Adiponectin mRNA Research Articles

Abstract 4661: Preventive effects of branched-chain amino acid supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice

Abstract In the present study, the effects of BCAA supplementation on the spontaneous development of hepatic premalignant lesions, foci of cellular alteration, in db/db obese mice were examined. Male db/db mice were given a basal diet containing 3.0% of either BCAA or casein, a nitrogen-content-matched control of BCAA, for 36 weeks. On killing the mice, supplementation with BCAA significantly inhibited the development of foci of cellular alteration when compared with casein supplementation by inhibiting cell proliferation, but inducing apoptosis. BCAA supplementation increased the expression levels of peroxisome proliferator-activated receptor-γ(PPARγ), p21(CIP1) and p27(KIP1) messenger RNA and decreased the levels of c-fos and cyclin D1 mRNA in the liver. BCAA supplementation also reduced both the amount of hepatic triglyceride accumulation and the expression of interleukin (IL)-6, IL-1β, IL-18 and tumor necrosis factor-α mRNA in the liver. Increased macrophage infiltration was inhibited and the expression of IL-6, TNF-α, and monocyte chemoattractant protein-1 mRNA in the white adipose tissue were each decreased by BCAA supplementation. BCAA supplementation also reduced adipocyte size while increasing the expression of PPARα, PPARγand adiponectin mRNA in the white adipose tissue compared with casein supplementation. These findings indicate that BCAA supplementation inhibits the early phase of obesity-related liver tumorigenesis by attenuating chronic inflammation in both the liver and white adipose tissue. BCAA supplementation may be useful in the chemoprevention of liver tumorigenesis in obese individuals. Citation Format: Takayasu Ideta. Preventive effects of branched-chain amino acid supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4661. doi:10.1158/1538-7445.AM2015-4661

Hot water extracts of edible Chrysanthemum morifolium Ramat. exert antidiabetic effects in obese diabetic KK-Ay mice.

In this study, the antidiabetic effects of a hot water extract of edible Chrysanthemum morifolium Ramat. (HW-ECM) were investigated in type 2 diabetic mice. HW-ECM improved blood glucose levels and insulin resistance and increased adiponectin mRNA expression in adipose tissues and protein concentrations in the plasma. Moreover, it increased adipose mRNA and protein expressions of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adiponectin transcription, and mRNA expression of its downstream target genes. It also reduced the adipose cell size and attenuated the mRNA expression of pro-inflammatory adipocytokines in adipose tissues. These data presumably indicate a hypoglycemic mechanism of HW-ECM, involving increased PPARγ expression, decreased the adipocyte sizes, and suppression of chronic inflammation in adipose tissues. Finally, elevated adiponectin levels lead to amelioration of insulin resistance and the corresponding hypoglycemic effects. Therefore, HW-ECM indicates its potential as a functional food for type 2 diabetes.

Coordinated regulation of scopoletin at adipose tissue–liver axis improved alcohol-induced lipid dysmetabolism and inflammation in rats

There is increasing evidence that alcohol-induced white adipose tissue (WAT) dysfunction contributes to disturbance of hepatic lipid metabolism. This study investigated the effects of scopoletin on lipid homeostasis and inflammation at the WAT and liver in chronic alcohol-fed rats. Rats were fed a liquid diet containing 5% alcohol with or without two doses of scopoletin (0.001% and 0.005%) for 8 weeks. Scopoletin decreased serum triglyceride and cytokines (TNFα and IL-6) levels and hepatic and WAT lipid levels, whereas it increased WAT adiponectin mRNA and serum adiponectin levels, up-regulated hepatic gene and protein expression of AdipoR2 and activated AMPK. Additionally, scopoletin inhibited the expression of lipogenic genes (SREBP-1c and Fasn) and increased the expression of fatty acid oxidative genes (PPARα, Acsl1, CPT, Acox, and Acaa1a) in both WAT and liver. Alcohol led to significant up-regulation of WAT lipolysis and hepatic Cidea gene expression, whereas it decreased the WAT Cidea gene level; however, scopoletin reversed these changes. Scopoletin significantly down-regulated TLR4 signaling genes such as MyD88, TRIF, NFκB, TNFα and IL-6 in WAT and liver. These results indicated that coordinated regulation of scopoletin at the WAT–liver axis may play an important role in improvement of alcohol-induced lipid dysregulation and inflammation.

High fat diet induced changes in gastric vagal afferent response to adiponectin

Food intake is regulated by vagal afferent signals from the stomach. Adiponectin, secreted primarily from adipocytes, also has a role in regulating food intake. However, the involvement of vagal afferents in this effect remains to be established. We aimed to determine if adiponectin can modulate gastric vagal afferent (GVA) satiety signals and further whether this is altered in high fat diet (HFD)-induced obesity.Female C57BL/6J mice were fed either a standard laboratory diet (SLD) or a HFD for 12weeks. Plasma adiponectin levels were assayed, and the expression of adiponectin in the gastric mucosa was assessed using real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The location of adiponectin protein within the gastric mucosa was determined by immunohistochemistry. To evaluate the direct effect of adiponectin on vagal afferent endings we determined adiponectin receptor expression in whole nodose ganglia (NDG) and also specifically in GVA neurons using retrograde tracing and qRT-PCR. An in vitro preparation was used to determine the effect of adiponectin on GVA response to mechanical stimulation.HFD mice exhibited an increased body weight and adiposity and showed delayed gastric emptying relative to SLD mice. Plasma adiponectin levels were not significantly different in HFD compared to SLD mice. Adiponectin mRNA was detected in the gastric mucosa of both SLD and HFD mice and presence of protein was confirmed immunohistochemically by the detection of adiponectin immunoreactive cells in the mucosal layer of the stomach. Adiponectin receptor 1 (ADIPOR1) and 2 (ADIPOR2) mRNA was present in both the SLD and HFD whole NDG and also specifically traced gastric mucosal and muscular neurons. There was a reduction in ADIPOR1 mRNA in the mucosal afferents of the HFD mice relative to the SLD mice. In HFD mice adiponectin potentiated gastric mucosal afferent responses to mucosal stroking, an effect not observed in SLD mice. Adiponectin reduced the responses of tension receptors to circular stretch to a similar extent in both SLD and HFD mice.In conclusion, adiponectin modulates GVA satiety signals. This modulatory effect is altered in HFD-induced obesity. It remains to be conclusively determined whether this modulation is involved in the regulation of food intake and what the whole animal phenotypic consequence is.

The association of bone turnover markers with pro- and anti-inflammatory adipokines in patients with gestational diabetes.

The aim of the study was to assess differences in circulating osteocalcin (OC) and osteoprotegerin (OPG), as well as in their expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from patients with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Serum levels of OC, OPG and soluble nuclear factor-kB ligand (sRANKL) were measured in 49 women with GDM and 30 subjects with NGT between weeks 24-32 of gestation, and three months after childbirth. OC and OPG mRNA expression was measured in 23 patients with GDM and 23 women with NGT at term, using quantitative real-time RT-PCR. The patients with GDM had decreased OC mRNA expression in SAT (p=0.015), lower adiponectin mRNA expression in VAT (p=0.039), and a lower circulating adiponectin level (p=0.04). Multiple regression analysis revealed that serum adiponectin was significantly associated with OC mRNA expression in SAT (b=0.49, p=0.03). Three months postpartum, the OPG/sRANKL ratio was markedly higher in the subjects with prior GDM (p=0.03) and correlated positively with HbA1c (R=0.33; p=0.04), fasting insulin (R=0.35; p=0.03) and HOMA-IR (R=0.34; p=0.04). In the patients with GDM decreased OC mRNA expression in SAT might be associated with a reduced stimulatory effect on adiponectin expression in adipose tissue. On the other hand, higher OPG/sRANKL ratio suggests a better protection against bone loss in the subjects with prior GDM.

Adiponectin deletion impairs insulin signaling in insulin-sensitive but not insulin-resistant 3T3-L1 adipocytes.

Previous reports have demonstrated that the adipocyte-derived peptide adiponectin is closely associated with insulin resistance due to its insulin-sensitizing and anti-inflammatory properties in peripheral tissues; however the autocrine effects of adiponectin remain elusive. This study investigated regulatory effects of adiponectin on glucose transport and insulin signaling in insulin-sensitive or insulin-resistant 3T3-L1 adipocytes. 3T3-L1 fibroblasts were transfected with non-target or adiponectin (ADN) siRNA and differentiated. Chronic treatment with insulin (24h, 100 nM) was employed to induce insulin resistance in differentiated adipocytes. Insulin-stimulated glucose transport was measured and protein and mRNA levels were assessed by Western blot and RT-PCR. Prolonged incubation with insulin significantly reduced insulin-stimulated glucose uptake, suggesting the development of insulin resistance and adiponectin mRNA expression. In this insulin-resistant condition, adiponectin deletion did not alter insulin-stimulated glucose uptake. In insulin-sensitive adipocytes, adiponectin ablation reduced insulin-stimulated glucose uptake, expression of IRS-1 and GLUT4, and GLUT4 translocation to the membrane. Adiponectin knockdown did not affect the activation of AKT and p38MAPK (phosphorylation form/total form), but significantly decreased the activation of AMPK in insulin-responsive adipocytes. Adiponectin deficiency suppresses insulin-induced glucose uptake, insulin signaling, and the AMPK pathway only in insulin-responsive 3T3-L1 adipocytes.

Comprehensive molecular characterization of human adipocytes reveals a transient brown phenotype.

BackgroundFunctional brown adipose tissue (BAT), involved in energy expenditure, has recently been detected in substantial amounts in adults. Formerly overlooked BAT has now become an attractive anti-obesity target.Methods and resultsMolecular characterization of human brown and white adipocytes, using a myriad of techniques including high-throughput RNA sequencing and functional assays, showed that PAZ6 and SW872 cells exhibit classical molecular and phenotypic markers of brown and white adipocytes, respectively. However, the pre-adipocyte cell line SGBS presents a versatile phenotype. A transit expression of classical brown markers such as UCP1 and PPARγ peaked and declined at day 28 post-differentiation initiation. Conversely, white adipocyte markers, including Tcf21, showed reciprocal behavior. Interestingly, leptin levels peaked at day 28 whereas the highest adiponectin mRNA levels were detected at day 14 of differentiation. Phenotypic analysis of the abundance and shape of lipid droplets were consistent with the molecular patterns. Accordingly, the oxidative capacity of SGBS adipocytes peaked on differentiation day 14 and declined progressively towards differentiation day 28.ConclusionsOur studies have unveiled a new phenotype of human adipocytes, providing a tool to identify molecular gene expression patterns and pathways involved in the conversion between white and brown adipocytes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0480-6) contains supplementary material, which is available to authorized users.

Three-dimensional spheroid cell model of in vitro adipocyte inflammation.

To improve treatment of obesity, a contributing factor to multiple systemic and metabolic diseases, a better understanding of metabolic state and environmental stress at the cellular level is essential. This work presents development of a three-dimensional (3D) in vitro model of adipose tissue displaying induced lipid accumulation as a function of fatty acid supplementation that, subsequently, investigates cellular responses to a pro-inflammatory stimulus, thereby recapitulating key stages of obesity progression. Three-dimensional spheroid organization of adipose cells was induced by culturing 3T3-L1 mouse preadipocytes on an elastin-like polypeptide-polyethyleneimine (ELP-PEI)-coated surface. Results indicate a more differentiated phenotype in 3D spheroid cultures relative to two-dimensional (2D) monolayer analogues based on triglyceride accumulation, CD36 and CD40 protein expression, and peroxisome proliferator-activated receptor-γ (PPAR-γ) and adiponectin mRNA expression. The 3T3-L1 adipocyte spheroid model was then used to test the effects of a pro-inflammatory microenvironment, namely maturation in the presence of elevated fatty acid levels followed by acute exposure to tumor necrosis factor alpha (TNF-α). Under these conditions, we demonstrate that metabolic function was reduced across all cultures exposed to TNF-α, especially so when pre-exposed to linoleic acid. Further, in response to TNF-α, enhanced lipolysis, monitored as increased extracellular glycerol and fatty acids levels, was observed in adipocytes cultured in the presence of exogenous fatty acids. Taken together, our 3D spheroid model showed enhanced adipogenic differentiation and presents a platform for elucidating the key phenotypic responses that occur in pro-inflammatory microenvironments that characterize obesogenic states.

Hikiamides A-C, Cyclic Pentadepsipeptides from Fusarium sp. TAMA 456.

Three new cyclic pentadepsipeptides, hikiamides A-C (1-3), were isolated from the culture extract of Fusarium sp. TAMA 456. The structures were determined by spectroscopic analysis using NMR and MS, and the absolute configurations were established by using Marfey's method and chiral HPLC analysis. Hikiamides induced the differentiation of murine ST-13 preadipocytes into mature adipocytes at 2 μM and adiponectin mRNA expression (5- to 13-fold higher than control). They also induced PPAR-γ-dependent gene expression at a concentration from 0.63 to 10 μM in a gene reporter assay.

0415 : CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice

Lymphocytes play a critical role in visceral adipose tissue inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Treg) compartment; however its role during obesity is unknown. During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knock-out mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions. Cd28 deficiency decreased pathogenic T-cells and Treg content within adipose tissue without changing macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzymes mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number T-cells in epididymal adipose tissue but not inflammatory cytokines levels and failed to improve liver fat accumulation. Deletion of CD28 creates a new pro/anti-inflammatory balance in epididymal adipose tissue and liver and exerts a protective effect against hepatic steatosis.

CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice.

Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown. During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions. Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation. Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis.

Correlation between type 2 diabetes and DNA methylation and mRNA expression of APN in abdominal adipose tissues in Xinjiang Uygur population

To investigate the relationship between type 2 diabetes mellitus (T2DM) onset and development and mRNA expression and promoter methylation of adiponectin (APN) gene in abdominal adipose tissues of Xinjiang Uygur population, abdominal adipose tissues of omentum were collected and divided into control, obesity and T2DM groups. The status of APN promoter methylation was detected by denaturing high performance liquid chromatography (DHPLC), while the mRNA expression level of APN was detected by RT-PCR. Results show that methylation positive rate of APN was at the lowest level in control, middel in obesity and highest in T2DM groups, and the differences are statistically significant. Comparing the APN mRNA relative copy number of adipose tissue in each group, we found that the relative copy number of APN in control group is significantly higher than that of obesity and T2DM groups. There is a negative correlation between the mRNA expression level of APN in abdominal adipose tissue and fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and triglyceride (TG) level. There is a negative correlation in DNA promoter methylation and mRNA expression of APN gene. Relative copy number of APN in DNA methylation positive group is significantly lower than that of the negative group. In conclusion, increased APN promoter methylation results in decreased mRNA expression, which induces glucose and lipid metabolic disorder, thus contributing to the initiation and development of T2DM in Xinjiang Uygur population.

Olive Leaf Extract Elevates Hepatic PPAR α mRNA Expression and Improves Serum Lipid Profiles in Ovariectomized Rats.

We hypothesized that olive leaf extract might alleviate dyslipidemia resulting from estrogen deficiency. Serum lipid profile and mRNA expression of the related genes in the liver and adipose tissue were analyzed after providing olive leaf extract (200 or 400 mg/kg body weight; n=7 for each group) to ovariectomized rats for 10 weeks. After 10 weeks' administration, the rats in the olive leaf extract-administered groups showed significantly lower levels of serum triglyceride and very-low-density lipoprotein (VLDL)-cholesterol compared with the rats in the control group, whereas the administration of olive leaf extract did not significantly change the elevated low-density lipoprotein cholesterol levels. In addition, administration of high dose of olive leaf extract significantly decreased the liver triglyceride and increased serum estradiol levels. mRNA expressions of peroxisome proliferator-activated receptor alpha (PPAR α) and acyl-CoA oxidase (ACO) were not affected by ovariectomy, however, administration of olive leaf extract significantly increased both PPAR α and ACO mRNA expression. Expression of adiponectin mRNA in adipose tissue was significantly decreased in the ovariectomized control group. Rats administered low-dose olive leaf extract showed significantly elevated adiponectin mRNA expression compared with rats in the ovariectomized control group. Even though dose-dependent effects were not observed in most of the measurements, these results suggest that genes involved in lipid metabolism may be regulated by olive leaf extract administration in ovariectomized rats.

Dietary açai attenuates hepatic steatosis via adiponectin-mediated effects on lipid metabolism in high-fat diet mice

Polyphenols, especially anthocyanins, have been considered promising for the prevention of nonalcoholic fatty liver disease (NAFLD). This study investigated whether açai (Euterpe oleracea Mart.), a source of anthocyanins and recognized as one of the new “superfruits”, could alleviate high-fat diet (HFD)-induced NAFLD in mice. In HFD mice, aqueous açai extract (AAE) administration (3 g/kg) for six weeks improved insulin resistance index and increased adiponectin mRNA expression in adipose tissue and serum levels. Furthermore, AAE decreased the total liver triacylglycerol content and attenuated HFD-induced hepatic steatosis. This reduced hepatic lipid content was associated with AAE-mediated up-regulation of genes involved in adiponectin signaling, including adiponectin receptor 2, PPAR-α, and its target gene, carnitine palmitoyltransferase. Thus, dietary açai can protect liver from steatosis through its enhancement of adiponectin levels, improvement of insulin sensitivity, and increase in PPAR-α-mediated fatty acid oxidation.

Lycopene-rich tomato oleoresin modulates plasma adiponectin concentration and mRNA levels of adiponectin, SIRT1, and FoxO1 in adipose tissue of obese rats.

To investigate whether lycopene can modulate adiponectin levels and SIRT1 and FoxO1 gene expression in the adipose tissue of diet-induced obese rats. Male Wistar rats were first fed with hypercaloric diet (HD, n = 12) for 6 weeks, and afterward, these rats were randomly assigned to receive HD (n = 6) or HD with lycopene-rich tomato oleoresin (equivalent to lycopene 10 mg/kg body weight (BW)/day, HD + L, n = 6) by gavage for additional 6 weeks. Plasma lycopene and adiponectin levels were analyzed by high-performance liquid chromatography and immunoassay, respectively. The messenger RNA (mRNA) expressions of adiponectin, Sirtuin 1 (SIRT1), Forkhead box O 1 (FoxO1), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and PPARγ in adipose tissues were determined by quantitative polymerase chain reaction. Lycopene was detected in the plasma of rats in HD + L group but not in the HD group. Although both BW and adiposity were not different between the two groups, there was a significant increase in both plasma concentration and mRNA expression of adiponectin in the adipose tissue of the HD + L group. In addition, the lycopene supplementation upregulated mRNA expressions of SIRT1, FoxO1, and FAT/CD36 but downregulated PPARγ in adipose tissue of obese rats. These data suggest that lycopene, in the concentration used, is not toxic and also its health benefits in adipose tissue may play a role against obesity-related complications.

Characterisation of adiponectin and its receptors in the bovine mammary gland and in milk

Adiponectin is an adipocyte-derived hormone, which circulates in the form of homo-multimers. The individual oligomers have a distinct profile of activity, playing crucial roles in several biological processes, including metabolism and inflammation. Adiponectin exerts many of its effects by interacting with the receptors, AdipoR1 and AdipoR2. In the present study, mRNA expression of adiponectin, AdipoR1 and AdipoR2 was evaluated by quantitative PCR in different areas of the mammary gland in healthy lactating cows. The adiponectin isoforms in milk and blood were investigated by Western blotting and 2D-electrophoresis, and the presence of adiponectin protein was determined by immunohistochemistry.Low level expression of adiponectin mRNA was found in all areas of bovine mammary gland tissues examined. AdipoR1 and AdipoR2 mRNAs were also detected in mammary tissues and their expression was particularly prominent in the parenchyma and cistern. Western blotting revealed a heterogeneous electrophoretic pattern, indicating that different adiponectin isoforms exist in milk, compared with blood. In particular, milk shows a low molecular weight isoform of adiponectin, corresponding to the globular domain. Adiponectin in milk is characterised by a more complex 2D electrophoretic pattern, compared with blood, as illustrated by the presence of proteins of different molecular weights and isoelectric points. Adiponectin protein was detected by immunohistochemistry in epithelial cells lining the secretory alveoli, in secretum within the alveolar lumen and in small peripheral nerves. The study findings support a role for adiponectin in regulating metabolism and immunity of the bovine mammary gland and potentially the calf intestine, following ingestion of milk.

Vaspin promotes 3T3-L1 preadipocyte differentiation

Vaspin, a novel adipocyte factor secreted from visceral adipose tissues, is associated with obesity and insulin resistance and can regulate glucose and lipid metabolism, increase insulin sensitivity, and suppress inflammation; however, the underlying mechanisms remain unknown. Proliferation and maladaptive differentiation are important pathological mechanisms underlying obesity. This study aimed to evaluate the effects of vaspin on the proliferation and differentiation of preadipocyte 3T3-L1 cells and to explore the likely mechanisms responsible for 3T3-L1 differentiation. Vaspin was added to cultured 3T3-L1 cells, and the differentiation of adipocytes was evaluated using Oil Red O staining. The AKT signaling pathway and specific differentiation factors related to the differentiation of preadipocyte 3T3-L1 cells, peroxisome proliferator-activated γ and the CCAAT/enhancer-binding protein (C/EBP) family, were evaluated using reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses during the early phase of differentiation. Additionally, adiponectin mRNA, interleukin-6 mRNA (IL-6 mRNA), and glucose transporter-4 (GLUT4) protein levels were measured in the differentiated adipocytes. The results indicated that vaspin promotes the intracellular accumulation of lipids and increases differentiation-related factors, including peroxisome proliferator-activated receptor γ, C/EBPα, and free fatty acid-binding protein 4 (FABP4), in a dose-dependent manner. Additionally, vaspin (200 ng/mL) increased the mRNA and protein levels of C/EBPβ, peroxisome proliferator-activated γ, C/EBPα, and FABP4. Moreover, compared with the control, significantly smaller eight-day differentiated adipocytes were observed, and these cells exhibited decreased IL-6 mRNA and increased GLUT4 mRNA levels; these results also indicated the potential of vaspin to promote the insulin-mediated AKT signaling pathway during the early phase of differentiation. In conclusion, vaspin is able to promote the differentiation of 3T3-L1 preadipocytes and may increase their sensitivity to insulin and suppress obesity.

Fetal life malnutrition is not reflected in the relative abundance of adiponectin and leptin mRNA in adipose tissue in male mink kits at 9.5 weeks of age

Malnutrition in fetal life and during suckling have in some animal studies resulted in adaptive changes related to the fat and glucose metabolism, which in the long term might predispose the offspring for metabolic disorders such as obesity later in life. The objective was to study the effect of fetal life malnutrition in male mink on the gene expression of leptin and adiponectin in different adipose tissue sites. Thirty-two male mink, strict carnivore species, exposed to low (FL) or adequate (FA) protein provision the last 16.3 ± 1.8 days of fetal life and randomly assigned to a low (LP) or adequate (AP) protein diet from 7 to 9.5 weeks of age were used. Adipose tissues (subcutaneous, perirenal and mesenteric) were analyzed using qPCR. Fetal life or post-weaning protein provision did not affect the relative abundances of leptin and adiponectin mRNAs in adipose tissue at 9.5 weeks of age. Relative abundances of leptin and adiponectin mRNAs were different between adipose tissue sites and were significantly higher in subcutaneous than in perirenal and mesenteric tissues. Fetal life protein malnutrition in male mink, did not result in adaptive changes in the gene expression of leptin and adiponectin mRNAs in adipose tissue at 9.5 weeks of age as found in rodents. However, both leptin and adiponectin mRNAs were significantly differently expressed between tissue sites.

Anti-hypertensive azelnidipine preserves insulin signaling and glucose uptake against oxidative stress in 3T3-L1 adipocytes

It is known that reactive oxygen species (ROS) are involved in the development of insulin resistance as well as pancreatic β-cell dysfunction both of which are often observed in type 2 diabetes. In this study, we evaluated the effects of azelnidipine, a calcium channel blocker, on ROS-mediated insulin resistance in adipocytes. When 3T3-L1 adipocytes were exposed to ROS, insulin-mediated glucose uptake was suppressed, but such phenomena were not observed in the presence of azelnidipine. Phosphorylation of insulin receptor and phosphorylation of Akt were suppressed by ROS, which was mitigated by azelnidipine treatment. Activation of the JNK pathway induced by ROS was also reduced by azelnidipine. Various inflammatory cytokine levels were increased by ROS, which was also suppressed by azelnidipine treatment. In contrast, adiponectin mRNA and secreted adiponectin levels were reduced by ROS, which was refilled by azelnidipine treatment. In conclusion, azelnidipine preserves insulin signaling and glucose uptake against oxidative stress in 3T3-L1 adipocytes.

Leptin and adiponectin mRNA expression from the adipose tissue surrounding the adrenal neoplasia.

Interplay between adipose tissue and adrenal glands has been recently suggested, without well-founded actions of locally adipose tissue surrounding the adrenal glands. We hypothesized that the local expression of leptin and adiponectin can be associated with pathological changes of the adrenal glands. We evaluated RT-PCR of leptin and adiponectin mRNA expression from the adipose tissue surrounding adrenal glands in 30 patients, collecting adipose tissue surrounding the adrenal neoplasms, peri-renal and subcutaneous depots. Leptin mRNA levels from adrenal neoplasia and peri-renal fat were significantly higher in aldosterone-producing adenoma than in nonfunctioning adenomas (P < 0.001 and P < 0.02, respectively). In patients with Cushing's syndrome leptin mRNA levels were significantly higher in adrenal fat than in peri-renal (P < 0.05) and subcutaneous adipose tissue (P < 0.001). Adiponectin mRNA expression from adrenal neoplasia was significantly lower than that from peri-renal and subcutaneous fat depots (P < 0.05). Leptin and adiponectin plasma levels significantly correlated with their mRNA expression from the fat depot surrounding the adrenal neoplasia. Our findings suggest an active role of the fat depot surrounding the adrenal neoplasia, with local secretion of leptin and adiponectin.