title: Allosteric regulation of the calcium-sensing receptor in obese individuals.
abstract: 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.
authors.affiliation: National Key Discipline of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Yonghan
authors.initials: Y
authors.lastname: He
authors.forename: Ben
authors.initials: B
authors.lastname: Perry
authors.forename: Mingxin
authors.initials: M
authors.lastname: Bi
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000494:Allosteric Regulation; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000596:Amino Acids; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D044169:Receptors, Calcium-Sensing; D000242:Cyclic AMP; D002118:Calcium