Selenoproteins, as the active form of selenium, play an important role in various physiological and pathological processes, such as anti-oxidation, anti-tumor, immune response, metabolic regulation, reproduction and aging. Although the expression level of selenoproteins in adipose tissue is significantly influenced by dietary selenium intake, it is closely related to the homeostasis of adipose tissue. In this review, we summarized the role of selenoproteins in the physiological function of adipose tissue and the pathogenesis of obesity in recent years, in order to provide a rationale for developing potential therapeutic agents for the treatment of obesity and related metabolic diseases.
Selenoproteins/metabolism* ; Adipose Tissue/physiology* ; Obesity/metabolism* ; Humans ; Animals ; Selenium

BACKGROUND: Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD). METHODS: We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV). RESULTS: Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P<0.001). In multiple logistic regression analysis, the subjects in the highest SeP tertile showed a higher risk for NAFLD than those in the lowest SeP tertile, even after adjusting for potential confounding factors (odds ratio, 7.48; 95% confidence interval, 1.72 to 32.60; P=0.007). CONCLUSION: Circulating SeP levels were increased in subjects with NAFLD as well as in those with visceral obesity and may be a novel biomarker for NAFLD.
Adiponectin ; C-Reactive Protein ; Cholesterol ; Cholesterol, HDL ; Energy Metabolism ; Fatty Liver ; Homeostasis ; Humans ; Insulin Resistance ; Intra-Abdominal Fat ; Lipoproteins ; Liver ; Logistic Models ; Obesity ; Obesity, Abdominal ; Pulse Wave Analysis ; Risk Factors ; Rodentia ; Selenoprotein P ; Selenoproteins

BACKGROUNDTanis was reported as a putative receptor for serum amyloid A (SAA) involving glucose regulated protein in insulin regulated resistance. It was found to be dysregulated in diabetic rats (Psammomys obesus, Israeli sand rat) and its homologue for humans is SelS/AD-015. The present study analyzed mRNA expression of SelS in omental adipose tissue biopsies from patients with type 2 diabetes mellitus (T2DM), and age- and weight-matched nondiabetic patients, the relationship of SelS mRNA with Homa-IR and serum SAA level.

METHODSHuman omental adipose tissues from ten cases of type 2 diabetic patients and twelve cases of nondiabetic individuals were analyzed for the expression level of SelS mRNA by semiquantitative polymerase chain reaction (PCR), Homa-IR estimated by standard formula and SAA level by enzyme-linked immunosorbent assay (ELISA).

RESULTSSelS mRNA expression, Homa-IR and serum SAA were higher in T2DM sufferers than in nondiabetic control group. SelS mRNA level was positively correlated with Homa-IR and SAA level in each group.

CONCLUSIONSSelS protein may be involved in insulin resistance in Chinese with T2DM by acting as the SAA receptor, thus playing an important role in the development of T2DM and atherosclerosis.

Adipose Tissue ; metabolism ; Adult ; Aged ; Base Sequence ; Diabetes Mellitus, Type 2 ; metabolism ; Female ; Humans ; Insulin Resistance ; Male ; Membrane Proteins ; genetics ; Molecular Sequence Data ; Omentum ; metabolism ; RNA, Messenger ; analysis ; Selenoproteins ; genetics ; Serum Amyloid A Protein ; analysis

OBJECTIVEHuman selenoprotein P (HSelP) is unique protein that contains 10 selenocysteines encoded by 10 inframe UGA, which typically function as stop codon. The function of HSelP remains unclear, in part due to the inability to express it by gene recombinant technique. This study is to investigate expression and purification of recombinant HSelP in prokaryotic expression system, and its activity to induce apoptosis in vitro.

METHODSThe shorter HSelP isoform was cloned. After the selenocysteine (SeCys) at 40th position from N terminus of the HSelP shorter isoform was mutated into cysteine by PCR, it was expressed in E. coli. The expressed product was purified with DEAE column and identified by Western blot. Subsequently, its function on induction of mitochondrial apoptotic activity was studied.

RESULTSThe mutant HSelP shorter isoform expressed in prokaryotic system was purified by DEAE column to 90% homogeneity. The purified product, HSelP280m, induced the opening of mitochondrial permeability transition pore (PTP) and decreased the transmembrane potential in a dose-dependent manner. These events could be abolished by PTP specific inhibitors.

CONCLUSIONHSelP280m can induce the opening of mitochondrial PTP, which provides a basis for investigating the structure and function of recombinant HSelP.

Animals ; Apoptosis ; drug effects ; Cloning, Molecular ; Cysteine ; genetics ; Escherichia coli ; metabolism ; Humans ; Ion Channels ; drug effects ; Male ; Membrane Potentials ; drug effects ; Mice ; Mice, Inbred BALB C ; Mitochondria, Liver ; physiology ; Mitochondrial Membrane Transport Proteins ; Mutation ; Protein Isoforms ; Proteins ; genetics ; metabolism ; pharmacology ; Selenium ; Selenocysteine ; genetics ; Selenoprotein P ; Selenoproteins

OBJECTIVETo study the cell biological mechanism of sodium selenite improving insulin sensitivity in pubertal rats with insulin resistance.

METHODSThe content of inositol 1,4,5-trisphosphate (IP3) was examined by anion resin chromatography, and mRNA levels of phosphatidylinositol 3-kinase regulatory subunits (PI3Kp85 alpha) and Se-P were detected by RT-PCR in hepatocyte isolated from pubertal rats with insulin resistance.

RESULTSThe mRNA levels of Se-P and PI3Kp85 alpha and content of IP3 in isolated hepatocyte decreased in pubertal male rats with insulin resistance. The above indices increased and reached normal level in rats supplied with selenium. The response to insulin stimulation in isolated hepatocyte in rats with selenium supply was similar to that in the control group, and both groups had higher response than those with high-fat diet. Alone when inhibited by wortmannin, the concentration of IP3 increased slightly in rats with selenium supply, but still was lower than that in the control group.

CONCLUSIONSThese results indicate that the effect of selenium improving insulin sensitivity may be related to phosphatidylinositol PI3K signalling pathway. The effect of regulation of IP3 by selenium is not as effective as that by insulin, which may explain the difference of effect between selenium and insulin.

Animals ; Cell Separation ; Hepatocytes ; cytology ; metabolism ; Inositol 1,4,5-Trisphosphate ; analysis ; Insulin ; pharmacology ; Insulin Resistance ; Male ; Phosphatidylinositol 3-Kinases ; analysis ; Proteins ; analysis ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Selenoproteins ; Signal Transduction ; Sodium Selenite ; pharmacology