Reconstruction of the anterior cruciate ligament: association of graft choice with increased risk of early revision.

We examined the association of graft type with the risk of early revision of primary anterior cruciate ligament reconstruction (ACLR) in a community-based sample. A retrospective analysis of a cohort of 9817 ACLRs recorded in an ACLR Registry was performed. Patients were included if they underwent primary ACLR with bone-patellar tendon-bone autograft, hamstring tendon autograft or allograft tissue. Aseptic failure was the main endpoint of the study. After adjusting for age, gender, ethnicity, and body mass index, allografts had a 3.02 times (95% confidence interval (CI) 1.93 to 4.72) higher risk of aseptic revision than bone-patellar tendon-bone autografts (p < 0.001). Hamstring tendon autografts had a 1.82 times (95% CI 1.10 to 3.00) higher risk of revision compared with bone-patellar tendon-bone autografts (p = 0.019). For each year increase in age, the risk of revision decreased by 7% (95% CI 5 to 9). In gender-specific analyses a 2.26 times (95% CI 1.15 to 4.44) increased risk of hamstring tendon autograft revision in females was observed compared with bone-patellar tendon-bone autograft. We conclude that allograft tissue, hamstring tendon autografts, and younger age may all increase the risk of early revision surgery after ACLR.

Ten-year hip fracture incidence rate trends in a large California population, 1997-2006.

UNLABELLED: Hip fractures are a large public health problem with significant negative impact on an individual's overall health and survival. But while the total numbers of persons affected by hip fractures may be anticipated to increase, incidence rates appear to be declining. INTRODUCTION: To describe annual hip fracture incidence rate trends in an integrated health-care organization over 1997-2006, during which a proactive bone health program was initiated program-wide and other secular trends occurred in the population. METHODS: For this ecologic trend study, we identified all men and women ≥45 years old as of January 1 of each year. Incident fractures for each year were identified using ICD-9 diagnosis codes 820-820.9, excluding all subjects who had fractures in prior years. Annual person-time at risk for hip fracture was determined from enrollment data. Sex- and age-specific and adjusted annual incidence rates were calculated. RESULTS: The overall annual hip fracture incidence rate for men declined from 1.52/1,000 person-years in 1997 to 1.29/1,000 person-years in 2006, a 15.3% (95% confidence interval [CI]=6.2-24.5) decrease. For women, incidence declined from 2.65/1,000 person-years in 1997 to 2.24/1,000 person-years in 2006, a 15.3% (95% CI=8.7-21.9) decrease. Among subjects aged 85 years or older, incidence rates for men declined from 27.0/1,000 to 18.9/1,000 person-years, and for women they declined from 32.7/1,000 to 27.1/1,000 person-years. CONCLUSION: Hip fracture incidence has been declining in all age groups over the past 10 years. While many factors may contribute to this decline, the results are consistent with a potential benefit of the active bone health intervention.

Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program.

AIMS: Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. METHODS: Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. RESULTS: Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ∼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. CONCLUSIONS: ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.

Insulin-mediated regulation of decidual protein induced by progesterone (DEPP) in adipose tissue and liver.

We analyzed the profile of the genes expressed in human adipose tissue and identified the fat-derived molecules, adiponectin and aquaporin 7, which modulate glucose and lipid metabolism. The same Bodymap analysis revealed abundant expression of the decidual protein induced by progesterone (DEPP) in the white adipose tissue. Northern blot analysis confirmed that human DEPP mRNA was highly expressed in white adipose tissue. Mouse DEPP mRNA was detected in heart, lung, skeletal muscle, and white adipose tissue under feeding state. In contrast, under fasting state, mouse DEPP mRNA was enhanced in lung, skeletal muscle, and white adipose tissue and it appeared also in the liver and kidney, suggesting up regulation of DEPP by fasting. Because fasting-induced DEPP expression was observed in insulin-sensitive organs, we investigated the regulation of DEPP in white adipose tissue and liver. During adipogenesis of mouse 3T3-L1 cells, DEPP mRNA increased in a differentiation-dependent manner similar to adiponectin and aquaporin 7. Treatment of cultured 3T3-L1 mature adipocytes, rat H4IIE, and human HepG2 hepatoma cells with insulin significantly decreased DEPP mRNA levels in dose- and time-dependent manners. IN VIVO experiments showed significant decrease of hepatic and adipose DEPP mRNA levels in refed mice, compared to fasted animals, and also showed significant increase in DEPP mRNA in streptozotocin-induced insulin-deficient diabetic mice. These results indicate that DEPP is a novel insulin-regulatory molecule expressed abundantly in insulin-sensitive tissues including white adipose tissue and liver.

mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action.

OBJECTIVE: To determine whether the mRNA concentrations of inflammation response genes in isolated adipocytes and in cultured preadipocytes are related to adipocyte size and in vivo insulin action in obese individuals. DESIGN: Cross-sectional inpatient study. SUBJECTS: Obese Pima Indians with normal glucose tolerance. MEASUREMENTS: Adipocyte diameter (by microscope technique; n=29), expression of candidate genes (by quantitative real-time PCR) in freshly isolated adipocytes (monocyte chemoattractant protein (MCP) 1 and MCP2, macrophage inflammatory protein (MIP) 1alpha, MIP1beta and MIP2, macrophage migration inhibitory factor (MIF), tumor necrosis factor alpha, interleukin (IL) 6 and IL8; n=22) and cultured preadipocytes (MCP1, MIP1alpha, MIF, IL6 and matrix metalloproteinase 2; n=33) from subcutaneous abdominal adipose tissue (by aspiration biopsy, n=34), body fat by dual-energy X-ray absorptiometry, glucose tolerance by 75 g oral glucose tolerance test and insulin action by euglycemic-hyperinsulinemic clamp (insulin infusion rate 40 mU m(-2) min(-1)) (all n=34). RESULTS: MIF was the only gene whose expression in both freshly isolated adipocytes and cultured preadipocytes was positively associated with adipocytes diameter and negatively associated with peripheral and hepatic insulin action (all P<0.05). In multivariate analysis, the association between adipocyte MIF mRNA concentrations and adipocytes diameter was independent of the percentage of body fat (P=0.03), whereas adipocyte MIF mRNA concentrations, but not adipocyte diameter, independently predicted peripheral insulin action. The mRNA expression concentrations of the MIF gene in adipocytes were not associated with plasma concentrations of MIF, but were negatively associated with plasma adiponectin concentrations (P=0.004). In multivariate analysis, adipocyte MIF RNA concentrations (P=0.03) but not plasma adiponectin concentrations (P=0.4) remained a significant predictor of insulin action. CONCLUSIONS: Increased expression of MIF gene in adipose cells may be an important link between obesity characterized by enlarged adipocytes and insulin resistance in normal glucose tolerant people.

Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet.

BACKGROUND: Obesity is a risk factor for acute pancreatitis (AP), but the molecular mechanism remains unclear. Adiponectin, an adipose tissue-derived secretory factor, has anti-inflammatory properties in addition to various biological functions, and its plasma concentrations are reduced in obese subjects. However, the role of adiponectin in AP has not been investigated. AIM: To determine the effects of adiponectin on AP. METHODS: We investigated the effects of adiponectin on experimental AP by using adiponectin-knockout (APN-KO) mice and adenovirus-mediated adiponectin over-expression. AP was induced by 10 hourly intraperitoneal injections of low-dose caerulein (10 microg/kg) after 2 week feeding of normal chow or a high-fat diet (HFD) in wild-type (WT) and APN-KO mice. We evaluated the severity of AP biochemically and morphologically. RESULTS: Low-dose caerulein treatment did not induce pancreatic damage in either WT or APN-KO mice under normal chow feeding. APN-KO mice, but not WT mice, fed a HFD and then treated with caerulein developed pancreatic damage and inflammation, accompanied by increased macrophage/neutrophil infiltration and upregulation of pro-inflammatory mediators such as tumour necrosis factor alpha in the pancreas. Adenovirus-mediated over-expression of adiponectin attenuated the severity of HFD/caerulein-induced AP in APN-KO mice. CONCLUSIONS: Adiponectin plays a protective role in caerulein-induced AP in HFD-fed mice.

Nafamostat is hydrolysed by human liver cytosolic long-chain acyl-CoA hydrolase.

Although the authors recently reported that nafamostat, a clinically used serine protease inhibitor, was mainly hydrolysed by carboxylesterase in human liver microsomes, the involvement of human liver cytosol has not been elucidated. The current study examined the in vitro metabolism of nafamostat with human liver cytosols. Kinetic analysis indicated that the Vmax and Km values in the liver cytosols were 9.82 nmolmin(-1) mg(-1) protein and 197 microM for a liver sample HL-1, and 15.1 nmolmin(-1) mg(-1) protein and 157 microM for HL-2, respectively. The Vmax/Km values in both cytosols were at least threefold higher than those in the corresponding microsomes. The liver cytosolic activity for nafamostat hydrolysis was inhibited by phenylmethylsulfonyl fluoride (PMSF) (43% inhibition at 100 microM), whereas diisopropyl fluorophosphate (DFP) and bis(p-nitrophenyl)phosphate (BNPP) failed to inhibit the activity. Furthermore, the hydrolytic activity was also reduced by palmitoyl-CoA (67% inhibition at 100 microM) but not by acetyl-CoA. Effects of PMSF, DFP and BNPP on cytosolic palmitoyl-CoA hydrolytic activity were comparable with those of the cytosolic nafamostat hydrolytic activity. In addition, the palmitoyl-CoA hydrolytic activity was competitively inhibited by nafamostat with the apparent Ki value of 164 microM for the liver cytosol from HL-2. These results suggest that an isoform of long-chain acyl-CoA hydrolase may be responsible for the nafamostat hydrolysis in human liver cytosol.

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.

Impact of glycerol gateway molecule in adipocytes.

Glycerol is one of the essential nutrients in the mammalian body. Glycerol released from adipocytes is delivered to the liver and used for gluconeogenesis. The molecular mechanism of glycerol transport across the cell membrane remains unclear. AQPadipose, which we identified in human adipose cDNA project and later found to be human AQP7, is expressed in adipose tissue, and upregulated during fasting. AQP7 belongs to the aquaglyceroporin subfamily to permealize glycerol as well as water. Loss of function mutation of AQP7 in human caused disturbance of normal rise of plasma glycerol. Disruption of AQP7 gene in mice resulted in profound hypoglycemia during prolonged fasting because of impaired glycerol supply to the liver. In obesity, AQP7 is overexpressed in visceral fat,accompanied by portal hyperglycerolemia and systemic hyperglycemia. Considered together, these works indicate that AQP7 functions as a glycerol gateway molecule in adipocytes.

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.

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.

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.

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.

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.

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.

Effects of soy protein diet on the expression of adipose genes and plasma adiponectin.

Many studies have reported the cholesterol-lowering, anti-lipogenic, anti-obesity and anti-hypertensive effects of soy protein. Adipose tissue-specific plasma protein, adiponectin, has anti-atherogenic and anti-insulin-resistance properties. Here, we investigated the effects of soy protein diet on body fat composition, plasma glucose, lipid and adiponectin levels and expression of genes involved in glucose and fatty acid metabolism in obese KK-A y mice. Body weights and adipose tissue weights of mesenteric, epididymal, and brown fat were lower in mice on calorie-restricted diet containing soy protein isolate. Plasma cholesterol, triglyceride, free fatty acid, and glucose levels were also decreased by this diet. Body fat content and plasma glucose levels in mice on a soy protein isolate diet were still lower than those treated with an isocaloric casein-protein-diet. Among the genes related to glucose and fatty acid metabolism, adiponectin mRNA levels in adipose tissue and adiponectin plasma concentrations were elevated in mice on a calorie-restricted diet, although there were no significant differences between soy protein and casein protein groups. Our results indicate that that soy protein diet decreased body fat content and plasma glucose levels more effectively than isocaloric casein-protein diet in obese mice.

Visceral fat is a major contributor for multiple risk factor clustering in Japanese men with impaired glucose tolerance.

OBJECTIVE: The significance of abdominal visceral fat accumulation was evaluated in Japanese men with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: The IGT subjects (n = 123) were aged 55 +/- 9 years with a BMI of 24 +/- 3 kg/m(2). The 148 control subjects with normal glucose tolerance (NGT) were matched for age and BMI. IGT and NGT were classified according to the 1985 World Health Organization criteria. Abdominal fat distribution was analyzed by computed tomography at umbilical level. Plasma lipid, glucose, and insulin concentrations and blood pressure (BP) were measured. RESULTS: In subjects with IGT, the average visceral fat area (VFA) was significantly greater than in subjects with NGT. Fasting insulin, the sum of insulin concentrations during an oral glucose tolerance test, insulin resistance according to a homeostasis model assessment for insulin resistance (HOMA-IR), systolic BP, and serum triglyceride were significantly higher, whereas the DeltaI(30-0)/DeltaG(30-0) was significantly lower, in subjects with IGT. Subjects with IGT and NGT were then divided into three subgroups according to the number of risk factors they possessed (dyslipidemia, hypertension, neither, or both). In both IGT and NGT subjects, BMI, VFA, subcutaneous fat area, fasting insulin, HOMA-IR, and insulin secretion of the homeostasis model assessment were significantly higher in the double-risk factor subgroup than in the no-risk factor subgroup, and VFA was a potent and independent variable in association with the presence of a double risk factor. CONCLUSIONS: Visceral fat accumulation is a major contributor for multiple risk factor clustering in Japanese men with IGT and NGT.

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.