metabolic and hormonal function (Alonso-Vale et al, 2005.…”

Section: Adipose Tissue Humoral and Molecular Regulators And The CLmentioning

confidence: 99%

Clock Genes and Clock-Controlled Genes in the Regulation of Metabolic Rhythms

Mazzoccoli

Pazienza

Vinciguerra

2012

Chronobiology International

148

109

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Daily rotation of the Earth on its axis and yearly revolution around the Sun impose to living organisms adaptation to nyctohemeral and seasonal periodicity. Terrestrial life forms have developed endogenous molecular circadian clocks to synchronize their behavioral, biological, and metabolic rhythms to environmental cues, with the aim to perform at their best over a 24-h span. The coordinated circadian regulation of sleep/wake, rest/activity, fasting/feeding, and catabolic/anabolic cycles is crucial for optimal health. Circadian rhythms in gene expression synchronize biochemical processes and metabolic fluxes with the external environment, allowing the organism to function effectively in response to predictable physiological challenges. In mammals, this daily timekeeping is driven by the biological clocks of the circadian timing system, composed of master molecular oscillators within the suprachiasmatic nuclei of the hypothalamus, pacing self-sustained and cell-autonomous molecular oscillators in peripheral tissues through neural and humoral signals. Nutritional status is sensed by nuclear receptors and coreceptors, transcriptional regulatory proteins, and protein kinases, which synchronize metabolic gene expression and epigenetic modification, as well as energy production and expenditure, with behavioral and light-dark alternance. Physiological rhythmicity characterizes these biological processes and body functions, and multiple rhythms coexist presenting different phases, which may determine different ways of coordination among the circadian patterns, at both the cellular and whole-body levels. A complete loss of rhythmicity or a change of phase may alter the physiological array of rhythms, with the onset of chronodisruption or internal desynchronization, leading to metabolic derangement and disease, i.e., chronopathology.

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Section: Adipose Tissue Humoral and Molecular Regulators And The CLmentioning

confidence: 99%

Clock Genes and Clock-Controlled Genes in the Regulation of Metabolic Rhythms

Mazzoccoli

Pazienza

Vinciguerra

2012

Chronobiology International

148

109

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“…The A1 adenosine receptor is a Gi-coupled receptor. Its activation by adenosine has an inhibitory effect on lipolysis and has also been shown to increase the production of leptin in isolated white adipocytes (3,4). The P2 purinergic receptors (P2X and P2Y) are activated by selective binding of nucleotides such as the purines adenosine mono-, bi-, and tri-phosphate (AMP, ADP, and ATP) or pyrimidines such as uracil bi-and tri-phosphate (UDP and UTP) (5).…”

mentioning

confidence: 99%

The Purinergic P2Y1 Receptor Supports Leptin Secretion in Adipose Tissue

Laplante

Monassier²,

Freund

et al. 2010

Endocrinology

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Extracellular nucleotides have been shown to trigger intracellular calcium release and influence leptin secretion in differentiated white and brown adipocytes through activation of various but not clearly identified P2 receptors. In the present study, we wished to assess whether or not the P2Y1 ADP receptor is functional in white adipocytes and whether it could affect the secretion of adipocyte-derived hormones. Stromal cells and mature adipocytes were isolated from epididymal adipose tissue from wild-type and P2Y1 knockout (KO) C57-black/six male mice. The expression of the P2Y1 receptor in adipocytes was confirmed by RT-PCR and intracellular calcium measurements with fura 2-AM. KO of P2Y1 receptors did not affect the cell size and lipid content of mature adipocytes or the differentiation of the stromal cell fraction, but the leptin production of mature adipocytes was decreased under basal and insulin-stimulated conditions. A selective P2Y1 antagonist, MRS2500, reduced leptin release in isolated adipocytes. The plasma and adipose tissue mRNA levels of leptin were also lower in P2Y1 KO mice as compared with wild-type animals. However, in mice fed a high-fat diet, the plasma leptin levels were greatly enhanced and the inhibitory effect of P2Y1 KO was not observed. These results show that the P2Y1 receptor supports leptin production in isolated white adipocytes through a transcriptional mechanism. This function of the receptor may regulate plasma leptin in lean mice but is overcome in obese animals.

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“…Furthermore, it is known that A1R activation mediates leptin secretion in animal models, 8 and blocking of the receptor or removal of endogenous adenosine reduces leptin secretion from isolated adipocytes. 9 The A1R also has a physiological role in protecting against obesity-related insulin resistance, 10 and agonism of the A1R has been shown to lower plasma-free fatty acids and glycerol in obese Zucker fatty animals. 7 Glucose-stimulated insulin and glucagon secretion were also elevated in A1R null mice when compared with wild-type animals.…”

Section: Introductionmentioning

confidence: 99%

Contrasting effects of A1 and A2b adenosine receptors on adipogenesis

et al. 2011

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Background: Adenosine mediates its actions through four G protein-coupled receptors, A1, A2a, A2b and A3. The A1 receptor (A1R) is dominant in adipocytes where it mediates many actions that include inhibition of lipolysis, stimulation of leptin secretion and protection against obesity-related insulin resistance. Objective: The objective of this study is to investigate whether induced expression of A1Rs stimulates adipogenesis, or whether A1R expression is a consequence of cells having an adipocyte phenotype. Methodology: Human A1R and A2b receptors (A2bRs) were stably transfected into a murine osteoblast precursor cell line, 7F2. Adipogenesis was determined by lipid accumulation and expression of adipocyte and osteoblast marker molecules. Adenosine receptor expression and activation of associated signal molecules were also evaluated as 7F2 cells were induced to differentiate to adipocytes. Results: 7F2 cells transfected with the A1R showed increased adipocyte marker mRNA expression; lipoprotein lipase and glycerol-3-phosphate dehydrogenase were both upregulated, whereas the osteoblast marker alkaline phosphatase (ALP) was downregulated. When cultured in adipocyte differentiating media, such cells also showed increased adipogenesis as judged by lipid accumulation. Conversely, A2bR transfection stimulated osteocalcin and ALP expression, and in addition, adipogenesis was inhibited in the presence of adipocyte differentiation media. Adipogenic differentiation of naive 7F2 cells also resulted in increased expression of the A1R and reduced or modified expression of the A2a and A2bR. The loss of A2 receptors after adipogenic differentiation was accompanied by a loss of cyclic adenosine monophosphate and ERK1/2 signalling. Conclusion: These data show that expression of A1Rs induced adipocyte differentiation, whereas A2bR expression inhibited adipogenesis and stimulated an osteoblastic phenotype. These data suggest that targeting A1 and A2bR could be considered in the management of obesity and diabetes. Targeting adenosine signal pathways may be useful in treatment strategies for diseases in which there is an imbalance between osteoblasts and adipocytes.

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Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats.

Cited by 42 publications

References 14 publications

Clock Genes and Clock-Controlled Genes in the Regulation of Metabolic Rhythms

Clock Genes and Clock-Controlled Genes in the Regulation of Metabolic Rhythms

The Purinergic P2Y1 Receptor Supports Leptin Secretion in Adipose Tissue

Contrasting effects of A1 and A2b adenosine receptors on adipogenesis

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