Intracerebroventricular administration of adiponectin attenuates streptozotocin-induced memory impairment in rats.

Alzheimer's disease (AD) has been reported to be linked with diabetes mellitus and insulin resistance. Adiponectin (ADN), an adipocytokine secreted from adipose tissue, is involved in the regulation of insulin sensitivity, energy homeostasis, and mitochondrial dysfunction. In this study, we examined the effect of ADN on passive avoidance memory in animal model of sporadic AD (sAD). On days 1 and 3 after cannulation, rats received intracerebroventricular (icv) injection of streptozotocin (STZ) (3 mg/kg). Thirty minutes before the learning process, animals received saline or ADN in different doses (6, 60, and 600 µg). The step-through latency (STL) and total time spent in the dark compartment (TDC) were recorded and analyzed. In STZ-treated rats, STL was significantly decreased, whereas TDC showed a dramatic increase. In ADN-treated rats, STL was significantly increased (P < 0.01) in all treatment doses. The number of entries was decreased in all applied doses; however, TDC was reduced only by the application of 6 ng of ADN (P < 0.05). It can be concluded that ADN is useful to improve the STZ-induced memory impairment. This study showed, for the first time, that icv administration of ADN could improve the memory acquisition in animal model of sAD.

Differential effects of adiponectin in osteoblast-like cells.

The skeleton should maintain an adequate volume, vigour and strength to carry out the role for which it is designed: to hold the whole soft tissue mass that shapes the body and to protect the vital organs. To fulfil this task a satisfactory food intake is required and regulators that are released in the feeding and fasting states, among other signals indicate how much soft mass needs to be built up. Those signals include the secretion of adipocytokines which could represent a relevant link between soft mass (adipose tissue) and skeleton. We studied the presence of adiponectin receptors (AdipoR1, AdipoR2) and its direct effects in osteosarcoma cell line Saos-2. The results indicated that adiponectin receptors were present in the osteoblastic cells with a higher expression of AdipoR1. Human recombinant globular adiponectin was able to increase viability levels and decrease cytotoxicity rates in cell cultures. Also, adiponectin significantly inhibited alkaline phosphatase activity in supernatants. Osteoprotegerin mRNA expression was significantly reduced after 72 h treatment. The FOS induction was studied and the results exhibited a significant increase caused by adiponectin. In conclusion, all these observations suggest that adiponectin influences bone metabolism decreasing the levels of bone formation. Regulators of adiponectin or its receptors could be circulating to modulate the activities of this peptide.

Effect of the diet components on adiponectin levels / Efecto de los componentes de la dieta sobre los niveles de adiponectina

The prevalence of obesity has reached epidemic proportions worldwide, which requires nutritional interventions for its effective control. Adiponectin has antiinflammatory capacity, improves glucose tolerance and presents decreased plasma expression and concentration in obese individuals. Studies with animals reveal improvement in insulin resistance after the infusion of adiponectin; in humans, caloric restriction increases its levels. The present study aimed to analyze the effects of dietary components on gene expression and plasma concentration of adiponectin. Sixteen articles were found following a literature review —seven with interventions in animal models and nine in human. The results in animal models demonstrate that the consumption of hyperlipidemic diets, rich in saturated fat, reduces the levels of adiponectin, while the diets rich in polyunsaturatedfatty acids and supplementation with omega-3 and eicosapentaenoic acid increase its gene expression and plasma levels. In humans, the consumption of a healthy and Mediterranean diet are positively associated with adiponectin levels, although the mechanisms are not fully understood. Due to the importance of adiponectin in preventingmetabolic diseases and reducing cardiovascular risk, more research are needed on food strategies to promote the increase of adiponectin levels. Therefore, studies must be carried out to evaluate the response to differents ources and levels of various dietary components and the safety of the supplementation of specific nutrients (AU)

La adiponectina tiene capacidad anti-inflamatoria, mejora la tolerancia a la glucosa y presenta una menor expresión de plasma y la concentración en personas obesas. Estudios con animales revelan una mejora en la resistencia a la insulina después de la infusión de la adiponectina, en los seres humanos, el aumento de la restricción calórica ocasiona el aumento os niveles de la adiponectina. El presente estudio tuvo como objetivo analizar los efectos de los componentes de la dieta sobre la expresión génica y la concentración plasmática de la adiponectina. Dieciséis artículos fueron encontrados —siete en modelos animales y nueve en los seres humanos. Los resultados en modelos animales demuestran que el alto consumo de dietas hiperlipidemia, ricos en grasas saturadas, reduce los niveles de adiponectina, mientras que las dietas ricas en ácidos grasos poliinsaturados y la suplementación con omega-3 y ácido eicosapentanoico aumentar su expresión genética y los niveles plasmáticos. En los seres humanos, el consumo de una dieta sana y la dietamediterránea se asocia positivamente con los niveles de adiponectina, aunque los mecanismos no se entienden completamente. Debido a la importancia de la adiponectina en la prevención de las enfermedades metabólicas y la reducción de riesgo cardiovascular, más investigaciones son necesarias sobre las estrategias alimentarias para promover el aumento de los niveles de adiponectina. Por lo tanto, los estudios deben llevarse a cabo para evaluar la respuesta a las diferentes fuentes y los niveles de varios componentes de la dieta y la seguridad de la suplementación de nutrientes específicos (AU)

Systemic fate of the adipocyte-derived factor adiponectin.

OBJECTIVE: The adipocyte-derived secretory protein adiponectin has been widely studied and shown to have potent insulin-sensitizing, antiapoptotic, and anti-inflammatory properties. While its biosynthesis is well understood, its fate, once in circulation, is less well established. RESEARCH DESIGN AND METHODS: Here, we examine the half-life of adiponectin in circulation by tracking fluorescently labeled recombinant adiponectin in the circulation, following it to its final destination in the hepatocyte. RESULTS: Despite its abundant presence in plasma, adiponectin is cleared rapidly with a half-life of approximately 75 min. A more bioactive version carrying a mutation at cysteine 39 is cleared within minutes. Even though steady-state levels of adiponectin differ between male and female mice, we failed to detect any differences in clearance rates, suggesting that differences in plasma are mostly due to differential production rates. In a metabolically challenged state (high-fat diet exposure or in an ob/ob background), adiponectin levels are reduced in plasma and clearance is significantly prolonged, reflecting a dramatic drop in adiponectin production levels. CONCLUSIONS: Combined, these results show a surprisingly rapid turnover of adiponectin with multiple fat pads contributing to the plasma levels of adiponectin and clearance mediated primarily by the liver. It is surprising that despite high-level production and rapid clearance, plasma levels of adiponectin remain remarkably constant.

Adiponectin gene therapy of streptozotocin-induced diabetic mice using hydrodynamic injection.

BACKGROUND: Adiponectin (Adipo), an adipocyte hormone involved in the regulation of glucose and lipid metabolism, has already been identified as a potential therapeutic target for the treatment of diabetes. However, successful delivery of Adipo to the receptors is difficult due to their peptide characteristics. Receptors for Adipo are abundantly expressed in the liver and skeletal muscle. METHODS: Uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) in hepatoblastoma HepG2 cells expressing Adipo was examined. Adipo-expressing plasmid DNA (10-50 microg) in saline solution (0.1 ml/g body weight) was rapidly injected into the tail vein of 4-week-old diabetic mice after 4-6 weeks of treatment with streptozotocin (STZ). Uptake of glucose in diabetic mice also was measured using a planar positron imaging system featuring 18-fluorodeoxyglucose. RESULTS: HepG2 cells expressing Adipo exhibited significantly increased 2-NBDG uptake compared with cells transfected with control plasmid even in the absence of insulin. STZ-induced diabetic mice showed decreased serum Adipo levels compared with non-diabetic mice. A single hydrodynamic injection of 10-50 microg Adipo-expressing plasmid DNA into diabetic mice led to approximately 10-15-fold elevation in serum Adipo levels, and resulted in decreased serum levels of glucose and triglyceride. As well as exhibiting higher levels of Adipo expression, diabetic mice also had higher hepatic glucose uptake than similar mice injected with control plasmid. CONCLUSIONS: We report that STZ-induced diabetic mice exhibited decreased Adipo levels and hyperglycemia which may be alleviated by hydrodynamic injection of the Adipo gene. This type of gene delivery system to the liver offers a different approach in developing novel treatments for type 1 and 2 diabetes.

Fat-derived hormone adiponectin combined with FTY720 significantly improves small-for-size fatty liver graft survival.

Owing to the discrepancy between organ donation and the demand for liver transplantation, expanding the liver donor pool is of vital importance. However, marginal liver grafts, such as small-for-size and/or fatty grafts, were associated with primary graft nonfunction or poor function. Therefore, novel combination therapies to rescue small-for-size fatty liver grafts should be investigated. In this study, we applied a combination therapy using a fat-derived hormone adiponectin (anti-steatosis) plus immunomodulator FTY720 (anti-inflammatory) in a rat liver transplantation model using small-for-size fatty liver grafts, and investigated the underlying protective mechanism such as anti-steatosis, intra-graft energy metabolism, hepatic microcirculatory changes, cell signaling cascades for survival, apoptosis and inflammation. The current study demonstrated that even a single treatment of adiponectin or FTY720 improved the 7-day graft survival from 0% to 62.5% (p = 0.001). The combination therapy significantly increased the 7-day graft survival rate to 100% by remarkable attenuation of graft steatosis and acute phase inflammatory response, significant activation of cell survival Akt pathway and maintenance of intra-graft adenosine triphosphate metabolism and improvement of hepatic microcirculation. In conclusion, the fat-derived hormone adiponectin combined with FTY720 might be a novel combination drug therapy for prevention of small-for-size fatty liver graft injury.