Involvement of calcium-sensing receptor in inhibition of lipolysis through intracellular cAMP and calcium pathways in human adipocytes

He, Yonghan; Zhang, Huaqi; Teng, Jianghua; Huang, Lijie; Liu, Ying; Sun, Chongde

doi:10.1016/j.bbrc.2010.11.129

Cited by 41 publications

(36 citation statements)

References 33 publications

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“…After first describing the presence of the CaSR in human adipose cells (2), increasing evidence is being collected to establish its physiological role in this tissue. We observed an antilipolytic effect of its stimulation in isolated human adipocytes (28), which has been recently confirmed in the adipocyte cell line SW872 by He et al (29). These authors observed that the CaSR-elicited decline in lipolysis was associated with decreased cyclic AMP, protein kinase A activity, hormone sensitive lipase and adipose triglyceride lipase, all of which are key players in the lipolytic process.…”

Section: Discussionsupporting

confidence: 76%

Calcium sensing receptor activation elevates proinflammatory factor expression in human adipose cells and adipose tissue

Cifuentes

Fuentes

Tobar

et al. 2012

Molecular and Cellular Endocrinology

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We have previously established that human adipose cells and the human adipose cell line LS14 express the calcium sensing receptor (CaSR) and that its expression is elevated upon exposure to inflammatory cytokines that are typically elevated in obese humans. Research in recent years has established that an important part of the adverse metabolic and cardiovascular consequences of obesity derive from a dysfunction of the tissue, one of the mechanisms being a disordered secretion pattern leading to an excess of proinflammatory cytokines and chemokines. Given the reported association of the CaSR to inflammatory processes in other tissues, we sought to evaluate its role elevating the adipose expression of inflammatory factors. We exposed adipose tissue and in-vitro cultured LS14 preadipocytes and differentiated adipocytes to the calcimimetic cinacalcet and evaluated the expression or production of the proinflammatory cytokines IL6, IL1β and TNFα as well as the chemoattractant factor CCL2. CaSR activation elicited an elevation in the expression of the inflammatory factors, which was in part reverted by SN50, an inhibitor of the inflammatory mediator NFκB. Our observations suggest that CaSR activation elevates cytokine and chemokine production through a signaling pathway involving activation of NFκB nuclear translocation. These findings confirm the relevance of the CaSR in the pathophysiology of obesity-induced adipose tissue dysfunction, with an interesting potential for pharmacological manipulation in the fight against obesity- associated diseases.

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Section: Discussionsupporting

confidence: 76%

Calcium sensing receptor activation elevates proinflammatory factor expression in human adipose cells and adipose tissue

Cifuentes

Fuentes

Tobar

et al. 2012

Molecular and Cellular Endocrinology

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“…For cell culture we used the SW872 cell line (American Tissue Culture Collection, Rockville, MD, USA) that had been used in our previous study [19], cultured in DMEM/F-12 (3:1) containing 10% FBS and 1% penicillin/streptomycin in 5% CO 2 /95% air at 37°C [20]. Confluent monolayers of pre-adipocytes were induced to differentiate according to the method we previous used [19].…”

Section: Methodsmentioning

confidence: 99%

“…The detailed protocol for western blot in our laboratory has been described in a previous study [19]. Experiments were replicated at least three times and a representative blot was shown.…”

Section: Methodsmentioning

confidence: 99%

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Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial

et al. 2013

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Aims/hypothesis Increased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS). Methods A total of 100 obese women aged 33-51 years with BMI≥28 kg/m 2 and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (n=50) or identical placebo (n=50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes. CI 0.60, 3.44] in histidine supplementation group (n=45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppresses IL6 and TNF mRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB. Conclusions/interpretation Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes. Trial registration www.chictr.org/cn/ChiCTR-TRC-11001551Electronic supplementary material The online version of this article

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“…The low calcium diet also decreased protein levels of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase. Using the SW872 human adipose cell line, this CaSR-mediated antilipolytic effect was shown to rely on intracellular Ca 2+ augmentation, as well as a decrease in cyclic AMP (cAMP) and cAMP-dependent protein kinase A (PKA) signaling (He Y. et al, 2011). Similar results were obtained in primary human adipocytes, where CaSR activation decreased lipolysis via Giα protein and phosphoinositide 3 kinase (PI3K) signaling (Cifuentes and Rojas, 2008).…”

Section: Casr: a Role In Adipose Tissue Dysfunctionmentioning

confidence: 99%

Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications

Bravo-Sagua¹,

Mattar

Díaz

et al. 2016

Front. Physiol.

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Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue (WAT) is an active endocrine organ, with a crucial influence on whole-body homeostasis. WAT dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease, and some cancers. Among the regulators of WAT physiology, the calcium-sensing receptor (CaSR) has arisen as a potential mediator of WAT dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that CaSR activation in the visceral (i.e., unhealthy) WAT is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to CaSR activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in WAT plays a key role in the development of WAT dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that CaSR may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

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Involvement of calcium-sensing receptor in inhibition of lipolysis through intracellular cAMP and calcium pathways in human adipocytes

Cited by 41 publications

References 33 publications

Calcium sensing receptor activation elevates proinflammatory factor expression in human adipose cells and adipose tissue

Calcium sensing receptor activation elevates proinflammatory factor expression in human adipose cells and adipose tissue

Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial

Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications

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