scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Globular Adiponectin as a Complete Mesoangioblast Regulator: Role in Proliferation, Survival, Motility, and Skeletal Muscle Differentiation

15 Mar 2010-Molecular Biology of the Cell (American Society for Cell Biology)-Vol. 21, Iss: 6, pp 848-859
TL;DR: In vivo experiments confirm that globular adiponectin increases the survival, engraftment, and localization to muscle of mesoangioblasts in α-sarcoglycan-null mice.
Abstract: Mesoangioblasts are progenitor endowed with multipotent mesoderm differentiation ability. Despite the promising results obtained with mesoangioblast transplantation in muscle dystrophy, an improvement of their efficient engrafting and survival within damaged muscles, as well as their ex vivo activation/expansion and commitment toward myogenic lineage, is highly needed and should greatly increase their therapeutic potential. We show that globular adiponectin, an adipokine endowed with metabolic and differentiating functions for muscles, regulates vital cues of mesoangioblast cell biology. The adipokine drives mesoangioblasts to entry cell cycle and strongly counteracts the apoptotic process triggered by growth factor withdrawal, thereby serving as an activating and prosurvival stem cell factor. In addition, adiponectin provides a specific protection against anoikis, the apoptotic death due to lack of anchorage to extracellular matrix, suggesting a key protective role for these nonresident stem cells after systemic injection. Finally, adiponectin behaves as a chemoattractive factor toward mature myotubes and stimulates their differentiation toward the skeletal muscle lineage, serving as a positive regulator in mesoangioblast homing to injured or diseased muscles. We conclude that adiponectin exerts several advantageous effects on mesoangioblasts, potentially valuable to improve their efficacy in cell based therapies of diseased muscles.

Content maybe subject to copyright    Report

Citations
More filters
18 Mar 2013
TL;DR: It is shown that cells derived from embryonic endothelial progenitors are still maintained in the adult muscle and a treatment with a NO donor could influence them also in vivo.
Abstract: Mesoangioblasts (MABs) are multipotent progenitors with myogenic potential and able to cross endothelial barriers. MABs have been isolated from embryonic and adult vessels and, despite their current use in clinical trials, their developmental origin remains unclear. We have recently identified the in vivo counterpart of MABs as a subset of embryonic endothelial progenitors. Explaining the fate of these cells in normal adult skeletal muscle homeostasis and regeneration is mandatory to design tools to manipulate them in vivo. Nitric oxide (NO) has been shown to affect the behaviour of exogenous MABs and we investigated whether a treatment with a NO donor could influence them also in vivo. Here we show that cells derived from embryonic endothelial progenitors are still maintained in the adult muscle and

2 citations


Cites background from "Globular Adiponectin as a Complete ..."

  • ...The Pax7 expression domain is partially overlapping to that of Pax3 during the early epithelial dermomyotome stage [35, 36]....

    [...]

01 Jan 2014
TL;DR: In this paper, the beneficial metabolic effects of adiponectin which confer insulin-sensitizing and anti-diabetic effects are well established, and skeletal muscle is an important target tissue for adipone where it regulates glucose and fatty acid metabolism directly and via insulin sensitizing effects.
Abstract: The beneficial metabolic effects of adiponectin which confer insulin-sensitizing and anti-diabetic effects are well established. Skeletal muscle is an important target tissue for adiponectin where it regulates glucose and fatty acid metabolism directly and via insulin sensitizing effects. Cell surface receptors and the intracellular signaling events via which adiponectin orchestrates metabolism are now becoming well characterized. The initially accepted dogma of adiponectin action was that the physiological effects were mediated via endocrine effects of adipose-derived adiponectin. However, in recent years it has been established that skeletal muscle can also produce and secrete adiponectin that can elicit important functional effects. There is evidence that skeletal muscle adiponectin resistance may develop in obesity and play a role in the pathogenesis of diabetes. In summary, adiponectin acting in an autocrine and endocrine manner has important metabolic and insulin sensitizing effects on skeletal muscle which contribute to the overall anti-diabetic outcome of adiponectin action.
01 Jan 2012
TL;DR: The results reveal an unanticipated role for tissue macrophages in mesoangioblast function and should take into consideration coexisting inflammatory pathways, whose activation may prove crucial for its success.
Journal ArticleDOI
TL;DR: In this paper , the authors reviewed evidence surrounding the definition, etiology, and treatment of sarcopenic obesity with an emphasis on emerging regulatory nodes with therapeutic potential, and reviewed the available clinical evidence largely focused on diet, lifestyle, and behavioral interventions to improve quality of life.
Abstract: Sarcopenic obesity, or the loss of muscle mass and function associated with excess adiposity, is a largely untreatable medical condition associated with diminished quality of life and increased risk of mortality. To date, it remains somewhat paradoxical and mechanistically undefined as to why a subset of adults with obesity develop muscular decline, an anabolic stimulus generally associated with retention of lean mass. Here, we review evidence surrounding the definition, etiology, and treatment of sarcopenic obesity with an emphasis on emerging regulatory nodes with therapeutic potential. We review the available clinical evidence largely focused on diet, lifestyle, and behavioral interventions to improve quality of life in patients with sarcopenic obesity. Based upon available evidence, relieving consequences of energy burden, such as oxidative stress, myosteatosis, and/or mitochondrial dysfunction, is a promising area for therapeutic development in the treatment and management of sarcopenic obesity.
References
More filters
Journal ArticleDOI
01 Dec 2001-Methods
TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.

139,407 citations

Journal ArticleDOI
TL;DR: It is concluded that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy and that the replenishment of adiponECTin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
Abstract: Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.

4,845 citations

Journal ArticleDOI
TL;DR: It is shown that phosphorylation and activation of the 5′-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full- lengths Ad in the liver, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK.
Abstract: Adiponectin (Ad) is a hormone secreted by adipocytes that regulates energy homeostasis and glucose and lipid metabolism. However, the signaling pathways that mediate the metabolic effects of Ad remain poorly identified. Here we show that phosphorylation and activation of the 5'-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full-length Ad in the liver. In parallel with its activation of AMPK, Ad stimulates phosphorylation of acetyl coenzyme A carboxylase (ACC), fatty-acid oxidation, glucose uptake and lactate production in myocytes, phosphorylation of ACC and reduction of molecules involved in gluconeogenesis in the liver, and reduction of glucose levels in vivo. Blocking AMPK activation by dominant-negative mutant inhibits each of these effects, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK. Our data may provide a novel paradigm that an adipocyte-derived antidiabetic hormone, Ad, activates AMPK, thereby directly regulating glucose metabolism and insulin sensitivity in vitro and in vivo.

4,298 citations

Journal ArticleDOI
TL;DR: It is confirmed that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to thedegree of insulin resistance and hyperinsulinemia than to the level of adiposity and glucose intolerance.
Abstract: Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.

3,529 citations


"Globular Adiponectin as a Complete ..." refers background in this paper

  • ...The peculiarity of adiponectin compared with sphingosine 1-phosphate is that the adipokine is produced by adipose tissue in an inverse relationship with fat mass, and its level is strongly decreased in diabetic patients (Weyer et al., 2001; Rasouli and Kern, 2008)....

    [...]

Journal ArticleDOI
12 Jun 2003-Nature
TL;DR: The cloning of complementary DNAs encoding adiponectin receptors 1 and 2 by expression cloning supports the conclusion that they serve as receptors for globular and full-length adiponECTin, and that they mediate increased AMP kinase and PPAR-α ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectionin.
Abstract: Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.

3,013 citations

Related Papers (5)