We, therefore, quantified the levels of adiponectin (and leptin for direct . It is well established that leptin mRNA levels and secretion rates are. doses of adiponectin and leptin, but only partially by adminis- tration of . The relation between serum adiponectin and leptin and insulin. The role of endocrine actions of adiponectin and changes in local production of between adiponectin gene +45 and +G SNPs with obesity, type 2 diabetes, insulin .. Unfortunately it was not possible to quote all relevant literature and we . Relationship between high circulating adiponectin with bone mineral density.
In addition, several tissues can also produce adiponectin solid gray arrow which can then act locally twisted gray arrow to mediate functional autocrine or paracrine effect. Local effects of adiponectin may also be determined by changes in expression of its receptor isoforms and signaling intermediates, although relatively little is known on this topic to date.
Weight loss induced by either exercise or diet together with exercise enhance the expression of adiponectin receptor mRNA in skeletal muscle of humans and animal models Vu et al. A study in non-diabetic Mexican Americans with or without a family history of Type 2 diabetes concluded that skeletal muscle expression levels of both AdipoR1 and AdipoR2 correlated positively with insulin sensitivity Civitarese et al.Leptin & Insulin Resistance Balancing Tips w/ Jason Fung, MD
Hyperglycemia and hyperinsulinemia can both alter AdipoR expression in muscle cells and consequently adiponectin sensitivity Fang et al.
Bariatric surgery corrected hyperglycemia and this was correlated with increased circulating adiponectin and skeletal muscle AdipoR1 expression with reduced APPL1 content Holmes et al.
Cardiovascular As described above, many studies have established correlations between circulating adiponectin levels and various cardiovascular outcomes and the underlying mechanisms are now well understood.
For example, adiponectin is now established as a cardioprotective adipokine as it mediates beneficial effects on cardiac remodeling events such as energy metabolism, hypertrophy, fibrosis, and apoptosis Shibata et al.
Anti-inflammatory, vasodilator, and anti-atherosclerotic effects confer further beneficial influences of adiponectin on the cardiovascular system Fantuzzi, ; Brochu-Gaudreau et al. Mice lacking adiponectin have been particularly informative in establishing the cardioprotective role of adiponectin, with numerous studies in these mice demonstrating an exaggerated response of the heart to cardiac stress Shibata et al.
The ability of adiponectin to counteract deterioration in cardiac function was mediated by metabolic, anti-apoptotic, anti-fibrotic, and anti-hypertrophic effects Shibata et al. In cell based in vitro studies of isolated cardiomyocytes, adiponectin was shown to stimulate the phosphorylation of AMPK, IRS1, and Akt T and S correlating with the regulation of glucose and fatty acid uptake and metabolism Palanivel et al.
Recently Fang et al. However, despite an increase in fatty acid oxidation and myocardial oxygen consumption, adiponectin increased hydraulic work, and maintained cardiac efficiency Fang et al. Cardiac fibrosis is associated with impaired cardiac function, and there are numerous studies demonstrating the exaggerated fibrotic response of the heart to cardiac stress in the absence of adiponectin Shibata et al.
Very few studies have directly investigated regulation of extracellular matrix components by adiponectin in vitro.
Cardiac fibroblasts express AdipoR1 Huang et al. Although an overwhelming amount of data indicates numerous beneficial effects of adiponectin, there is also some contradictory evidence from clinical and experimental studies on the cardioprotective role of adiponectin.
For example, recent clinical data have positively correlated high levels of adiponectin with mortality and severity in patients with congestive heart failure Shinmura, Both cardiomyocytes Pineiro et al. Indeed, epicardial adipose-derived adiponectin was recently identified as a predictor of positive outcome following cardiac surgery Kourliouros et al.
Similarly, cardiomyocytes produce relatively small amounts of adiponectin Pineiro et al.
A number of studies have found that cardiac adiponectin levels are altered in various cardiomyopathies. For example, a recent study has shown in patients with dilated cardiomyopathy that adiponectin expression was decreased sixfold and this was mirrored in immunohistochemical analysis of endomyocardial biopsies Skurk et al.
Additionally, the accumulation of adiponectin within the myocardial tissue following stress through leakage from the vascular compartment could also serve to increase the local supply of bioavailable adiponectin and serve to compensate for the inflammatory induced downregulation of both local and systemic adiponectin expression Ouchi et al.
Interestingly, adiponectin has also been shown to accumulate in atherosclerotic plaques and whether this is causative or protective against progression of atherosclerosis is still incompletely resolved, although the latter seems most likely Li et al. Myocardial adiponectin resistance Saito et al. Overall, circulating or local adiponectin levels tend to correlate negatively with cardiovascular disease incidence and prognosis, however since many cardiovascular events are progressive in nature there may in some cases be a temporal compensatory increase in adiponectin expression, particularly within the affected tissue.
Thus, several paradoxical observations have been reported in the literature and it is likely that the timing of targeting adiponectin therapeutically will be vital to its success in the cardiovascular arena Dembinski, Liver Regulation of hepatic glucose and fatty acid metabolism plays an important role in the ability of adiponectin to improve whole body energy homeostasis Kadowaki and Yamauchi, ; Fang and Sweeney, ; Kadowaki et al.
For example, low levels or defects in adiponectin action correlate with steatosis, hepatomegaly, and local inflammation associated with various liver diseases. The intracellular signaling mechanisms via which adiponectin mediates effects in hepatocytes are similar to those in muscle Wang et al.
A role for T-cadherin has also been proposed in mediating the effects of adiponectin on liver fibrosis Asada et al. Furthermore, circulating adiponectin levels have been found to be downregulated in morbidly obese patients with non-alcoholic steatohepatitis NASH compared to individuals with simple steatosis Uribe et al.
Thus, a potentially detrimental contribution of adiponectin as NAFLD progresses to cirrhosis must be considered Polyzos et al. Hepatic AdipoR1 and AdipoR2 mRNA expression levels were higher in insulin-resistant subjects, perhaps reflecting a compensatory mechanism for reduced plasma adiponectin Felder et al.
Liver fibrosis in individuals infected with hepatitis C virus was associated with hyperadiponectinemia and, interestingly, reduced AdipoR1 expression Corbetta et al. In addition, liver expression and localization of adiponectin were increased in wild-type mice in response to carbon tetrachloride induced hepatofibrosis Yoda-Murakami et al. Lung Respiratory complications are often observed in obese individuals Ford, ; Shore, Importantly, decreased serum adiponectin levels correlate with poor lung function in asthma and chronic obstructive pulmonary disease COPD, independent of adiposity Sood et al.
Adiponectin knockout mice exhibited progressive alveolar enlargement and endothelial cell apoptosis, which was attenuated by adenoviral administration of adiponectin Nakanishi et al. Continuous infusion of adiponectin via subcutaneously implanted osmotic pumps to replenish decreased levels was found to attenuate ovalbumin-induced airway inflammation in mice through the attenuation of inflammatory cell influx, corresponding with a reduction in IL and IL-5 Shore et al. Furthermore, chronic allergic airway inflammation and pulmonary vascular remodeling are also exacerbated in adiponectin deficient mice Medoff et al.
Nevertheless, a double-blind randomized clinical trial found that asthmatic patients exhibited only a modestly beneficial effect in the late asthmatic response to inhaled allergen challenge after 28 days of rosiglitazone treatment to increase serum adiponectin levels Richards et al. Although the studies described above focused on endocrine effects of adiponectin, it is again important to consider the potential effects of locally produced adiponectin in the lung.
Adiponectin was found to be localized to the murine pulmonary vascular endothelium under normal Summer et al. Adiponectin was overexpressed in the bronchoalveolar lavage BAL fluid of COPD patients and in a multimeric distribution profile differing from that found in serum Zhu et al. Interestingly, these findings correlated with the increased localization of AdipoR1 to the airway epithelial cells of COPD patients Miller et al.
Others Numerous effects of adiponectin have been established in other peripheral tissues Kadowaki et al. For example, the longstanding complication of nephropathy in obesity and diabetes has naturally led to studies on the pathophysiological role of adiponectin in this process Chen et al. Increased circulating adiponectin levels are found in predialysis patients with end stage renal disease ESRD; Shen et al.
General consensus based on available literature indicates that adiponectin is renoprotective Abe et al. Even in the absence of a stressor, adiponectin deficient mice exhibited segmentally fused podocyte processes, increased albumin leakage into the urine albuminuriaand kidney oxidant stress when compared to wild-type controls, while treatment with adiponectin reduced the degree of albumin permeability of a podocyte monolayer in vitro Sharma et al.
Obesity is strongly associated with increased BMD due not only to the increased mechanical load, but also to adipocyte-derived hormonal factors mediating the cross-talk between adipocytes and bone Confavreux et al. As such, there is accumulating and contradictory evidence indicating that adiponectin plays a role in bone maintenance and metabolism Lenchik et al. Specifically, in vitro, adiponectin has been found to decrease osteoclast differentiation and bone-resorption activity Oshima et al.
However, additional studies in adiponectin deficient or hyperadiponectinemic examining bone mass and fragility yielded some paradoxical observations Oshima et al. Indeed, another study reported no abnormality in bone mass or turnover in adiponectin knockout mice or adiponectin transgenic mice overexpressing globular adiponectin Shinoda et al.
Interestingly, adiponectin has been found to be expressed by bone forming osteoblasts Berner et al. Adiponectin also has centrally mediated effects, such as regulation of food intake and energy expenditure Qi et al.
Although adiponectin was reportedly unable to cross the blood brain barrier Spranger et al. Several studies have documented the functionality of adiponectin Rodriguez-Pacheco et al. Adiponectin Action as a Therapeutic Target The rationale for targeting adiponectin is based on the well documented beneficial physiological actions of adiponectin spanning diabetes, inflammation, cardiovascular diseases, and cancer and it is expected that studies in animal models will translate well to human physiology in the case of adiponectin Mao et al.
Adiponectin-based therapeutics would have potentially wide-ranging applications in markets with widespread demographics. Synthesis and administration of recombinant forms of adiponectin is generally not a viable therapeutic approach due to the cost of synthesizing correctly posttranslationally modified bioactive forms and the disadvantage of the route of administration, although the recombinant globular domain of adiponectin is in pre-clinical trials for Merck and Protemix have a highly glycosylated form of adiponectin in pre-clinical trials.
Published online Sep Felczaka 3c, 71— Szczecin, Poland; E-Mail: Received Jun 12; Accepted Aug This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license http: This article has been cited by other articles in PMC.
Abstract The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers BMI from Anthropometric parameters were measured: The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch.
Introduction Cardiovascular disease CVDlike other chronic diseases, is the result of complex interactions between genetic and environmental factors over extended periods of time. CVD risk factors include metabolic e. Yet these classical risk factors only partly explain high cardiovascular risk and, in order to enhance the understanding of CVD and its treatment, tooresearch focusing on traditional as well as novel risk factors is still necessary to determine the most effective means of reducing unhealthy metabolic profiles.
The discovery of the endocrine function of adipose tissue has boosted the interest in its role in CVD and resulted in the reevaluation of many preconceived notions about this tissue [ 2 ]. Adipocytes are now known to have numerous receptors responsible for their sensitivity to humoral factors, allowing interactions between adipose tissue and the endocrine, cardiovascular, immune and nervous systems [ 3 ].
The significance of the endocrine function of adipose tissue is particularly evident in diseases accompanying abdominal obesity, diseases associated with dyslipidemia, elevated blood pressure, activation of prothrombotic and inflammatory processes, insulin resistance, atherosclerosis and impaired glucose tolerance, and therefore with type 2 diabetes T2DM and development of metabolic syndrome [ 345 ]. In addition, significant differences have been shown in recent years between subcutaneous and visceral fat, both in terms of the endocrine function and the released products [ 67 ].
The clinical significance of abdominal obesity is well known and is associated with adverse changes in lipid indicators and its relationship to increased risk of coronary heart disease, hypertension, metabolic syndrome and strokes [ 8 ]. Adipocytes secrete a variety of biologically active molecules which may influence the function and the structural integrity of the cardiovascular system, and may be involved in cardiovascular risk.
Nonetheless, the observed trends indicate that these adipokines may be used as adjunctive markers of metabolic disorders being associated with cardiovascular pathologies. Their other common feature is their distribution by adipocytes, and lesser known distribution by skeletal muscles and myocardium [ 91011 ].
However, their activities and roles are quite different. ADPN increases insulin sensitivity and fatty acid oxidation, reduces glucose synthesis and enhances glucose uptake by the liver and other tissues [ 1213 ]. LEP is mainly responsible for the regulation of food intake [ 9 ]; its higher serum levels inhibit hunger, increase energy expenditure by raising body temperature, while increasing fatty acid oxidation in the liver and skeletal muscle [ 14 ].
LEP has also been shown to be involved in immunological processes, hematopoiesis and probably in pathological processes, autoimmune diseases [ 1516 ], angiogenesis, hemostasis and wound healing [ 1718 ].
It is possible that ADPN and LEP may be the risk markers for fat-induced dyslipidemia or insulin resistance, with a risk for type 2 diabetes and cardiovascular disease.