National Key Discipline of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Int J Mol Med. 2013 Aug;32(2):511-8. doi: 10.3892/ijmm.2013.1408. Epub 2013 Jun 5.
We have previously reported that the calcium-sensing receptor (CaSR) plays an important role in modulating lipid metabolism under low calcium conditions. The aim of this study was to identify possible regulators of CaSR and the mechanisms of action of CaSR in obese individuals. Subcutaneous fat samples were obtained from 10 obese and 10 non-obese males undergoing elective abdominal surgery. Visceral fat pads were obtained from 12 obese and 12 non-obese male rats. Serum lipid, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations, as well as the gene and protein expression of CaSR in the white adipose tissue of obese subjects and rats were determined. Serum total calcium, vitamin D, parathyroid hormone (PTH) and amino acid levels in human subjects were measured. Intracellular calcium and cyclic adenosine monophosphate (cAMP) levels in rat adipocytes were measured by laser scanning confocal microscopy and ELISA, respectively. The results revealed that serum triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), TNF-α, IL-6 and PTH levels were significantly higher in the obese individuals versus the controls. By contrast, serum vitamin D and amino acid concentrations were lower in the obese individuals versus the controls. In addition, intracellular calcium levels were higher, while cAMP levels were lower in the obese rat adipocytes compared with the control group. However, the gene and protein expression of CaSR in white adipose tissue did not differ between the obese groups and the controls. Thus, these results suggest that CaSR functions not through its expression, but rather through allosteric regulation in obese individuals.
我们之前曾报道过钙敏感受体（CaSR）在低钙条件下调节脂质代谢中发挥着重要作用。本研究旨在确定 CaSR 的可能调节剂及其在肥胖个体中的作用机制。我们从 10 名接受择期腹部手术的肥胖男性和 10 名非肥胖男性中获得了皮下脂肪样本。从 12 名肥胖男性和 12 名非肥胖雄性大鼠中获得了内脏脂肪垫。测定了肥胖受试者和大鼠白色脂肪组织中 CaSR 的血清脂质、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）浓度以及基因和蛋白表达。测量了人类受试者血清总钙、维生素 D、甲状旁腺激素（PTH）和氨基酸水平。通过激光共聚焦显微镜和 ELISA 分别测定大鼠脂肪细胞内钙离子和环磷酸腺苷（cAMP）水平。结果表明，与对照组相比，肥胖组患者血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、TNF-α、IL-6 和 PTH 水平显著升高，而血清维生素 D 和氨基酸浓度则较低。此外，与对照组相比，肥胖大鼠脂肪细胞内钙离子水平升高，而 cAMP 水平降低。然而，白色脂肪组织中 CaSR 的基因和蛋白表达在肥胖组与对照组之间没有差异。因此，这些结果表明 CaSR 的功能不是通过其表达，而是通过肥胖个体的变构调节来实现的。
