Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease.
ABSTRACT Abdominal fat accumulation has been shown to play crucial roles in the development of metabolic syndrome. Visceral fat accumulation particularly is closely correlated to the development of cardiovascular disease and obesity-related disorders such as diabetes mellitus, hyperlipidemia and hypertension. Given these clinical findings, the functions of adipocytes have been intensively investigated in the past 10 years, and have been revealed to act as endocrine cells that secrete various bioactive substances termed adipocytokines. Among adipocytokines, tumor-necrosis factor-alpha, plasminogen activator inhibitor type 1 and heparin-binding epidermal growth factor-like growth factor are produced in adipocytes as well as other organs, and contribute to the development of vascular diseases. Visfatin has been identified as a visceral-fat-specific protein that might be involved in the development of obesity-related diseases, such as diabetes mellitus and cardiovascular disease. In contrast to these adipocytokines, adiponectin, which is an adipose-tissue-specific, collagen-like protein, has been noted as an important antiatherogenic and antidiabetic protein, or as an anti-inflammatory protein. The functions of adipocytokine secretion might be regulated dynamically by nutritional state. Visceral fat accumulation causes dysregulation of adipocyte functions, including oversecretion of tumor-necrosis factor-alpha, plasminogen activator inhibitor type 1 and heparin-binding epidermal growth factor-like growth factor, and hyposecretion of adiponectin, which results in the development of a variety of metabolic and circulatory diseases. In this review, the importance of adipocytokines, particularly adiponectin, is discussed with respect to cardiovascular diseases.
SourceAvailable from: Yoshihiro Kamada[Show abstract] [Hide abstract]
ABSTRACT: Background Obesity-related adipocytokine dysregulation is known to accelerate liver fibrosis progression. Recently, a natural Wnt5a inhibitor, secreted frizzled-related protein 5 (Sfrp5), was identified as a novel adipocytokine that has reduced expression in obese adipose tissue in both rodents and human. In addition, hepatic gene expression of Wnt5a and its receptor frizzled 2 (Fz2) is elevated during fibrosis progression. Therefore, Sfrp5 could have biological significance in liver fibrosis.Methods We first investigated the effects of Sfrp5 on primary cultured mouse hepatic stellate cells (HSCs) in vitro. Next, to elucidate the roles of Sfrp5 in liver fibrosis, we investigated a carbon-tetrachloride (CCl4)-induced liver fibrosis model using Sfrp5 knockout (KO) and wild type (WT) mice in vivo. Each mouse was injected intraperitoneally with CCl4 (0.5 ml/kg) or olive oil as a single dose (acute liver injury model), or twice a week for 6 weeks (liver fibrosis model).ResultsIn in vitro studies, Wnt5a enhanced both proliferation and migration of HSCs, and these effects could be completely blocked by Sfrp5. Moreover, siRNA knockdown of Fz2 in HSCs could block the effects of Wnt5a on both HSC proliferation and migration. In in vivo studies, there were no differences in the CCl4-induced liver injury between KO and WT mice. Hepatic Wnt5a gene expression and plasma Wnt5a levels significantly increased after a single CCl4 injection in both mice. Sfrp5 knockout significantly enhanced CCl4-induced liver fibrosis.Conclusions Our findings demonstrate that Sfrp5 may ameliorate mouse liver fibrosis through inhibition of Wnt5a/Fz2 signaling.This article is protected by copyright. All rights reserved.Liver international: official journal of the International Association for the Study of the Liver 12/2014; DOI:10.1111/liv.12757 · 4.41 Impact Factor
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ABSTRACT: To determine whether intrathoracic fat volumes are associated with presence and chronicity of atrial fibrillation (AF) and radiofrequency ablation (RFA) treatment outcome. IRB approval was obtained and patient consent was waived for this HIPAA-compliant retrospective study. 169 patients with AF (75 non-paroxysmal and 94 paroxysmal) and 62 control patients underwent cardiac CT examination. Extrapericardial (EPFV) and epicardial fat volumes (EFV) were measured on CT, the sum of which is the total intrathoracic fat volume. Associations between these three fat volumes and presence and chronicity of AF, and outcome after RFA, were evaluated using logistic regression analysis. EFV was significantly associated with presence [OR 1.01 (95 % CI 1.003-1.03), p = 0.01], chronicity of AF [1.008 (1.001-1.020), p = 0.03] and AF recurrence after RFA [1.009 (1.001-1.01), p = 0.02] after adjustment for age, gender and BMI. Patients with a larger EFV had a shorter time to AF recurrence (p = 0.017) and a higher rate of recurrence (54 % vs 46 %) (p = 0.002) after RFA. EPFV had no significant associations. Increased epicardial fat is associated with the presence and chronicity of AF, a higher probability of AF recurrence after RFA and a shorter AF-free interval. • Increased epicardial fat is associated with presence and chronicity of atrial fibrillation • Extensive epicardial fat is associated with earlier recurrences of AF after ablation • Extensive epicardial fat may reduce transmurality of ablation by affecting current dynamics.
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ABSTRACT: Osteoarthritis (OA) is one of the most common causes of musculoskeletal disability in the world. Traditionally, it has been thought that obesity contributes to the development and progression of OA by increased mechanical load of the joint structures. Nevertheless, studies have shown that adipose tissue-derived cytokines (adipocytokines) are a possible link between obesity and OA. Furthermore, according to recent findings, not only articular cartilage may be the main target of these cytokines but also the synovial membrane, subchondral bone and infrapatellar fat pad may be encompassed in the process of degradation. This review presents the most recent reports on the contribution of adipocytokines to the knee joint cartilage degradation, osteophyte formation, infrapatellar fat pad alterations and synovitis.International Orthopaedics 02/2015; DOI:10.1007/s00264-015-2707-9 · 2.02 Impact Factor