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T Funahashi

Publications and source records attributed to T Funahashi.

At least 19 recordsLinked to original sources
PubMed2006

Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation.

Dysregulated production of adipocytokines may be involved in the development of atherosclerotic cardiovascular disease in metabolic syndrome and chronic kidney disease (CKD) associated with metabolic syndrome. The aim of this study was to determine the effects of treatment with angiotensin II (Ang II) type-1 receptor blocker (ARB) on the regulation of adipocytokines. Olmesartan, an ARB, significantly blunted the age- and body weight-associated falls in plasma adiponectin both in genetically and diet-induced obese mice, without affecting body weight, but had no effect on plasma adiponectin levels in lean mice. Olmesartan also ameliorated dysregulation of adipocytokines in obesity, such as tumor necrosis factor-alpha, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, and serum amyloid A3. Olmesartan significantly reduced reactive oxygen species originating from accumulated fat and attenuated the expression of nicotinamide adenine dinucleotide phospho hydrogenase oxidase subunits in adipose tissue. In cultured adipocytes, olmesartan acted as an antioxidant and improved adipocytokine dysregulation. Our results indicate that blockade of Ang II receptor ameliorates adipocytokine dysregulation and that such action is mediated, at least in part, by targeting oxidative stress in obese adipose tissue. Ang II signaling and subsequent oxidative stress in adipose tissue may be potential targets for the prevention of atherosclerotic cardiovascular disease in metabolic syndrome and also in metabolic syndrome-based CKD.

Adiponectin↗
PubMed2005

Changes in adiponectin receptor expression in muscle and adipose tissue of type 2 diabetic patients during rosiglitazone therapy.

AIMS/HYPOTHESIS: Adiponectin is important in the regulation of insulin sensitivity in man. Its receptors, adipoR1 and R2, have recently been identified, but their expression in adipose tissue and their regulation in response to insulin sensitisation of diabetic patients have never been assessed. We therefore explored the regulation of adipoR1/R2 and adiponectin expression in adipose tissue and skeletal muscle, and of adiponectin plasma concentrations in response to insulin sensitisation by rosiglitazone. METHODS: Patients with type 2 diabetes were studied in a double-blind, placebo-controlled crossover study, using in vivo arteriovenous techniques of measuring adipose tissue and muscle blood flow, combined with measurement of adipose tissue and skeletal muscle gene expression. RESULTS: Rosiglitazone treatment increased adiponectin concentrations by 69%. Skeletal muscle adipoR1 expression was down-regulated from 109.0 (70.1-165.7) (median [interquartile range]) to 82.8 (63.6-89.3) relative units (p=0.04), but adipose tissue adipoR1 expression was up-regulated from 5.3 (4.4-9.4) to 11.2 (4.8-15.3) relative units (p=0.02) by rosiglitazone. In contrast to adipoR1 expression, adipoR2 expression was not altered by rosiglitazone in either of the tissues. The increase in adipose tissue adipoR1 expression with rosiglitazone was associated with increased postprandial triglyceride clearance (r=0.67, p=0.05), and increased fasting fatty acid output (r=0.78, p=0.01) measured in subcutaneous adipose tissue. CONCLUSIONS/INTERPRETATION: AdipoR1 expression is up-regulated in adipose tissue but down-regulated in skeletal muscle by rosiglitazone. These data suggest that adipoR1 plays a role in mediating the effects of adiponectin in specific tissues in relation to insulin sensitisation.

Adipose Tissue↗
PubMed2005

Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease.

BACKGROUND AND AIMS: A characteristic feature of Crohn's disease (CD) is mesenteric adipose tissue hypertrophy. Mesenteric adipocytes or specific proteins secreted by them may play a role in the pathogenesis of CD. We recently identified adiponectin as an adipocyte specific protein with anti-inflammatory properties. Here we report on expression of adiponectin in mesenteric adipose tissue of CD patients. METHODS AND RESULTS: Mesenteric adipose tissue specimens were obtained from patients with CD (n = 22), ulcerative colitis (UC) (n = 8) and, for controls, colon carcinoma patients (n = 28) who underwent intestinal resection. Adiponectin concentrations were determined by enzyme linked immunosorbent assay, and adiponectin mRNA levels were determined by real time quantitative reverse transcription-polymerase chain reaction. Tissue concentrations and release of adiponectin were significantly increased in hypertrophied mesenteric adipose tissue of CD patients compared with normal mesenteric adipose tissue of CD patients (p = 0.002, p = 0.040, respectively), UC patients (p = 0.002, p = 0.003), and controls (p<0.0001, p<0.0001). Adiponectin mRNA levels were significantly higher in hypertrophied mesenteric adipose tissue of CD patients than in paired normal mesenteric adipose tissue from the same subjects (p = 0.024). Adiponectin concentrations in hypertrophied mesenteric adipose tissue of CD patients with an internal fistula were significantly lower than those of CD patients without an internal fistula (p = 0.003). CONCLUSIONS: Our results suggest that adipocytes in hypertrophied mesenteric adipose tissue produce and secrete significant amounts of adiponectin, which could be involved in the regulation of intestinal inflammation associated with CD.

Adipocytes↗
PubMed2004

Maternal soluble tumour necrosis factor receptor type 2 (sTNFR2) and adiponectin are both related to blood pressure during gestation and infant's birthweight.

OBJECTIVE: Tumour necrosis factor alpha (TNF-alpha) and adiponectin are strongly related to insulin sensitivity; insulin resistance of pregnancy is a major determinant of infant's birthweight. We aimed to study the contributions of maternal serum concentrations of soluble TNF-alpha receptors (sTNFR1 and sTNFR2) and adiponectin to infant's birthweight. DESIGN: Cross-sectional, hospital-based study of insulin sensitivity during gestation. PATIENTS: Fifty-one healthy women with uncomplicated pregnancy and delivery (except for elective Caesarian section) and their healthy newborn infants. measurements Maternal blood levels of glucose, insulin, glycosylated haemaglobin (HbA1c), sTNFR1, sTNFR2 and adiponectin at delivery; cord-blood levels of sTNFR1, sTNFR2 and adiponectin. RESULTS: At delivery, maternal sTNFR2 correlated with systolic blood pressure (SBP; r = 0.38, P = 0.005). In multiple regression analyses, SBP and HbA1c were independent predictors of sTNFR2, explaining 18 and 7% of its variance, respectively; insulin resistance index (HOMA-IR), body mass index at delivery and SBP were independent predictors of adiponectin, explaining 15, 8 and 7% of its variance, respectively. Both maternal sTNFR2 and SBP were negatively correlated with infant's birthweight (r = -0.28, P = 0.04 and r = -0.36, P = 0.01 respectively, adjusted for sex and gestational age). In multivariate regression analyses, infant's sex and either maternal sTNFR2 or adiponectin were independent predictors of infant's birthweight, each explaining between 6 and 9% of birthweight variance. Further addition of maternal SBP to these models revealed that this variable was the main predictor of infant's birthweight, explaining 13% of its variance. CONCLUSIONS: Maternal sTNFR2 and adiponectin are independently related to both maternal blood pressure and infant's birthweight in uncomplicated pregnancy. The contributions of the TNF-alpha system and adiponectin to hypertensive disorders of pregnancy and fetal growth merit further studies.

Adiponectin↗
PubMed2003

Plasma adiponectin concentration before and after successful kidney transplantation.

BACKGROUND: Adiponectin, a protein secreted exclusively by adipocytes, is presumed to be involved in the pathogenesis of atherosclerosis and insulin resistance. An elevated plasma adiponectin concentration was found in ESRD patients on hemodialysis (HD). However, the role of kidneys in adiponectin biodegradation/elimination is unknown. Therefore, we assessed plasma adiponectin concentrations in ESRD patients before and after successful kidney transplantation. METHODS: Among 44 hemodialyzed patients (29 men, 15 women; mean age 39 +/- 11 years; mean body mass index [BMI] 23.6 +/- 3.5 kg/m(2); mean duration of HD treatment before kidney transplantation 27 +/- 26 months), plasma adiponectin concentrations and insulin resistance indices (HOMA-R) were measured twice: immediately before kidney transplantation (Tx) and 1-2 days before patient discharge from the hospital with stable kidney transplant function (mean serum creatinine level 191 +/- 105 micromol/L). The control group consisted of 22 normotensive healthy subjects (12 men, 10 women). RESULTS: Among uremic patients, before Tx, plasma adiponectin concentrations were significantly higher than in healthy subjects (20.8 +/- 8.3 vs 8.7 +/- 4.8 microg/mL; P <.001) After successful Tx, plasma adiponectin concentrations decreased significantly (20.8 +/- 8.3 vs 15.7 +/- 7.0 microg/mL before and after Tx, respectively; P <.001). Simultaneously, after successful kidney transplantation, an increase in HOMA-R was observed (1.01 +/- 0.61 vs 1.43 +/- 0.83; P =.002). However, changes in adiponectinemia did not significantly correlate with serum creatinine or HOMA-R. CONCLUSION: The kidneys seem to play an important role in adiponectin biodegradation and/or elimination.

Adiponectin↗
PubMed2003

Plasma adiponectin levels in women with anorexia nervosa.

Adiponectin is a plasma protein exclusively secreted by adipose tissue, which plays a role in modulating lipid and glucose metabolism. The plasma adiponectin concentration shows an inverse correlation with the body mass index in normal and obese individuals, but it has not been investigated in subjects with an extremely low body weight and undernutrition such as anorexia nervosa patients. We investigated plasma adiponectin levels in 21 females with anorexia nervosa. Nineteen healthy females served as the lean control group. The subjects with anorexia nervosa had a significantly lower weight and showed a tendency towards higher adiponectin levels than the control group. No correlation between adiponectin and BMI was found in patients with anorexia nervosa, while a linear negative correlation was seen in lean controls. The patient who showed the lowest adiponectin level reached a life-threatening state and required intravenous feeding in hospital. In association with improved nutrition and weight gain, the adiponectin level increased gradually until the body mass index was about 16 and then decreased subsequently as would be expected in lean normal subjects. These observations suggest that adipose tissue secretes less adiponectin and the adiponectin levels do not show an inverse correlation simply with body mass index in some subjects with severe undernutrition.

Adiponectin↗
PubMed2003

Circulating adiponectin levels are reduced in nonobese but insulin-resistant first-degree relatives of type 2 diabetic patients.

Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic subjects (FDR) as well as 40 healthy control subjects (CON) without a known family history of diabetes. Insulin sensitivity (S(i)) was studied with the minimal model, and measurements of adiponectin, metabolic variables, inflammatory markers, and endothelial injury markers, as well as lipoprotein concentrations, were performed. FDR were insulin resistant (3.3 +/- 2.4 vs. 4.5 +/- 2.6 x 10(-4) x min(-1) per microU/ml [mean +/- SD], P < 0.01), and their circulating plasma adiponectin levels (6.6 +/- 1.8 vs. 8.1 +/- 3.0 microg/ml, P < 0.03) were decreased. After adjustments for age in FDR, adiponectin levels were negatively correlated with fasting proinsulin (r -0.64, P < 0.001), plasminogen activator inhibitor (PAI)-1 activity (r -0.56, P < 0.001), fasting insulin (r -0.55, P < 0.001), and acute insulin response (r -0.40, P < 0.05); they were positively related to HDL cholesterol (r 0.48, P < 0.01) and S(i) (r 0.41, P < 0.01). Furthermore, when adjusted for age, waist, and S(i), adiponectin was associated with HDL cholesterol and proinsulin, which explained 51% of the variation in adiponectin in multiple regression analyses in that group. In conclusion, circulating plasma adiponectin levels were decreased in nonobese but insulin-resistant FDR and, in addition, related to several facets of the insulin resistance syndrome (IRS). Thus, hypoadiponectinemia may be an important component of the association between cardiovascular disease and IRS.

Adiponectin↗
PubMed2001

Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue.

Adiponectin (ApN) is thought to play a major role in the pathogenesis of the Metabolic Syndrome. Production of ApN and regulation of its related gene (apM1) have not yet been studied in human visceral adipose tissue. ApN was mainly associated with adipocyte membranes and abundantly secreted in medium from isolated adipocytes. apM1 gene expression, restricted to the adipocyte fraction of adipose tissue, decreased spontaneously when adipose explants were cultured in basal medium for 24 h while the expression of other adipose genes barely changed (PPARgamma, GAPDH) or increased (PAI-1). Unexpectedly, the fall of apM1 mRNA was prevented by the addition of actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of protein synthesis, and by reducing the amount of adipose tissue cultured per dish, thereby suggesting that a newly synthesized factor released by adipose tissue destabilizes apM1 mRNA. apM1 gene expression was also negatively regulated by glucocorticoids and positively by insulin and IGF-1. This regulation could contribute to the decreased apM1/ApN levels in insulin-resistant patients with obesity and the Metabolic Syndrome.

Adipocytes↗
PubMed2001

Enhancement of the aquaporin adipose gene expression by a peroxisome proliferator-activated receptor gamma.

The current study demonstrates that aquaporin adipose (AQPap), an adipose-specific glycerol channel (Kishida, K., Kuriyama, H., Funahashi, T., Shimomura, I., Kihara, S., Ouchi, N., Nishida, M., Nishizawa, H., Matsuda, M., Takahashi, M., Hotta, K., Nakamura, T., Yamashita, S., Tochino, Y., and Matsuzawa, Y. (2000) J. Biol. Chem. 275, 20896-20902), is a target gene of peroxisome proliferator-activated receptor (PPAR) gamma. The AQPap mRNA amounts increased following the induction of PPARgamma in the differentiation of 3T3-L1 adipocytes. The AQPap mRNA in the adipose tissue increased when mice were treated with pioglitazone (PGZ), a synthetic PPARgamma ligand, and decreased in PPARgamma(+/-) heterozygous knockout mice. In 3T3-L1 adipocytes, PGZ augmented the AQPap mRNA expression and its promoter activity. Serial deletion of the promoter revealed the putative peroxisome proliferator-activated receptor response element (PPRE) at -93/-77. In 3T3-L1 preadipocytes, the expression of PPARgamma by transfection and PGZ activated the luciferase activity of the promoter containing the PPRE, whereas the PPRE-deleted mutant was not affected. The gel mobility shift assay showed the direct binding of PPARgamma-retinoid X receptor alpha complex to the PPRE. DeltaPPARgamma, which we generated as the dominant negative PPARgamma lacking the activation function-2 domain, suppressed the promoter activity in 3T3-L1 cells, dose-dependently. We conclude that AQPap is a novel adipose-specific target gene of PPARgamma through the binding of PPARgamma-retinoid X receptor complex to the PPRE region in its promoter.

3T3 Cells↗
PubMed2001

Genomic structure and insulin-mediated repression of the aquaporin adipose (AQPap), adipose-specific glycerol channel.

Aquaporin adipose (AQPap) is a putative glycerol channel in adipocytes (Kishida, K., Kuriyama, H., Funahashi, T., Shimomura, I., Kihara, S., Ouchi, N., Nishida, M., Nishizawa, H., Matsuda, M., Takahashi, M., Hotta, K., Nakamura, T., Yamashita, S., Tochino, Y., and Matsuzawa, Y. (2000) J. Biol. Chem. 275, 20896-20902). In the current study, we examined the genomic structure of the mouse AQPap gene and its regulation by insulin. The mouse AQPap gene spanned 12 kilobase pairs in chromosome 4 and consisted of 8 exons and 7 introns. The first two exons, designated exon 1 and exon 1', are alternatively spliced to common exon 2, and thus the AQPap gene possessed two potential promoters. The exon 1-derived transcript is dominant in both adipose tissues and adipocytes on the basis of RNase protection assay and promoter analysis. The mRNA increased after fasting and decreased with refeeding. Insulin deficiency generated by streptozotocin enhanced the mRNA in adipose tissue. Insulin down-regulated AQPap mRNA in 3T3-L1 adipocytes. The AQPap promoter contained heptanucleotide sequences, TGTTTTT at -443/-437, similar to the insulin-response element identified previously in the promoters of insulin-repressed genes. Deletion and single base pair substitution analysis of the promoter revealed that these sequences were required for insulin-mediated repression of AQPap gene transcription. The phosphatidylinositol 3-kinase pathway was involved in this inhibition. We conclude that insulin represses the transcription of AQPap gene via insulin response element in its promoter. Sustained up-regulation of AQPap mRNA in adipose tissue in the insulin-resistant condition may disturb glucose homeostasis by increasing plasma glycerol.

3T3 Cells↗
PubMed2001

Galectin-12, an Adipose-expressed Galectin-like Molecule Possessing Apoptosis-inducing Activity.

Galectins constitute a family of proteins that bind to beta-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.

3T3 Cells↗
PubMed2001

Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages.

BACKGROUND: Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. METHODS AND RESULTS: Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. CONCLUSIONS: The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.

Adipocytes↗
PubMed2001

Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation--double-blind placebo-controlled trial.

BACKGROUND: It has been clarified that visceral fat accumulation leads to atherosclerosis through multiple risk factors such as insulin resistance, glucose intolerance, hyperlipidemia and hypertension. So far, it has been reported that a thaizolidinedione derivative, troglitazone, improves the insulin resistance in subjects with diabetes, glucose intolerance and obesity. However, it has not been reported yet that troglitazone affects fat distribution in subjects concomitant with visceral fat accumulation and multiple risk factors. METHODS: Twenty-nine subjects with visceral fat accumulation who had at least two risk factors including glucose intolerance, hyperlipidemia and hypertension were investigated. They were randomly assigned to receive either 200 or 400 mg per day of troglitazone or placebo for 12 weeks. A 75 g oral glucose tolerance test (OGTT) was performed before and after the treatment for 12 weeks. Fasting plasma glucose, insulin, HbA(1c), total serum cholesterol (T-chol), triglyceride (TG), HDL-cholesterol (HDL-C), and blood pressure, as well as the number of risk factors were measured periodically during the treatment. The change of the abdominal fat distribution was evaluated using computed tomographic scanning (CT scan) at the umbilicus level. RESULTS: After the treatment for 12 weeks, the area under the curve (AUC) of plasma glucose from a 75 g OGTT decreased dose-dependently. HbA(1c) and TG decreased significantly in the high-dose troglitazone group (400 mg per day) compared with the placebo group (P<0.05). Systolic blood pressure was significantly lower in subjects with hypertension in the pooled troglitazone group than in the placebo group (P<0.05). Therefore, the number of risk factors decreased with the troglitazone treatment. The ratio of visceral fat area (VFA) to subcutaneous fat area (SFA) (V/S ratio) decreased in the troglitazone groups due to decreased VFA and increased SFA. CONCLUSION: These results suggest that thiazolidinedione derivative may be a useful drug to improve multiple risk factors by changing the fat distribution in subjects with visceral fat accumulation.

Adipose Tissue↗
PubMed2001

The expression of SPARC in adipose tissue and its increased plasma concentration in patients with coronary artery disease.

OBJECTIVE: Adipocytes secrete various cytokines and matrix proteins. Several of them precipitate in obesity-associated diseases, including atherosclerosis. In the current study, we have examined the expression of secreted protein, acidic and rich in cysteine (SPARC) in adipose tissue and its significance in obesity and coronary artery disease (CAD). RESEARCH METHODS AND PROCEDURES: The SPARC mRNA expressions both in vivo and in vitro were detected by Northern blot analysis. Plasma SPARC concentrations were measured by enzyme immunosorbent assay. First, we investigated the plasma SPARC levels of 88 unrelated adult Japanese subjects (62 men and 26 women; average age: [+/- SD] 50 +/- 12 years; body mass index [BMI]: 16 to 46 kg/m(2)). Additionally 31 subjects with CAD diagnosed by coronary angiography (20 men and 11 women) were also investigated. RESULTS: Human adipose tissues expressed abundant SPARC mRNA. SPARC expression in adipose tissues was upregulated in obese db/db mice. Markedly enhanced expression of SPARC mRNA was observed in 3T3-L1 fibroblasts during adipocyte differentiation. Consistent with these results, plasma SPARC levels proved a positive correlation with BMI in humans (r = 0.27; p < 0.01). Interestingly, plasma SPARC concentrations were significantly elevated in age- and BMI-matched subjects with CAD (p < 0.05). DISCUSSION: SPARC was expressed in adipose tissues and its expression was enhanced in obese mice. In human, plasma SPARC levels were elevated in obesity and CAD patients. This elevated SPARC may be involved in the progression of CAD.

Adipose Tissue↗
PubMed2001

Identification and characterization of the sodA genes encoding manganese superoxide dismutases in Vibrio parahaemolyticus, Vibrio mimicus, and Vibrio vulnificus.

Sequencing of Fur titration assay-positive clones obtained from genomic DNA libraries of Vibrio parahaemolyticus, V. mimicus and V. vulnificus revealed open reading frames encoding proteins of 202, 205 and 202 amino acid residues, respectively. Each open reading frame was preceded by a predicted Fur box which overlaps a likely promoter with similarity to the -10 and -35 consensus sequence of Escherichia coli. The deduced amino acid sequences shared considerable homology with bacterial Mn-containing superoxide dismutases (MnSODs). Consistent with this, these Vibrio strains produced proteins with SOD activity resistant to inhibition by H2O2 and KCN only when grown under iron-limiting conditions. Primer extension analysis of the total RNA from these vibrios revealed iron-repressible expression of the genes. Furthermore, when grown under iron-limiting conditions, E. coli carrying a plasmid with each cloned gene overexpressed protein with the same electrophoretic mobility and insensitivity of SOD activity to H2O2 and KCN. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by N-terminal amino acid sequencing revealed that proteins (MnSODs) having N-terminal amino acid sequences consistent with those deduced from the corresponding genes were present in cell lysates of the vibrios grown under these iron-limited conditions. These results demonstrate that the genes cloned in this study are sodA homologs encoding MnSODs, whose expression is regulated by the iron status of the growth medium. PCR using a primer set based on the V. parahaemolyticus sodA sequence revealed the presence of homologous genes in certain other Vibrio species.

Amino Acid Sequence↗
PubMed2001

Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.

Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.

Adiponectin↗
PubMed2001

Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin.

Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as atherosclerosis, against which it may confer protection. In this study, we observed the changes of plasma adiponectin levels with body weight reduction among 22 obese patients who received gastric partition surgery. A 46% increase of mean plasma adiponectin level was accompanied by a 21% reduction in mean body mass index. The change in plasma adiponectin levels was significantly correlated with the changes in body mass index (r = -0.5, P = 0.01), waist (r = -0.4, P = 0.04) and hip (r = -0.6, P = 0.0007) circumferences, and steady state plasma glucose levels (r = -0.5, P = 0.04). In multivariate linear regression models, the increase in adiponectin as a dependent variable was significantly related to the decrease in hip circumference (beta = -0.16, P = 0.028), after adjusting body mass index and waist circumference. The change in steady state plasma glucose levels as a dependent variable was related to the increase of adiponectin with a marginal significance (beta = -0.92, P = 0.053), after adjusting body mass index and waist and hip circumferences. In conclusion, body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin. In addition, the increase in plasma adiponectin despite the reduction of the only tissue of its own synthesis suggests that the expression of adiponectin is under feedback inhibition in obesity.

Adiponectin↗