Adipokines, diabetes and atherosclerosis: an inflammatory association - PubMed (original) (raw)

Review

Adipokines, diabetes and atherosclerosis: an inflammatory association

Leandro C Freitas Lima et al. Front Physiol. 2015.

Abstract

Cardiovascular diseases can be considered the most important cause of death in diabetic population and diabetes can in turn increase the risk of cardiovascular events. Inflammation process is currently recognized as responsible for the development and maintenance of diverse chronic diseases, including diabetes and atherosclerosis. Considering that adipose tissue is an important source of adipokines, which may present anti and proinflammatory effects, the aim of this review is to explore the role of the main adipokines in the pathophysiology of diabetes and atherosclerosis, highlighting the therapeutic options that could arise from the manipulation of these signaling pathways both in humans and in translational models.

Keywords: IL-6; MCP-1; TNFα; adipokines; adiponectin; atherosclerosis; diabetes; leptin.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Over nutrition, metabolic syndrome and/or genetic predisposition may contribute to obesity development and modulate adipokine profile resulting in a low-grade inflammatory state which is associated with increased risk of insulin resistance and atherosclerosis.

Figure 2

Figure 2

Increase in adipose tissue mass is related to increase in MCP-1, which favors macrophages migration to adipose tissue and the production of other adipokines such as IL-6 and TNFα. On the other hand, obese adipose tissue produces less adiponectin. Taken together, these features reduce glucose uptake in muscle cells and favors glycogenolisis and gluconeogenesis in liver, which contribute to insulin resistance and diabetes.

Figure 3

Figure 3

In obesity, despite increased levels of leptin, central actions of this adipokine that control appetite, body weight, and energy expenditure are impaired (a phenomena known as leptin resistance, represented in the figure by the crossed red arrow from adipose tissue to the brain and black arrows). Otherwise, peripheral actions of leptin to reduce insulin secretion in pancreas and its signaling pathways is muscle (represented in the figure by plain arrows from adipose tissue to pancreas and muscle) culminates in insulin resistance, hyperglycemia and diabetes.

Figure 4

Figure 4

The process of atherogenesis can be influenced by diverse adipokines.1: Endothelial dysfunction (ED) and transmigration of LDL particles to subendothelial space can be worsen by leptin and TNFα. Adiponectin, which is reduced in obesity, recovers endothelial function. 2: Once in subendothelial space LDL is oxidized (oxLDL), which is positively related to MCP-1 levels. Leptin, IL-6, MCP-1 and TNFα increase the expression of adhesion molecules in endothelium and increase leucocyte transmigration. 3: Monocytes turn into macrophages under the stimulus of MCP-1 and phagocytes oxLDL, turning into foam cells. Adiponectin inhibits phagocytosis of oxLDL and foam cell formation. 4: IL-6 can be produced by local smooth muscle cells (SMC) under the stimulus of angiotensin II. Along with MCP-1, it increases recruitment and proliferation of SMC and extracellular matrix deposition to form a fibrous cap around a lipid-rich necrotic core. 5: Due to stimulation of matrix metalloproteinases and prothrombotic molecules, MCP-1 and leptin favors plaque rupture and thrombus formation, while adiponectin inhibits thrombosis. Periadventitial adipose tissue (PAAT) and leptin induce the production of proinflammatory adipokines. Red arrows represent proinflammatory pathways which are stimulated during obesity and contribute to atherogenesis. Blue arrows represent anti-inflammatory pathways which are inhibited during obesity since adiponectin levels are low. Green arrows represent production or stimulation of adipokine secretion.

Similar articles

Cited by

References

    1. Adya R., Tan B. K., Randeva H. S. (2015). Differential effects of leptin and adiponectin in endothelial angiogenesis. J. Diabetes Res. 2015, 1–12. 10.1155/2015/648239 - DOI - PMC - PubMed
    1. Ahima R. S., Flier J. S. (2000). Leptin. Annu. Rev. Physiol. 62, 413–437. 10.1146/annurev.physiol.62.1.413 - DOI - PubMed
    1. American Diabetes Association (2014). Standards of medical care in diabetes—2014. Diab. Care. 37. 10.2337/dc14-S014 - DOI - PubMed
    1. Amitani M., Asakawa A., Amitani H., Inui A. (2013). The role of leptin in the control of insulin-glucose axis. Front. Neurosci. 7:51. 10.3389/fnins.2013.00051 - DOI - PMC - PubMed
    1. Arita Y., Kihara S., Ouchi N., Takahashi M., Maeda K., Miyagawa J., et al. . (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. 257, 79–83. 10.1006/bbrc.1999.0255 - DOI - PubMed

Publication types

LinkOut - more resources