Increased albuminuria is associated with obesity and diabetes and is a risk factor for cardiovascular and renal disease. However, the link between early albuminuria and adiposity remains unclear. To determine whether adiponectin, an adipocyte-derived hormone, is a communication signal between adipocytes and the kidney, we performed studies in a cohort of patients at high risk for diabetes and kidney disease as well as in adiponectin-knockout (Ad(-/-)) mice. Albuminuria had a negative correlation with plasma adiponectin in obese patients, and Ad(-/-) mice exhibited increased albuminuria and fusion of podocyte foot processes. In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane. These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes. Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress. These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.

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Adiponectin regulates albuminuria and podocyte function in mice

Obesity is a risk factor for chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD). Recent studies identify mechanisms common to both diseases linked through an interorgan communication orchestrated by fetuin-A and adiponectin. In liver and kidney, the energy sensor 5′-AMP activated protein kinase (AMPK) is pivotal to directing podocytes and hepatocytes to compensatory and potentially deleterious pathways, leading to inflammatory and profibrotic cascades culminating in end-organ damage. Regulation of these early upstream pathways may provide new therapeutic targets for these increasingly common sequelae of obesity.

Mechanisms Linking Obesity, Chronic Kidney Disease, and Fatty Liver Disease: The Roles of Fetuin-A, Adiponectin, and AMPK

Purpose of reviewAdiponectin is secreted exclusively by adipocytes, aggregates in multimeric forms, and circulates at high concentrations in blood. This review summarizes recent studies highlighting cellular effects of adiponectin and its role in human lipid metabolism and atherosclerosis.Recent fin

Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease.

White adipose tissue, previously regarded as a passive lipid storage site, is now viewed as a dynamic tissue. It has the capacity to actively communicate by sending and receiving different types of signals. An overview of these signals, the external modulators that affect adipose tissue and the secreted signaling molecules, the adipokines, is presented. The secretory function is highlighted in relation to energy metabolism, inflammation and the extracellular matrix and placed in the context of adipose tissue biology. We observe that the endocrine function of adipocytes receives much attention, while its paracrine and autocrine functions are underestimated. Also, we provide examples that species specificity should not be neglected. We conclude that adipose tissue primarily is an energy storage organ, well supported by its secretory function.

The secretory function of adipocytes in the physiology of white adipose tissue

There are controversies regarding the association of visfatin with overweight/obesity, type 2 diabetes mellitus, insulin resistance (IR), metabolic syndrome and cardiovascular disease in published articles. A meta-analysis was performed to identify the significance of visfatin in these diseases. We searched for relevant articles in Pubmed, Scopus and SCIE. A total of 1035 articles were surveyed and 46 articles were identified, with 14 reports reporting more than one of our investigated diseases. A total of 13 (n = 644), 19 (n = 2405), 20 (n = 2249), 5 (n = 527) and 5 (n = 851) articles/(participants) were included in each meta-analysis regarding the association of visfatin and overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases, respectively. Plasma visfatin concentrations were increased in participants diagnosed with overweight/obesity, type 2 diabetes mellitus, metabolic syndrome and cardiovascular diseases, with pooled log odds ratios of 1.164 [95% confidence interval (CI): 0.348 to 1.981, p = 0.005], 1.981 (95% CI: 1.377 to 2.584, p < 0.001), 1.094 (95% CI: 0.678 to 1.511, p < 0.001), and 2.902 (95% CI: 0.924 to 4.879, p < 0.005), respectively. The circulating visfatin level was positively associated with insulin resistance, with a Fisher's z of 0.089 (95% CI: 0.013 to 0.165, p = 0.022). No single study was found to affect the overall result of each analysis by sensitivity testing. No publication bias was found by the Egger test. Our study suggests that the use of visfatin may be promising for predicting obesity, diabetes status, insulin resistance, metabolic syndrome and cardiovascular disease.

Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta‐analysis and systemic review

Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance.

Hypercholesterolemia is a major risk factor for atherosclerosis. Dysregulation of adipokines contribute to atherosclerotic diseases. Apelin has recently been shown to be secreted by the adipose tissue in association with hyperinsulinemia and inflammation. We searched plasma apelin levels in patients with elevated low density lipoprotein (LDL)-cholesterol having no additional disorder. Thirty-three patients with hypercholesterolemia and 50 age-, sex-, and body mass index-matched healthy controls were evaluated for their apelin, adiponectin and high sensitivity C-reactive protein (hsCRP) levels, and homeostasis model assessment (HOMA) indexes. Plasma apelin-12 and adiponectin were determined by ELISA and RIA, respectively. Plasma apelin levels were lower in patients with elevated LDL-cholesterol compared to healthy controls (p<0.001). Plasma adiponectin concentration was also lower in the dyslipidemic patients (p<0.001). hsCRP levels were similar in the two groups. Fasting plasma glucose was normal in both groups. HOMA indexes in the dyslipidemic group were higher than the controls (p=0.005). A mild to moderate negative correlation with HOMA and positive correlation with high density lipoprotein cholesterol of apelin was found in the dyslipidemic group. Plasma apelin is decreased in non-obese, non-diabetic and normotensive patients with elevated LDL-cholesterol. Low apelin levels in hypercholesterolemia seem associated with insulin resistance, which needs to be investigated in larger populations as well as in other atherosclerotic conditions.

Plasma apelin is lower in patients with elevated LDL-cholesterol.

Psoriasis is a common inflammatory skin disease, and conflicting data have been published about osteoporosis and bone turnover markers in patients with psoriatic arthritis. The aim of this study was to assess bone mineral density (BMD) and bone turnover markers in psoriatic patients with and without peripheral arthritis and to investigate the relationship between clinical parameters and markers of bone turnover. Forty-seven patients (24 women, 23 men) with psoriasis were included to the study. Demographic data and clinical characteristics were recorded. Erythrocyte sedimentation rate and C-reactive protein were assessed as disease activity parameters. BMD was determined for lumbar spine and total hip by dual X-ray absorptiometry (DXA). Serum Ca, P, alkalen phosphatase (ALP), and serum type I collagen cross-linked C telopeptide (CTX) were measured as bone turnover markers in all patients. The patients were divided into two groups according to their peripheral arthritis status. The clinical and laboratory variables, as well as bone mass status of the groups, were compared with each other. Eighteen patients had peripheral arthritis. All the female patients were premenopausal. None of the patients had radiologically assessed axial involvement. There was no significant difference between the BMD levels of psoriatic patients with and without arthropathy. One patient (5%) had osteoporosis, and nine (50%) patients had osteopenia in arthritic group, while eight (27.5%) patients had osteopenia in patients without arthritis. Serum CTX, ALP, Ca, and P levels were not significantly different in arthritic than in non-arthritic patients (p > 0.05). In patients with psoriatic arthritis, the duration of arthritis was negatively correlated with BMD values of lumbar spine and total femur and serum CTX levels, suggesting an association of increased demineralization with the duration of joint disease. In conclusion, psoriatic patients with peripheral arthritis with longer duration of joint disease may be at a risk for osteoporosis, which can require preventative treatment efforts.

Bone mineral density and bone turnover in patients with psoriatic arthritis.

Background/Aims: Adiponectin seems to be an important modulator for metabolic and vascular diseases. A case study was designed to measure plasma adiponectin levels and to investigat

Blockade of the renin-angiotensin system increases plasma adiponectin levels in type-2 diabetic patients with proteinuria.

Conflicting data have been published about osteoporosis and bone turnover markers in patients with ankylosing spondylitis (AS). The aim of this study was to determine bone mineral density (BMD) of the lateral lumbar spine in a group of male patients with AS and to investigate the relationship between clinical parameters and markers of bone turnover. Thirty-two consecutive AS patients with a mean disease duration of 14.8 years and 32 control subjects were included. Demographic and clinical characteristics were recorded. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to determine the activity of disease. BMD was determined for the lateral lumbar spine in both patients and control groups. Serum osteocalcin and urinary N-telopeptide were measured as bone turnover markers in patient and control groups. Although the mean values of lumbar BMD in AS patients tended to be lower than in the control group, the difference was not statistically significant. Osteoporosis was observed in 11 (34.3%) of AS patients and in 2 (6.2%) of the control group. Osteocalcin levels were significantly higher in AS patients in comparison with control subjects (p < 0.05). In the subgroup analysis according to the activity of the disease, erythrocyte sedimentation rate and N-telopeptide levels were significantly higher in the severely active group when compared with that in mild or moderate disease groups. Active AS patients compared with the control group had significantly lower BMD and significantly higher N-Telopeptide levels (p < 0.05). The levels of BASDAI scores and N-telopeptide values correlated significantly with each other. The incidence of osteoporosis is high in AS patients, and patients with active disease are especially at risk for developing osteoporosis. The monitoring of bone turnover markers and disease activity indices may help to predict patients at risk. Prophylactic and therapeutic strategies are needed to struggle against bone loss in patients with this disabling condition.

Sezin Bingol

Papers

Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance.

Plasma apelin is lower in patients with elevated LDL-cholesterol.

Bone mineral density and bone turnover in patients with psoriatic arthritis.

Blockade of the renin-angiotensin system increases plasma adiponectin levels in type-2 diabetic patients with proteinuria.

Bone mineral density and bone turnover markers in a group of male ankylosing spondylitis patients: relationship to disease activity.