Calcium sensing receptor effects in adipocytes and liver cells: Implications for an adipose-hepatic crosstalk

Villarroel, Pía; Mattar, Pamela; D'Espessailles, Amanda; Arrese, Marco; Arreguín, Andrea; Fuentes, Cecilia; Reyes, Marcela; Cifuentes, Mariana

doi:10.1016/j.abb.2016.08.017

Cited by 8 publications

(13 citation statements)

References 32 publications

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“…CASR gene is a G-protein-coupled receptor that plays a critical role in lipid metabolism 23 . Recent studies found that CASR has higher expression in obese patients 33 , and reported that CASR promotes TAG production via affecting the activity of the microsomal triglyceride transfer protein for VLDL secretion in liver 27 – 29 , 31 , 32 . Furthermore, recent studies indicated that CASR stimulation significantly elevated TAG synthesis in hepatocytes by facilitating the uptake of long-chain fatty acids 33 , 58 , 59 .…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies found that CASR has higher expression in obese patients 33 , and reported that CASR promotes TAG production via affecting the activity of the microsomal triglyceride transfer protein for VLDL secretion in liver 27 – 29 , 31 , 32 . Furthermore, recent studies indicated that CASR stimulation significantly elevated TAG synthesis in hepatocytes by facilitating the uptake of long-chain fatty acids 33 , 58 , 59 . These results indicate that miR-27a-5p may increase fat deposition partly by targeting CASR in steers via facilitating the production of TAG and the secretion of TAG as VLDL in the liver 31 – 33 , 55 – 59 .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, recent studies indicated that CASR stimulation significantly elevated TAG synthesis in hepatocytes by facilitating the uptake of long-chain fatty acids 33 , 58 , 59 . These results indicate that miR-27a-5p may increase fat deposition partly by targeting CASR in steers via facilitating the production of TAG and the secretion of TAG as VLDL in the liver 31 – 33 , 55 – 59 .…”

Section: Discussionmentioning

confidence: 99%

“…CASR not only functions in adipose tissue 29 , 30 , but also directly and indirectly affects peripheral organs such as the liver 31 . Recent studies indicated that CASR plays a critical role in the regulation of triglyceride production by affecting the activity of the microsomal triglyceride transfer protein 32 , 33 .…”

Section: Introductionmentioning

confidence: 99%

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MiR-27a-5p Increases Steer Fat Deposition Partly by Targeting Calcium-sensing Receptor (CASR)

Tang

Wang

Zan

2018

Sci Rep

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Castration increases fat deposition, improving beef quality in cattle. Here, the steer group exhibited a significantly higher intramuscular fat (IMF) content than the bull group. To determine the potential roles of microRNAs (miRNAs) in castration-induced fat deposition, differential expression patterns of miRNA in liver tissue were investigated in bulls and steers. A total of 7,827,294 clean reads were obtained from the bull liver library, and 8,312,483 were obtained from the steer liver library; 452 conserved bovine miRNAs and 20 novel miRNAs were identified. The results showed that the expression profiles of miRNA in liver tissue were changed by castration, and 12 miRNAs that were differentially expressed between bulls and steers were identified. Their target genes were majorly involved in the metabolic, PI3K-Akt, and MAPK signaling pathways. Furthermore, six differentially expressed miRNAs were validated by quantitative real-time PCR, and luciferase reporter assays verified that calcium-sensing receptor (CASR) was the direct target of miR-27a-5p. Meantime, we found that the expression level of CASR was significantly higher in steers than in bulls, and revealed that CASR gene silencing in bovine hepatocytes significantly inhibited triacylglycerol (TAG) accumulation and reduced secretion of very low density lipoprotein (VLDL). These results obtained in the liver indicate that miR-27a-5p may increase fat deposition partly by targeting CASR in steers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MiR-27a-5p Increases Steer Fat Deposition Partly by Targeting Calcium-sensing Receptor (CASR)

Tang

Wang

Zan

2018

Sci Rep

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“…Single nucleotide polymorphisms (SNPs) of calcium-sensing receptor gene ( CASR ) are predominantly associated with phenotypes of primary [4] and secondary hyperparathyroidism [5–8], and with idiopathic calcium nephrolithiasis [9, 10]. However, CASR expression is shown not only in parathyroid glands [11] and kidney tubules [10], but also in vascular smooth muscle cells [12], adipocytes and their progenitor cells [13, 14], human omental tissue [14], and hepatocytes [14, 15]. It is suggested that livers from obese patients may express higher levels of CASR transcripts [14].…”

Section: Introductionmentioning

confidence: 99%

Calcium-sensing receptor gene (CASR) polymorphisms and CASR transcript level concerning dyslipidemia in hemodialysis patients: a cross-sectional study

et al. 2019

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BackgroundThere is scarce data on CASR associations with dyslipidemia. We investigated in hemodialysis (HD) patients whether CASR single nucleotide polymorphisms (SNPs) rs7652589 and rs1801725 have associations with dyslipidemia and show epistatic interactions with SNPs of the energy homeostasis-associated gene (ENHO), retinoid X receptor α gene (RXRA), and liver X receptor α gene (LXRA).MethodsThe study included 1208 HD subjects. For diagnosis of dyslipidemia, both K/DOQI criteria and atherogenic index ≥3.8 were used. CASR rs1801725 was genotyped by TaqMan SNP Genotyping Assay, other SNPs – by high-resolution melting curve analysis or polymerase chain reaction-restriction fragment length polymorphism, as appropriate. Relative transcript levels of CASR, ENHO, RXRA, and LXRA were measured in peripheral blood mononuclear cells. The occurrence of dyslipidemic phenotypes concerning tested polymorphisms was compared using models of inheritance. Haplotypes were estimated using the Haploview 4.2 software. Epistatic interactions between tested SNPs were analyzed using the logistic regression and epistasis option in the PLINK software.ResultsRs7652589 indicated a greater probability of atherogenic dyslipidemia in the dominant inheritance model (OR 1.4, 95%CI 1.0–2.0, P = 0.026), principally because of increased triglyceride (TG) levels. The rs1801725 variant allele was associated with a decreased probability of dyslipidemia characterized by non-HDL-cholesterol ≥130 mg/dL and TG ≥200 mg/dL (OR 0.6, 0.4–0.9, P = 0.012). There were no epistatic interactions between CASR and RXRA, LXRA, and ENHO regarding dyslipidemia. Both rs7652589 and rs1801725 SNPs were not in linkage disequilibrium (D’ = 0.091, r2 = 0.003 for the entire HD group) and their haplotypes did not correlate with dyslipidemia. Relative CASR transcript was lower at a borderline significance level in patients harboring the rs1801725 variant allele compared with homozygotes of the major allele (0.20, 0.06–7.80 vs. 0.43, 0.04–5.06, P = 0.058). CASR transcript correlated positively with RXRA transcript (adjusted P = 0.001), LXRA transcript (adjusted P = 0.0009), ENHO transcript (borderline significance, adjusted P = 0.055), dry body weight (adjusted P = 0.035), and renal replacement therapy duration (adjusted P = 0.013).ConclusionsCASR polymorphisms (rs7652589, rs1801725) are associated with dyslipidemia in HD patients. CASR correlates with RXRA, LXRA, and ENHO at the transcript level. Further investigations may elucidate whether other CASR SNPs contribute to associations shown in this study.

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Autophagy mediates calcium-sensing receptor-induced TNFα production in human preadipocytes

Mattar

Bravo-Sagua

Tobar

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Obesity is a major current public health problem worldwide due to the severe co-morbid conditions that this disease entails. The development of obesity-related cardiometabolic disorders is in direct association with adipose tissue inflammation that leads to its functional impairment. Activation of the Calcium-Sensing Receptor (CaSR) in adipose tissue contributes to inflammation and adipose dysfunction. Autophagy, a process of cell component degradation, is closely related to inflammation in many diseases, however, whether autophagy is associated with CaSR-induced inflammation remains unknown. Using LS14 and SW872 preadipose cell lines as well as primary human preadipocytes, we show that CaSR activation with the allosteric activator cinacalcet induces autophagosome formation. Cinacalcet-induced LC3II content elevation was precluded by knockdown of the CaSR and enhanced by CaSR overexpression, indicating a specific effect. Autophagy inhibition using 3-methyladenine prevented CaSR-induced TNFα production, indicating that autophagy contributes to CaSR-induced inflammation in human preadipocytes. Our results suggest that modulation of CaSR-induced autophagy is an attractive target in obese inflamed adipose tissue, to prevent the development of diseases triggered by adipose dysfunction. We describe a novel mechanism and possible new target to modulate and prevent adipose inflammation and hence the resulting disease-generating adipose tissue dysfunction.

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Calcium sensing receptor effects in adipocytes and liver cells: Implications for an adipose-hepatic crosstalk

Cited by 8 publications

References 32 publications

MiR-27a-5p Increases Steer Fat Deposition Partly by Targeting Calcium-sensing Receptor (CASR)

MiR-27a-5p Increases Steer Fat Deposition Partly by Targeting Calcium-sensing Receptor (CASR)

Calcium-sensing receptor gene (CASR) polymorphisms and CASR transcript level concerning dyslipidemia in hemodialysis patients: a cross-sectional study

Autophagy mediates calcium-sensing receptor-induced TNFα production in human preadipocytes

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