Adiponectin In White Adipose Tissue Research Articles

Analysis of anti-obesity and anti-diabetic effects of acacia bark-derived proanthocyanidins in type 2 diabetes model KKAy mice.

The acacia bark extract derived from Acacia mearnsii De Wild is rich in proanthocyanidins, whose constituent units are robinetinidol, fisetinidol, catechin, and gallocatechin. In this study, we examined the effect of proanthocyanidins on obesity and diabetes using KKAy mice, a type 2 diabetes model. KKAy mice were fed either a low-fat diet, a high-fat diet, or a high-fat diet mixed with an acacia bark extract, a proanthocyanidins fraction, and other fraction for 7weeks. Monitoring the changes in the body weight revealed that acacia bark extract and proanthocyanidins fraction could prevent excessive weight gain resulting from a high-fat diet. In addition, increases in the fasting blood glucose level due to high-fat diet intake were found to be suppressed by acacia bark extract and proanthocyanidins fraction. Furthermore, proanthocyanidins derived from acacia bark were found to increase the expression of adiponectin in white adipose tissue, which enhances the action of insulin. In addition, acacia bark-derived proanthocyanidins suppressed gluconeogenesis and fatty acid synthesis in the liver, as well as suppressing the decrease in energy production under pathological conditions in skeletal muscle. In addition, acacia bark-derived proanthocyanidins showed AMPK activation and DPP-4 inhibitory action. Therefore, it was suggested that acacia bark-derived proanthocyanidins lowered fasting blood glucose levels through the above mechanism. These results suggest that proanthocyanidins derived from acacia bark are the active ingredients of the anti-obesity and anti-diabetic effects of acacia bark extract.

Aurantio-obtusin improves obesity and insulin resistance induced by high-fat diet in obese mice.

Aurantio-obtusin (AUR) is the main bioactive compound among the anthraquinones, from Cassia seed extract. This study was conducted to identify whether AUR could improve obesity and insulin resistance, induced by a high-fat diet in obese mice. Mice were fed a high-fat diet for 6 weeks and were then assigned to the high-fat diet (HFD) control group, the AUR 5 mg/kg group, or the AUR 10 mg/kg group. AUR improves glucose by activating the expression of PI3K, Akt and GLUT4, GLUT2. AUR altered the expression levels of several lipid metabolism-related and adipokine genes. AUR decreased the mRNA expression of PPAR-γ, FAS and increased the mRNA expression of PPAR-α in liver. AUR lowered SREBP-1c, FAS, SCD-1, inflammatory cytokines, and increased the expression of PPAR-γ, PPAR-α, CPT-1, and adiponectin in white adipose tissue (WAT). AUR docking with the insulin receptor showed that the residues of the insulin receptor, ectodomain, were the same as those around the emodin. The effect of AUR may be elicited by regulating the activity of the insulin signaling pathway, expression of lipid metabolism-related genes, and expression of inflammatory cytokine markers to improve adiposity, insulin resistance, and dyslipidemia.

Low-protein diet enhances adiponectin secretion in rats.

Previous studies including ours have shown that a low-protein diet up-regulates insulin signaling in the liver and muscle and induces fatty liver in rats. Adiponectin is known as an insulin-sensitizing adipocytokine. We, therefore, examined the effect of a low-protein diet on the adiponectin levels in rats. The low-protein diet significantly increased serum adiponectin level. However, mRNA and protein levels of adiponectin in white adipose tissue (WAT) were not changed by the low-protein diet. Since it is known that oligomerization is important to control serum adiponectin level, we examined the population of adiponectin oligomeric forms in WAT and found that low-protein diet did not change it. Despite these events, the amount of its secretion was significantly increased in the adipocytes isolated from WAT of low-protein diet-fed rats. These results indicate that a low-protein diet enhances adiponectin secretion, which is not due to the increased intracellular amount and oligomerization of adiponectin.

Inhibition of prolyl hydroxylase domain (PHD) by JTZ-951 reduces obesity-related diseases in the liver, white adipose tissue, and kidney in mice with a high-fat diet

The epidemic of obesity and its complications is rapidly increasing worldwide. Recent drug discoveries established the utility of prolyl hydroxylase domain (PHD) inhibitors as stabilizers of hypoxia-inducible factors (HIFs) in vivo, which are currently in human clinical studies for the treatment of anemia in chronic kidney disease (CKD). These studies suggest a role for PHD inhibitors in ameliorating obesity and hyperlipidemia. We hypothesized that HIF activation using a PHD inhibitor, JTZ-951, protects from obesity-related diseases in the white adipose tissue (WAT), liver, and kidney in mice fed with high-fat diet (HFD). Eight-week-old, C57BL/6J mice were fed with HFD for 20 weeks with or without JTZ-951(0.005%; mixed in chow). Body weight and plasma non-high-density lipoprotein (HDL) cholesterol levels were significantly lower in the JTZ-951 group as compared with the vehicle group. PHD inhibition improved liver steatosis, macrophage infiltration into WAT and adipocyte fibrosis. In the kidney, PHD inhibition reduced albuminuria. Histologically, the number of F4/80- positive infiltrating macrophages and mesangial expansion were milder in the JTZ-951 group. Relative mRNA expression of adiponectin in WAT was higher in the JTZ-951-treated group and inversely correlated with hepatic steatosis score, adipocyte macrophage aggregation, and albuminuria. Activation of HIF ameliorates multiple obesity-related consequences in mice with HFD. The results of the present study offer the promising view that pharmacological PHD inhibition may be beneficial for the treatment of obesity-related diseases that can be ameliorated by weight loss.

Caffeine upregulates hepatic SHBG production by increasing adiponectin in white adipose tissue

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Western diet triggers Toll-like receptor 4 signaling-induced endothelial dysfunction in female Wistar rats.

Overconsumption of a diet rich in fat and carbohydrates, called the Western diet, is a major contributor to the global epidemic of cardiovascular disease. Despite previously documented cardiovascular protection exhibited in female rats, this safeguard may be lost under certain metabolic stressors. We hypothesized that female Wistar rats challenged by a Western diet composed of 21% fat and 50% carbohydrate (34.1% sucrose) for 17 wk would develop endothelial dysfunction via endothelial Toll-like receptor 4 (TLR4) signaling. Western diet-fed female rats exhibited dysregulation of metabolism, revealing increased body weight and abdominal fat, decreased expression of adiponectin in white adipose tissue, glucose intolerance, and impaired insulin sensitivity. Western diet exposure increased hepatic triglycerides and cholesterol alongside hepatic steatosis, categorizing nonalcoholic fatty liver disease. Moreover, a Western diet negatively affected vascular function, revealing hypertension, impaired endothelium-dependent vasorelaxation, aortic remodeling, and increased reactive oxygen species (ROS) production. Aortic protein expression of TLR4 and its downstream proteins were markedly increased in the Western diet-fed group in association with elevated serum levels of free fatty acids. In vitro experiments were conducted to test whether free fatty acids contribute to vascular ROS overproduction via the TLR4 signaling pathway. Cultured endothelial cells were stimulated with palmitate in the presence of TAK-242, a TLR4 signaling inhibitor. Palmitate-induced overgeneration of ROS in endothelial cells was abolished in the presence of TAK-242. Our data show that a Western diet induced endothelial dysfunction in female rats and suggest that endothelial TLR4 signaling may play a key role in abolishing female cardiovascular protection. NEW & NOTEWORTHY A Western diet induced elevated levels of free fatty acids, produced nonalcoholic fatty liver disease, and provoked endothelial dysfunction in female rats in association with Toll-like receptor 4 signaling-mediated vascular reactive oxygen species production. Limited consumption of a Western diet in premenopausal women may decrease their risk of cardiovascular complications.

Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1), tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT) was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs) and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results indicate that irbesartan improves stress-induced adipose tissue inflammation and insulin resistance. Our results suggests that irbesartan treatment exerts additive benefits for glucose metabolism in hypertensive patients with mental stress.

St. John's Wort Has Metabolically Favorable Effects on Adipocytes In Vivo.

In addition to serving as a storage site for reserve energy, adipocytes play a critical role in whole-body insulin sensitivity and glucose metabolism. St. John's Wort (SJW) is a botanical supplement widely used as an over-the-counter treatment of depression and a variety of other conditions associated with anxiety and nerve pain. Previous studies in our laboratory demonstrated that SJW inhibits insulin-stimulated glucose uptake and adipocyte differentiation in cultured murine and mature human adipocytes. To investigate the effects of SJW on adipocyte function in vivo, we utilized C57BL/6J mice. In our studies, mice were administered SJW extract (200 mg/kg) once daily by gavage for two weeks. In contrast to our in vitro studies, mice treated with SJW extract showed increased levels of adiponectin in white adipose tissue in a depot specific manner (P < 0.01). SJW also exerted an insulin-sensitizing effect as indicated by a significant increase in insulin-stimulated Akt serine phosphorylation in epididymal white adipose tissue (P < 0.01). Food intake, body weight, fasting blood glucose, and fasting insulin did not differ between the two groups. These results are important as they indicate that SJW does not promote metabolic dysfunction in adipose tissue in vivo.

Effects of Sleeve Gastrectomy on Lipid Metabolism in an Obese Diabetic Rat Model

Laparoscopic sleeve gastrectomy (SG) is a popular bariatric procedure for treating morbid obesity. This study aimed to investigate the relation between SG and lipid metabolism in an obese diabetic rat model. Forty-five male Zucker diabetic fatty (ZDF) rats were divided into three groups: sham-operated (SO) control, gastric banding (GB), and SG. Six weeks after surgery, metabolic parameters, including plasma adiponectin level, small bowel transit, mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPARγ in the liver, skeletal muscle and white adipose tissue, and that of adiponectin in white adipose tissue, and triglyceride (TG) contents in the liver and skeletal muscle were measured. Metabolic parameters in the GB and SG groups were significantly improved compared with those in the SO group. However, plasma total cholesterol (TC) and free fatty acid (FFA) concentrations were significantly lower while the plasma adiponectin level was significantly higher in the SG group than in the GB and SO groups. In addition, small bowel transit time was significantly shorter in the SG group than in the other two groups. Furthermore, in the SG group, mRNA expression of PPARα in the liver and skeletal muscle and that of adiponection and PPARγ in white adipose tissue were significantly higher, while TG in the liver and skeletal muscle were significantly lower, compared with those in the other two groups. These results suggest that SG improves lipid metabolism compared with GB, although there were no significant differences in the effect on weight loss between the two procedures.

Peroxisome Proliferator-Activated Receptors-Alpha and Gamma Are Targets to Treat Offspring from Maternal Diet-Induced Obesity in Mice

AimThe aim of the present study was to evaluate whether activation of peroxisome proliferator-activated receptor (PPAR)alpha and PPARgamma by Bezafibrate (BZ) could attenuate hepatic and white adipose tissue (WAT) abnormalities in male offspring from diet-induced obese dams.Materials and MethodsC57BL/6 female mice were fed a standard chow (SC; 10% lipids) diet or a high-fat (HF; 49% lipids) diet for 8 weeks before mating and during gestation and lactation periods. Male offspring received SC diet at weaning and were subdivided into four groups: SC, SC/BZ, HF and HF/BZ. Treatment with BZ (100 mg/Kg diet) started at 12 weeks of age and was maintained for three weeks.ResultsThe HF diet resulted in an overweight phenotype and an increase in oral glucose intolerance and fasting glucose of dams. The HF offspring showed increased body mass, higher levels of plasmatic and hepatic triglycerides, higher levels of pro-inflammatory and lower levels of anti-inflammatory adipokines, impairment of glucose metabolism, abnormal fat pad mass distribution, higher number of larger adipocytes, hepatic steatosis, higher expression of lipogenic proteins concomitant to decreased expression of PPARalpha and carnitine palmitoyltransferase I (CPT-1) in liver, and diminished expression of PPARgamma and adiponectin in WAT. Treatment with BZ ameliorated the hepatic and WAT abnormalities generated by diet-induced maternal obesity, with improvements observed in the structural, biochemical and molecular characteristics of the animals' livers and epididymal fat.ConclusionDiet-induced maternal obesity lead to alterations in metabolism, hepatic lipotoxicity and adverse liver and WAT remodeling in the offspring. Targeting PPAR with Bezafibrate has beneficial effects reducing the alterations, mainly through reduction of WAT inflammatory state through PPARgamma activation and enhanced hepatic beta-oxidation due to increased PPARalpha/PPARgamma ratio in liver.

Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity

Recruitment of activated immune cells into white adipose tissue (WAT) is linked to the development of insulin resistance and obesity, but the mechanism behind this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells controls inflammation and insulin resistance in obesity. Selective deletion of Y1 receptors in the hematopoietic compartment of mice leads to insulin resistance and inflammation in WAT under high fat–fed conditions. This is accompanied by decreased mRNA expression of the anti-inflammatory marker adiponectin in WAT and an increase of the proinflammatory monocyte chemoattractant protein-1 (MCP-1). In vitro, activated Y1-deficient intraperitoneal macrophages display an increased inflammatory response, with exacerbated secretion of MCP-1 and tumor necrosis factor, whereas addition of neuropeptide Y to wild-type macrophages attenuates the release of these cytokines, this effect being blocked by Y1 but not Y2 receptor antagonism. Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased insulin-induced phosphorylation of the insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1. Thus, Y1 signaling in hematopoietic-derived cells such as macrophages is critical for the control of inflammation and insulin resistance in obesity.

Cilnidipine regulates glucose metabolism and levels of high-molecular adiponectin in diet-induced obese mice

The aim of the present study is to examine the effects of the antihypertensive drug cilnidipine on glucose metabolism and adipocytokines, including adiponectin, in diet-induced obese (DIO) mice. The effects of cilnidipine on insulin sensitivity and the levels of adiponectin in DIO mice were examined after the mice had been treated with cilnidipine dissolved in water at a dose of 0.2 g l(-1) for 14 days. As expected, treatment with cilnidipine decreased the systolic and diastolic blood pressures in DIO mice, compared with control mice (P<0.05 for each parameter). Cilnidipine treatment improved glucose and insulin sensitivity in DIO mice. In addition, cilnidipine treatment dramatically increased the level of adiponectin in white adipose tissue (P<0.05) and the circulating levels of total and high-molecular weight (HMW) adiponectin in DIO mice (P<0.01 for each parameter). Furthermore, the secretion of HMW adiponectin and the ratio of HMW adiponectin/total adiponectin were both increased after cilnidipine treatment. Finally, the secretion of adiponectin from adipocytes was increased after cilnidipine treatment. Taken together, these results indicate that cilnidipine improves insulin tolerance and adiponectin levels, especially high-molecular type adiponectin, in DIO mice.

Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats

Lipoic acid (LA) is an antioxidant with antiobesity and antidiabetic properties. Adiponectin is an adipokine with potent anti-inflammatory and insulin-sensitizing properties. AMP-activated protein kinase (AMPK) is a key enzyme involved in cellular energy homeostasis. Activation of AMPK has been considered as a target to reverse the metabolic abnormalities associated with obesity and type 2 diabetes. The aim of this study was to determine the effects of LA on AMPK phosphorylation and adiponectin production in adipose tissue of low-fat (control diet) and high-fat diet-fed rats. Dietary supplementation with LA reduced body weight and adiposity in control and high-fat-fed rats. LA also reduced basal hyperinsulinemia as well as the homeostasis model assessment (HOMA) levels, an index of insulin resistance, in high-fat-fed rats, which was in part independent of their food intake lowering actions. Furthermore, AMPK phosphorylation was increased in white adipose tissue (WAT) from LA-treated rats as compared with pair-fed animals. Dietary supplementation with LA also upregulated adiponectin gene expression in WAT, while a negative correlation between adiposity-corrected adiponectin levels and HOMA index was found. Our present data suggest that the ability of LA supplementation to prevent insulin resistance in high-fat diet-fed rats might be related in part to the stimulation of AMPK and adiponectin in WAT.

Efecto del tratamiento con candesartan sobre los mecanismos y factores implicados en el desarrollo de la enfermedad cardiovascular asociada a sobrepeso y exceso de tejido adiposo visceral en la rata

Objective The renin angiotensin system has been shown to participate in the development of metabolic syndrome. The aim of this study was to determine whether the angiotensin ii type 1 receptor blocker, candesartan, exerts a protective effect against metabolic and vascular abnormalities in rats fed a high fat diet (HFD). Methods Sprague Dawley rats (n = 30) were divided into three groups: 1) rats fed a standard diet for 7 weeks, used as a control group; 2) rats fed a HFD (33.5% fat) for 7 weeks; and 3) rats fed a HFD (33.5% fat) treated with candesartan (2 mg/kg/day) for 7 weeks. Body weight, white and brown adipose tissue weight, plasma concentrations and protein expression of leptin and adiponectin in white adipose tissue, glucose and lipid metabolism were investigated. Results HFD rats showed increased body, epididymal and lumbar adipose tissue weights. Candesartan attenuated all of these parameters. The leptin/adiponectin ratio of plasma concentrations and protein expression in lumbar adipose tissue increased in HDF rats, and were normalized by candesartan. Candesartan also improved insulin sensitivity and lipid profile. Conclusion Correction of the leptin-adiponectin imbalance may be an important mechanism participating in the protective effect of candesartan in HDF rats.

Exposure to an organometal compound stimulates adipokine and cytokine expression in white adipose tissue

Objective White adipose tissue (WAT) is now considered a defined tissue capable of interactions with other organ systems. WAT role in elevating the level of systemic chronic inflammation suggests that alterations in this tissue as the result of disease or environmental factors may influence the development and progression of various obesity-related pathologies. This study investigated WAT cell-specific responses to an organometal compound, trimethyltin (TMT), to determine possible contribution to induced inflammation. Methods Human primary mature adipocytes and macrophage differentiated THP-1 cells were cultured in TMT presence and relative toxicities and different adipokine levels were determined. The inflammatory response was examined in TMT presence for primary cells from obese ob/ob mice WAT, and after TMT injection in ob/ob mice. Results Both adipocytes and macrophages were resistant to cell death induced by TMT. However, adipocytes cultured in TMT presence showed increased expression of TNFα and IL-6, and modified leptin levels. In macrophage cultures, TMT also increased TNFα and IL-6, while MCP-1 and MIP-1α were decreased. In vivo, a single injection of TMT in ob/ob mice, elevated TNFα, MIP-1α and adiponectin in WAT. Conclusions Elevation of the inflammatory related products can be induced by chemical exposure in adipocytes and macrophages, as well as murine WAT. These data suggest that numerous factors, including a systemic chemical exposure, can induce an inflammatory response from the WAT. Furthermore, when characterizing both chemical-induced toxicity and the progression of the chronic inflammation associated with elevated WAT content, such responses in this target tissue should be taken into consideration.

The protective effect of irbesartan in rats fed a high fat diet is associated with modification of leptin–adiponectin imbalance

It has been shown that the renin-angiotensin system participates in the development of the metabolic syndrome. This study aimed to show whether the angiotensin II type 1 receptor blocker, irbesartan, exerts a protective effect against metabolic and cardiovascular abnormalities in rats fed a high fat diet (HFD). Wistar rats (n = 30) were divided into three groups: (1) rats fed a standard diet for 7 weeks were used as a control group; (2) rats fed a HFD (33.5% fat) for 7 weeks; and (3) rats fed a HFD (33.5% fat) treated with irbesartan (0.1 mg/kg per day) for 7 weeks. Body weight, white and brown adipose tissue weight, plasma concentrations and protein expression of leptin and adiponectin in white adipose tissue, and glucose metabolism were investigated. Vascular reactivity in aortic rings and heart function were also evaluated. HFD rats showed increased (P < 0.05) body, epididymal and lumbar adipose tissue weights, but did not experience a change in brown adipose tissue weight. Irbesartan attenuated (P < 0.05) all of these parameters, but increased brown adipose tissue weight. The leptin/adiponectin ratio of plasma concentrations and protein expression in lumbar adipose tissue increased (P < 0.05) in HFD rats, and were normalized by irbesartan. Along with these changes, irbesartan improved (P < 0.05) insulin sensitivity and exaggerated responses to angiotensin I and II in the aorta. Irbesartan reduced body and white adipose tissue weights, improved glucose metabolism and vascular function in the aorta. The correction of leptin-adiponectin imbalance may be an important mechanism participating in the protective effect of irbesartan in HFD rats.

Abstract 1125: Mulberry Leaf Ameliorates The Production Of Adipocytokines By Inhibiting Oxidative Stress In White Adipose Tissue In db/db Mice

Mulberry leaf (ML) is commonly used to feed silkworms. Previous study showed that ML ameliorates atherosclerosis. However, its mechanism is not completely understood. Because dysregulated production of adipocytokines is involved in the development of the metabolic syndrome and cardiovascular disease, we examined the effect of ML on the production of adipocytokines and metabolic disorders related to the metabolic syndrome, and compared its effect with that of a PPARγ agonist, pioglitazone (Pio). By treating obese diabetic db/db mice with ML, Pio, and their combination, we investigated the mechanism by which they improve metabolic disorders. In this study, db/+m (lean control) and db/db mice were fed a standard diet with or without 3% (w/w) ML and/or 0.01% (w/w) Pio for 12 weeks from 9 weeks of age. At the end of the experiment we found that ML decreased plasma glucose and triglyceride by 32% and 30%, respectively. Interestingly, administration of ML in addition to Pio showed additive effects; further 40% and 30% reduction in glucose and triglyceride compared with Pio treatment, respectively. Moreover, administration of ML in addition to Pio suppressed the body weight increase by Pio treatment and reduced visceral/subcutaneous fat ratio by 20% compared with control db/db mice. Importantly, ML treatment increased expression of adiponectin in white adipose tissue (WAT) by 40%, which was only found in db/db mice, not in control db/+m mice. Combination of ML and Pio increased plasma adiponectin concentrations by 25% and its expression in WAT by 17% compared with Pio alone. In contrast, ML decreased expression of TNF-α and MCP-1 by 25% and 20%, respectively, and the addition of Pio resulted in a further decrease of these cytokines by about 45%. To study the mechanism, we examined the role of oxidative stress. ML decreased the amount of lipid peroxides by 43% and the expression of NADPH oxidase subunits in WAT, which was consistent with the results of TNF-α and MCP-1. Thus our results indicate that ML ameliorates adipocytokine dysregulation by inhibiting oxidative stress in WAT of obese mice, and that ML may have a potential for the treatment of the metabolic syndrome as well as reducing adverse effects of Pio.

Peroxisome Proliferator-Activated Receptor-α,γ-Agonist Improves Insulin Sensitivity and Prevents Loss of Left Ventricular Function in Obese Dyslipidemic Mice

We investigated the effect of a dual peroxisome proliferator-activated receptor (PPAR)alpha,gamma-agonist on atherosclerosis and cardiac function in mice with combined leptin and low-density lipoprotein receptor deficiency (DKO). In these mice, obesity, diabetes, and hyperlipidemia are associated with accelerated atherosclerosis and loss of cardiac function. We treated 12-week-old DKO mice with the PPARalpha,gamma-agonist (S)-3-(4-(2-carbazol-9-yl-ethoxy) phenyl-2-ethoxy-propionic-acid) for 12 weeks. The agonist lowered free fatty acids with 42% and increased insulin sensitivity with 76%. It had no effect on plasma cholesterol and triglycerides. RT-PCR analysis showed that the agonist increased the expression of fatty acid transport protein-4, fatty acid binding protein-4, glucose transporter-4, hormone-sensitive lipase, and adiponectin in white adipose tissue that was associated with the increase in insulin sensitivity. At 24 weeks, the shortening fraction (SF) of placebo DKO mice was 30% lower than that of C57BL6 mice. The PPAR agonist increased PPARgamma but not PPARalpha expression in the heart and prevented loss of left ventricular function. Adiponectin correlated positively with PPARgamma in the heart and with SF. The agonist had no effect on atherosclerosis in the aortic arch of DKO mice. The dual PPARalpha,gamma-agonist improved insulin sensitivity without affecting cholesterol and triglycerides. This was associated with induction of PPARgamma in the heart and prevention of loss of left ventricle function.

Effect of conjugated linoleic acid on gene expression of adiponectin of obese rat fed with high fat diet

To study the effect of conjugated linoleic acid (CLA) on expression of adiponectin in white adipose tissue of obese rats. Male Wistar rats were randomly divided into control group, high-fat group and high fat + CLA group (0.75 g, 1.50 g, 3.00 g per hundred gram diet weight), we observed the effect of CLA on serum insulin and glucose levels of obese rats, and the reverse transcription polymerase chain reaction (RT-PCR) technique was used to measure the expression level of adiponectin and peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA. The serum insulin and glucose levels of obese rats were (11.11 +/- 2.73) microIU/ml, (5.09 +/- 0.66) mmol/L. The supplement of CLA decreased the hyperinsulinemia and hyperglycemia, the serum insulin in CLA group (0.75 g, 1.50 g, 3.00 g per hundred gram diet weight) were (6.99 +/- 1.77) microIU/ml, (7.36 +/- 1.48) microIU/ml, (7.85 +/- 1.60) microIU/ml (P < 0.05), and glucose were (4.28 +/- 0.72) mmol/L, (4.18 +/- 0.55) mmol/L (P < 0.05), (4.06 +/- 0.63) mmol/L (P < 0.05), CLA can increase the expression of adiponectin and PPARgamma in adipose tissue of obese rat. The CLA might improve the insulin resistance of the obese rat and increase the expression of adiponectin mRNA, which might possibly act through activating PPARgamma.