Reciprocal Effects of Systemic Inflammation and Brain Natriuretic Peptide on Adiponectin Biosynthesis in Adipose Tissue of Patients With Ischemic Heart Disease

Abstract

Objective-To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease. Approach and Results-In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged. Conclusions-This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.

Correlation between adiponectin and hemorrhagic shock in mice

“…Many studies have documented the involvement of ADPN in the termination of inflammation by at least two mechanisms: the first is through the inhibition of the function of mature macrophages and the second is the growth of granulocyte-monocyte progenitor cell lines. The former mechanism plays an important role in acute inflammation while the latter mechanism plays a major role in chronic inflammation in order to avoid excessive immune response (Antonopoulos et al, 2014;Cao et al, 2014;Li et al, 2015). Additionally, the findings in our present study demonstrate that the serum level of ADPN in mice increase in the early period of HS, which is in accordance with the varying trend of IL-37 in the same HS model.…”

Adiponectin Regulation in Cardiovascular Disease

“…These findings suggest that adiponectin regulation is more complicated than originally thought. The study of Antonopoulos et al 12 in the September 2014 issue of Arteriosclerosis, Thrombosis, and Vascular Biology indeed shows that interpretation of adiponectin regulation in plasma and adipose from heart disease patients is complex and dependent on different processes involved in CVD progression.…”

“…Still, the study by Antonopoulos et al 12 provides the reader with an interesting novel concept of variability in adipocyte responsiveness in healthy and diseased adipose tissue. Furthermore, it is clearly established that cardiac-derived BNP is the critical denominator of adiponectin responses in patients with severe CVD (Figure).…”

Unravelling the “adipokine paradox”: When the classic proatherogenic adipokine leptin is deemed the beneficial one

“…Adipokines are also known to affect the vascular wall and the human heart in an endocrine manner through the systemic circulation or even in a paracrine manner via their release from local depots such as perivascular or epicardial adipose tissue [3,4].…”

“…We have previously highlighted that the use of plasma adipokine levels as biomarkers needs caution given the complex cross-talk between adipose tissue and the cardiovascular system [4]. For example, our previous findings suggest that adiponectin functions as a 'stress hormone' and its biosynthesis from adipose tissue is upregulated by the effects of natriuretic peptides in patients with ischemic heart disease [4].…”