BACKGROUND: Adiponectin is a collagen-like plasma protein speci®cally synthesized in adipose tissue. Plasma adiponectin concentrations are decreased in obesity whereas it is adipose-speci®c. OBJECTIVE: To clarify the signi®cance of the genetic variations in adiponectin gene on its plasma concentrations and obesity. SUBJECTS: Two hundred and nineteen unrelated adult Japanese subjects (123 men and 96 women, age: 20 ± 83 y, BMI: 16 ± 43 kgam 2 ) including 77 obese subjects (BMI b 26.4 kgam 2 ). MEASUREMENT: Human adiponectin gene was isolated from PAC DNA pools. Mutations in the adiponectin gene were screened by direct sequencing or restriction-fragment polymorphism. The levels of plasma adiponectin were determined by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin gene spanned 17 kb on chromosome 3q27, consisting of three exons and two introns. Within 2.1 kb of the 5 H -¯anking region, there were two octamer elements present in the promoter of adipsin. Two nucleotide changes were identi®ed. One was a polymorphism (GaT) occurring in exon 2, and the other was a missense mutation (R112C) in exon 3. The mean plasma adiponectin levels of the subjects carrying G allele were low (GaG: 4.5 mgaml; GaT: 5.9 mgaml; and TaT: 6.3 mgaml), but were not statistically signi®cant. The allelic frequency between the obese and the non-obese showed no signi®cant difference. The subject carrying R112C mutation showed markedly low concentration of plasma adiponectin. CONCLUSION: Two nucleotide changes have been identi®ed in the adiponectin gene. GaT polymorphism in exon 2 was associated with neither plasma adiponectin concentrations nor the presence of obesity. A subject carrying missense mutation (R112C) showed markedly low plasma adiponectin concentration.
Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A proteasegenerated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age-and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age-and BMImatched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes. Diabetes 51:2325-2328, 2002
Galectins constitute a family of proteins that bind to -galactoside residues and have diverse physiological functions. Here we report on the identification of a galectin-like molecule, galectin-12, in a human adipose tissue cDNA library. The protein contained two potential carbohydrate-recognition domains with the second carbohydrate-recognition domain being less conserved compared with other galectins. In vitro translated galectin-12 bound to a lactosyl-agarose column far less efficiently than galectin-8. Galectin-12 mRNA was predominantly expressed in adipose tissue of human and mouse and in differentiated 3T3-L1 adipocytes. Caloric restriction and treatment of obese animals with troglitazone increased galectin-12 mRNA levels and decreased the average size of the cells in adipose tissue. The induction of galectin-12 expression by the thiazolidinedione, troglitazone, was paralleled by an increase in the number of apoptotic cells in adipose tissue. Immunocytochemical analysis revealed that galectin-12 was localized in the nucleus of adipocytes, and transfection with galectin-12 cDNA induced apoptosis of COS-1 cells. These results suggest that galectin-12, an adipose-expressed galectin-like molecule, may participate in the apoptosis of adipocytes.
Therapeutic effects of green tea involve an inhibitory function of its constituent polyphenol epigallocatechin gallate (EGCG) on cell signaling. The specificity and mechanism(s) by which EGCG inhibits cell signaling have remained unclear. Here, we demonstrate that green tea and EGCG induce suppressor of cytokine signaling 1 (SOCS1) gene expression, a negative regulator of specific cell signaling pathways. In mouse immune cells, EGCG induces SOCS1 expression via an oxidative (superoxide) pathway and activation of the signal transducer and activator of transcription 5 transcription factor. EGCG inhibited SOCS1-regulated cell signaling, but this inhibitory effect was abrogated in cells deficient in SOCS1. These findings identify a mechanism by which EGCG inhibits cell signaling with specificity, mediated by induction of the negative regulator SOCS1.
In the presence of a substoichiometric amount of a tert‐butoxy radical precursor and a base, alkylamides were found to be heteroarylated at their α‐C−H bonds with sulfonylheteroarenes through homolytic aromatic substitution, where a radical chain is operative.
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