12α-Hydroxylated bile acid enhances accumulation of adiponectin and immunoglobulin A in the rat ileum

We previously reported that dietary supplementation with cholic acid (CA), the primary 12α-hydroxylated (12αOH) bile acid (BA), reduces plasma adiponectin concentration in rats. The aim of this study was to examine the distribution of adiponectin in the body of CA-fed rats and its influence on mucosal immunoglobulin A concentration in the intestine. Rats were fed a diet supplemented with or without CA (0.5 g CA/kg diet) for 13 weeks. A reduction in plasma adiponectin level was observed from week 3. At the end of the experiment, the CA diet reduced plasma adiponectin concentration both in the portal and aortic plasma. Accumulation of adiponectin was accompanied by an increase in cadherin-13 mRNA expression in the ileal mucosa of CA-fed rats. No increase was observed in adiponectin mRNA expression in the ileal and adipose tissues of the CA-fed rats. Immunoglobulin A concentration in the ileal mucosa was elevated in the CA-fed rats and was correlated with the ileal adiponectin concentration. 12αOH BAs may modulate mucosal immune response that are involved in the accumulation of adiponectin in the ileum.

Adropin Slightly Modulates Lipolysis, Lipogenesis and Expression of Adipokines but Not Glucose Uptake in Rodent Adipocytes

Adropin is a peptide hormone which modulates energy homeostasis and metabolism. In animals with diet-induced obesity, adropin attenuates adiposity and improves lipid and glucose homeostasis. Adropin promotes the proliferation of rodent white preadipocytes and suppresses their differentiation into adipocytes. By contrast, the effects of adropin on mature white adipocytes are unknown. Therefore, we aimed to evaluate the effects of adropin on lipolysis, lipogenesis and glucose uptake in white rodent adipocytes. We assessed the effects of adropin on the mRNA expression of adiponectin, resistin and visfatin. White preadipocytes were isolated from male Wistar rats. Differentiated 3T3-L1 cells were used as a surrogate model of white adipocytes. Lipolysis was measured by the evaluation of glycerol and free fatty acid secretion using colorimetric kits. The effects of adropin on lipogenesis and glucose uptake were measured using radioactive-labelled glucose. The expression of adipokine mRNA was studied using real-time PCR. Our results show that adropin slightly promotes lipolysis in rat adipocytes and 3T3-L1 cells. Adropin suppresses lipogenesis in rat adipocytes without influencing glucose uptake. In addition, adropin stimulates adiponectin mRNA expression and suppresses the expression of resistin and visfatin. These results indicate that adropin may be involved in controlling lipid metabolism and adipokine expression in white rodent adipocytes.

Adiponectin and its receptors in patients with cardiovascular disease

Funding Acknowledgements Type of funding sources: None. Aim to determine the features of adiponectin expression, secretion of adiponectin and its receptors in local fat depots in CVD. Materials and methods The study included 90 patients with СAD (Group 1) and 60 patients with heart defects (Group 2). Adipocytes were isolated from samples of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) adipose tissue obtained during CABG or heart valve replacement. The expression of adiponectin was determined by qPCR using TaqManTM Gene Expression Assays (Applied Biosystems, USA) in the ViiA 7 Real-Time PCR System (Applied Biosystems, USA), the levels of expression products was determined using enzyme immunoassay (Bender MedSystems GmbH, Vienna, Austria). The data were analyzed using the statistical software Statistica 9.0. Results EAT adipocytes were characterized by the lowest adiponectin expression relative to adipocytes of other localization both in Group 1 and Group 2. In patients Group 1 adiponectin expression in EAT was reduced relative in SAT and PVAT (by 1.2 and 1.5 times). In Group 2, the adiponectin mRNA in the EAT was lower than in the SAT and PVAT (1.4 and 1.5 times). The expression of adiponectin in EAT in Group 2 exceeded the same indicator in Group 1 by 1.2 times. The maximum expression of adiponectin was observed in the PVAT culture in patients of both groups. For Group 2, this indicator exceeded the values of Group 1 by 1.2 times. The content of adiponectin in the culture EAT was lower than in the SAT, both in Group 1 and Group 2 (by 1.3 and 1.13 times). The level of this indicator in Group 2 was 1.4 times higher than in Group 1. PVAT adipocytes of patients with CAD were characterized by the lowest level of adiponectin secretion in comparison with adipocytes of other localization. The adiponectin level in the PVAT of Group 2 exceeded that of fat stores of other localization and in Group 1 patients by 1.8 times. There were no statistically significant differences in the expression and concentration of adiponectin in the culture of adipocytes of the SAT between the groups of patients. In Group 1, the lowest level of AdipoR1 was found in the adipocyte culture of the PVAT. Noteworthy is the decrease in the level of AdipoR1 in Group 1 compared to the level of Group 2, observed in the SAT and PVAT: 1.3 and 1.5 times. There were no significant differences in the concentration of the AdipoR1 in the EAT, as well as AdipoR2 in all types of AT between the groups of patients. Conclusion: in CVD the EAT is characterized by minimal expression and secretion of adiponectin, regardless of nosology. In CAD despite the high level of expression of adiponectin, the adipocytes of the PVAT were found to have the lowest content in comparison with adipocytes of other localization. Dysregulation of the adiponectin/AdipoR axis is observed in PVAT, which may be due to low expression of adiponectin receptors and long-term processes of its post-translational modification and oligomerization in CAD.

Adipose Tissue Transplant Impregnated with Collagen Increases Engraftment by Promoting Cell Proliferation, Neovascularization, and Macrophage Activity in a Rat

Objectives: To clarify the effect of impregnating transplanted adipose tissue with collagen on angiogenesis, cell proliferation, and tissue remodeling process and to reveal whether collagen impregnation contributes to improving the engraftment of transplanted adipose tissue in rats.Methods: Adipose tissue was harvested from the inguinal and injected into the back of the rat, in addition to collagen. Engraftment tissue was harvested, semi-quantitatively evaluated and underwent HE or Perilipin staining. Moreover, we evaluated viable adipocyte counts and neovascularization. Macrophages were evaluated using flow cytometry, and the adiponectin or VEGF mRNA was detected using real-time PCR. Results: By impregnating transplanted adipose tissue with collagen, higher engraftment rate semi-quantitatively and a greater number of new blood vessels histologically were identified. Perilipin staining revealed a higher adipocyte number. The total cell, M1 macrophage, and M2 macrophage count were higher. There was increased adiponectin mRNA significantly at week 4 compared to that at week 1 after transplantation. Note that the expression levels of VEGF mRNA increased.Discussion: In rats, collagen impregnation enhanced cell proliferation, induced M2 macrophages, which are involved in wound healing, and promoted adipocytes and neovascularization. Therefore, impregnating transplanted adipose tissue with collagen could increase the engraftment rate of adipose tissue.

Expression of adiponectin and il-6 by local fat depots of the heart: relationship with the main risk factors for cardiovascular diseases

Introduction Previous studies have identified a number of pro-inflammatory and other markers potentially associated with atherogenesis, which are also expressed and produced by adipose tissue. Atherosclerosis is a multifactorial disease, in the development of which both unmodifiable factors (gender, age) and modifiable factors (smoking, dyslipidemia) contribute, and further study of the pathogenetic relationships of adipocytokines and CVD risk factors is necessary. Purpose To evaluate the features of the expression of adiponectin and IL-6 in the epicardial (EAT), perivascular (PVAT), subcutaneous adipose tissue (SAT) and its relationship with the main risk factors for CVD. Materials and methods The study included 84 patients with stable coronary artery disease (CAD) who were planning coronary artery bypass grafting (CABG). During the operation, adipose tissue (AT) biopsy samples were obtained. The expression of adiponectin and IL-6 genes was evaluated by the method of quantitative polymerase reaction in real time (PCR) depending on the presence or absence of CVD risk factors. Results It was found that adipocytes of EAT are characterized by the lowest expression of the adiponectin gene against the background of the maximum - IL-6. In men, the adiponectin mRNA level in EAT and PVAT is reduced (2.5 and 2.8 times). The expression of IL-6 in male patients is higher in SAT (3 times) and lower in PVAT than in women. The presence of dyslipidemia is associated with a decrease in the expression of both adiponectin in EAT and PVAT (2.7 and 3.6 times), and IL-6 in PVAT (2.3 times). People with arterial hypertension (AH) have lower levels of adiponectin in EAT and PVAT (2 and 1.8 times) with high levels of IL-6 in SAT and EAT (8 and 10.4 times). With an increase in the experience of hypertension for more than 20 years, adiponectin expression decreases in all types of AT with an increase in IL-6 in PVAT (2 times) and a decrease in SAT. Smoking is associated with increased adiponectin mRNA levels. Patients 51–59 years old are characterized by high expression of IL-6 in EAT and PVAT in comparison with parameters of other age groups. Conclusions The revealed decrease in the expression of adiponectin in EAT against the background of an increase in pro-inflammatory IL-6 can enhance atherogenesis, and in combination with risk factors such as male sex, the presence of dyslipidemia and hypertension contribute to the progression of coronary artery disease. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Russian Scientific Foundation no. 17-75-20026

Relationships between placental adiponectin, leptin, visfatin and resistin and birthweight in cattle

Adipokines can affect intrauterine development while calf birthweight (CBW) is a breeding standard of calves, which reflects the status of fetal intrauterine development. To explore the correlation between placental adipokines and CBW, 54 healthy Chinese Holstein cows were used in the present study. The cows were grouped according to the CBW of their calves. Placentas were collected immediately after delivery and enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction were used to detect the placental expression levels of adiponectin, leptin, visfatin and resistin. Our results show that the mRNA transcription and blood placental content of adiponectin, leptin, visfatin and resistin increased with increasing CBW. The analysis showed that the mRNA transcription levels of placental adiponectin, leptin and resistin were positively correlated with CBW. The mRNA and protein expression levels of adiponectin, leptin and visfatin between the three groups were significantly correlated. Placental resistin mRNA levels correlated positively with adiponectin mRNA, but not leptin or visfatin. The protein expression levels of resistin were significantly positively correlated with those of adiponectin, leptin and visfatin. These results suggest that placental adipokines play important roles in regulating calf intrauterine growth.

Effects of postweaning calorie restriction on accelerated growth and adiponectin in nutritionally programmed microswine offspring

Poor prenatal development, followed by rapid childhood growth, conveys greater cardiometabolic risk in later life. Microswine offspring exposed to perinatal maternal protein restriction [MPR; “low protein offspring” (LPO)] grow poorly in late-fetal/neonatal stages. After weaning to an ad libitum (AL) diet, LPO-AL exhibit accelerated growth and fat deposition rates with low adiponectin mRNA, despite low-normal body fat and small intra-abdominal adipocytes. We examined effects of caloric restriction (CR) on growth and metabolic status in LPO and normal protein offspring (NPO) randomized to AL or CR diets from weaning. CR transiently reduced growth in both LPO and NPO, delaying recovery in female LPO-CR. Over 7.5–12.5 weeks, linear growth rates in LPO-CR were slower than LPO-AL ( P < 0.001) but exceeded NPO-AL; body weight growth rates fell but were lower in LPO-CR versus NPO-CR. Linear acceleration ceased after 12 weeks. At 16 weeks, percent catch-up in LPO-CR was reduced versus LPO-AL ( P < 0.001). Plasma growth hormone was low in LPO ( P < 0.02). CR normalized fat deposition rate, yet adiponectin mRNA remained low in LPO-CR ( P < 0.001); plasma adiponectin was low in all LPO-AL and in female LPO-CR. Insulin sensitivity improved during CR. We conclude that in LPO: 1) CR delays onset of, but does not abolish, accelerated linear growth, despite low growth hormone; 2) CR yields stunting via delayed onset, plus a finite window for linear growth acceleration; 3) MPR lowers adiponectin mRNA independently of growth, adiposity, or adipocyte size; and 4) MPR reduces circulating adiponectin in LPO-AL and female LPO-CR, potentially enhancing cardiometabolic risk.

5,4′-Dihydroxy-7,8-dimethoxyflavanone and Aliarin from Dodonaea viscosa Are Activators of PPARγ

PPARγ agonists are widely used medications in diabetes mellitus therapy. Their role in improving adipose tissue function contributes to antidiabetic effects. The extracts of Dodonaea viscosa have been reported to exert antidiabetic activity. However, the effective mediators and the underlying mechanisms were largely unknown. In this study, we investigated the action on PPARγ transactivation and adipocyte modulation of two typical flavonoid constituents from D. viscosa, 5,4′-dihydroxy-7,8-dimethoxyflavanone and aliarin. Our results showed that 5,4′-dihydroxy-7,8-dimethoxyflavanone and aliarin were potential partial PPARγ agonists. The compounds induced adipogenesis in 3T3-L1 cells, with an upregulated adiponectin mRNA level and enhanced insulin sensitivity. The favorable effects of 5,4′-dihydroxy-7,8-dimethoxyflavanone, aliarin, and other flavonoid constituents on adipocytes might contribute to the antidiabetic efficacy of D. viscosa.