Low fat adiponectin expression is associated with oxidative stress in nondiabetic humans with chronic kidney disease—impact on plasma adiponectin concentration

Abstract

In spite of association between high plasma adiponectin and high metabolic and cardiovascular (CV) risk, highest adiponectin increments retain CV and metabolic protective effects in advanced chronic kidney disease (CKD). Passive accumulation can favor CKD-associated hyperadiponectinemia but potential additional regulation by adipose tissue remains undefined. Oxidative stress (OS) is associated with metabolic and CV disease and with CKD [increasing from conservative treatment (CT) to maintenance hemodialysis (MHD)], and OS can reduce adiponectin expression in experimental models. OS (in the form of plasma thiobarbituric acid-reactive substances: TBARS), subcutaneous adipose adiponectin mRNA, and plasma adiponectin were studied in CKD patients (stages 4 and 5) on CT (n = 7) or MHD (n = 11). Compared with CT and controls (C: n = 6) MHD had highest TBARS and lowest adiponectin mRNA (P < 0.05) with lower adipose adiponectin protein (P < 0.05 vs. CT). MHD also had lower plasma adiponectin than CT, although both had higher adiponectin than C (P < 0.05). In renal transplant recipients (RT: CKD stage 3; n = 5) normal TBARS were, in turn, associated with normal adiponectin mRNA (P < 0.05 vs. MHD). In all CKD (n = 23), adiponectin mRNA was associated positively with adiponectin plasma concentration (P < 0.01). In all subjects (n = 29), adiponectin mRNA was related (P < 0.05) negatively with TBARS after adjusting for plasma C-reactive protein (CRP) or CRP and creatinine. Thus altered OS, adiponectin expression, and plasma concentration represent a novel cluster of metabolic and CV risk factors in MHD that are normalized in RT. The data suggest novel roles of 1) MHD-associated OS in modulating adiponectin expression and 2) adipose tissue in contributing to circulating adiponectin in advanced CKD.

Combined effects of ghrelin and higher food intake enhance skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rats with chronic kidney disease

“…Systemic inflammation is common in CKD24,30 and was activated in the current model as indicated by proinflammatory changes in circulating cytokines 16. Ghrelin treatment resulted in lower plasma concentrations of proinflammatory cytokines,16 consistent with reported in vitro anti-inflammatory ghrelin effects 31.…”

Glomerular and tubular dysfunctions and their relationship to adiponectin and oxidative stress in obese subjects

“…Similar results have been shown in other studies. 45,46 The present results indicate that the increased OS in obese individuals can be explained by the decreased adiponectin level that may lead to deficiency of the protective HDL-C. As it was found that there is a strong inverse association between adiponectin and fractional catabolic rate of ApoA-1 which is a major structural apolipoprotein of HDL-C. 47 Deficiency of HDL-C in obese individuals was associated with elevated levels of oxidative stress and impairment of its antioxidant effects. 48 In this work, albuminuria was positively correlated with TBARs and negatively correlated with adiponectin.…”

Inverse Relationship between the Inflammatory Marker Pentraxin-3, Fat Body Mass, and Abdominal Obesity in End-Stage Renal Disease

“…In the general population, systemic clinical hypoadiponectinemia is closely associated with obesity, type 2 diabetes, and coronary artery disease, and the increased oxidative stress in adipose tissue that accumulates in obesity associates with decreased adiponectin production (36). In CKD patients, reduction in oxidative stress through blockade of the angiotensin II type 1 receptor ameliorates adiponectin concentration (37), and oxidative stress is an important determinant of low fat adiponectin expression (38). A similar oxidative stress-related mechanism might also, at least in part, affect PTX3 production in adipocytes.…”