Adenosine A1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue — Interactions with insulin

Johansson, Stina; Lindgren, Eva; Yang, Jiangning; Herling, Andreas W.; Fredholm, Bertil B.

doi:10.1016/j.ejphar.2008.08.022

Cited by 106 publications

(85 citation statements)

References 56 publications

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“…We observed an age-dependent reduction in lean mass and an accumulation of VAT in wild-type but not in A 1 −/− mice. This is entirely compatible with previous studies showing that endogenous adenosine, through A 1 receptor signalling, reduces lipolysis and enhances lipogenesis [29]. We also found that advanced age was associated with elevated blood glucose levels, impaired glucose tolerance and insulin responses or signalling in A 1 +/+ but not in A 1 −/− mice.…”

Section: Discussionsupporting

confidence: 93%

Abrogation of adenosine A1 receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses

et al. 2015

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Aims/hypothesis Adenosine is an important regulator of metabolism; however, the role of the A 1 receptor during ageing and obesity is unclear. The aim of this study was to investigate the effects of A 1 signalling in modulating metabolic function during ageing. Methods Age-matched young and aged A 1 (also known as Adora1)-knockout (A 1 −/−) and wild-type (A 1 +/+ ) mice were used. Metabolic regulation was evaluated by body composition, and glucose and insulin tolerance tests. Isolated islets and islet arterioles were used to detect islet endocrine and vascular function. Oxidative stress and inflammation status were measured in metabolic organs and systemically. Results Advanced age was associated with both reduced glucose clearance and insulin sensitivity, as well as increased visceral adipose tissue (VAT)

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Section: Discussionsupporting

confidence: 93%

Abrogation of adenosine A1 receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses

et al. 2015

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“…Male A1R (À/À) mice (X5 months) were, surprisingly, significantly heavier than A1R-positive mice, although there was no apparent weight difference in younger animals. 21 These findings appear to contradict the earlier data of LaNoue and Martin 22 who showed a loss of A1R in genetically obese rodents. The A1R is also strongly linked with insulin in adipose tissue, as its activation inhibits insulin release 23 …”

Section: Discussionmentioning

confidence: 73%

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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“…For example, in white adipocytes isolated from murine epididymal WAT, basal lipolysis was increased more than sevenfold in the presence of ADA (0.1 U ml −1 ), and >18-fold in a combined treatment with ADA and noradrenaline (10 nmol l −1 ). In the absence of ADA, a more than ninefold increase was observed in response to noradrenaline (Johansson et al, 2008). These pro-lipolytic effects of ADA are owing to the clearance of adenosine, which inhibits adenylyl cyclase activity via ADORA1.…”

Section: Anti-lipolytic Effectors Adenosinementioning

confidence: 99%

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Braun

Oeckl

Westermeier

et al. 2018

Journal of Experimental Biology

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The enormous plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. In energy balance, lipolysis of triacylglycerols and re-esterification of free fatty acids are opposing processes operating in parallel at identical rates, thus allowing a more dynamic transition from anabolism to catabolism, and vice versa. In response to alterations in the state of energy balance, one of the two processes predominates, enabling the efficient mobilization or storage of energy in a negative or positive energy balance, respectively. The release of noradrenaline from the sympathetic nervous system activates lipolysis in a depot-specific manner by initiating the canonical adrenergic receptor-G s -protein-adenylyl cyclase-cyclic adenosine monophosphate-protein kinase A pathway, targeting proteins of the lipolytic machinery associated with the interface of the lipid droplets. In brown and brite adipocytes, lipolysis stimulated by this signaling pathway is a prerequisite for the activation of non-shivering thermogenesis. Free fatty acids released by lipolysis are direct activators of uncoupling protein 1-mediated leak respiration. Thus, pro-and anti-lipolytic mediators are bona fide modulators of thermogenesis in brown and brite adipocytes. In this Review, we discuss adrenergic and non-adrenergic mechanisms controlling lipolysis and thermogenesis and provide a comprehensive overview of pro-and anti-lipolytic mediators.

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Adenosine A1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue — Interactions with insulin

Cited by 106 publications

References 56 publications

Abrogation of adenosine A1 receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses

Abrogation of adenosine A1 receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses

Contrasting effects of A1 and A2b adenosine receptors on adipogenesis

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

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