**15. Impaired vascular structure and function**

Several studies in humans and animal models have shown that obesity induces capillary rarefaction in adipose tissue, and this has been associated with metabolic dysfunction. It is widely a reduced adipose tissue; capillarization is present in obesity, and this reduced blood supply may limit nutrient delivery and contribute to adipocyte dysfunction and insulin resistance.

Evidence of a causal role of adipose tissue vascularization in obesity-associated metabolic dysfunction have been shown in recent studies with genetically engineered mice. Experiments demonstrated that an increased VEGF-mediated angiogenesis in adipose tissue can attenuate some of the metabolic effects of diet-induced obesity, such as insulin resistance and hepatic steatosis in mice overexpressing vascular endothelial growth factor A (VEGF-A) in adipocytes. Conversely, adipocyte-restricted deletion of VEGF-A results in diminished adipose tissue vascularization, which leads to increased adipose tissue inflammation and systemic metabolic dysfunction further supporting the noxious effects of reduced adipose tissue vascularity in obesity [48–51].

### **16. Adipose tissue fibrosis**

Within the adipose tissue of lean organisms, adipocytes are surrounded by extracellular matrix that provides mechanical support and participates in cell signaling. There is a general increase in the synthesis of several extracellular matrix components with the development of obesity, in particular collagen VI, which leads to adipose tissue fibrosis and is associated with impaired metabolic function in mice. Adipose tissue fibrosis is increased in both subcutaneous and visceral depots in obesity. Obesity-induced adipose tissue fibrosis is due, at least in part, to hypoxiainduced upregulation of hypoxia-inducible factor 1α (HIF1α). Interestingly, HIF1α activation does not contribute to an angiogenic response in this context, but instead promotes adipose tissue fibrosis [52].

#### **17. Conclusions**

An increasing evidence supports the evolving concept that quality, quantity, and location of adipose tissue are critical factors in shaping cardiometabolic phenotypes in obese individuals. The specific pathogenic mechanisms and their relative contributions remain incompletely understood. Adipose tissue communicates with remote organs, including the heart and vasculature, through the release of various adipokines. While some adipokines have been highly studied and have shown to be causally linked to various disease processes, new adipokine candidates continue to be discovered and elucidated. In murine models and many human individuals, obesity leads to adipose tissue dysfunction; this dysfunction is termed adiposopathy, particularly in visceral fat depots, which is mediated by dysfunctional tissue remodeling that involves adipocyte hypertrophy, increased fibrosis exacerbated inflammation, and impaired vascular function and structure. This ultimately creates a chronic, low-grade systemic inflammatory reaction mediated by an imbalance in adipokine levels which contributes to the initiation and progression of metabolic and cardiovascular complications. As our understanding of adipokines and obesityinduced adiposopathy increases, the major challenge will reside in translating this information into new prognostic and therapeutic approaches to limit cardiovascular risk in obese individuals. Considering that a third of the world's population is currently overweight or obese and this proportion is expected to increase in the coming decades, studies of adipokine biology should provide a better understanding of the pathogenesis of cardiovascular disease.

**93**

**Author details**

Marco Antonio Lopez Hernandez

Mexico's State, State of Mexico, Mexico

\*Address all correspondence to: niklaus2003@yahoo.com.mx

provided the original work is properly cited.

*Obesity-Related Myocardiopathy*

*DOI: http://dx.doi.org/10.5772/intechopen.85949*

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Internal Medicine Division, Ecatepec General Hospital, Autonomous University of

*Obesity-Related Myocardiopathy DOI: http://dx.doi.org/10.5772/intechopen.85949*

*Visions of Cardiomyocyte - Fundamental Concepts of Heart Life and Disease*

tissue vascularity in obesity [48–51].

promotes adipose tissue fibrosis [52].

pathogenesis of cardiovascular disease.

**17. Conclusions**

**16. Adipose tissue fibrosis**

Evidence of a causal role of adipose tissue vascularization in obesity-associated metabolic dysfunction have been shown in recent studies with genetically engineered mice. Experiments demonstrated that an increased VEGF-mediated angiogenesis in adipose tissue can attenuate some of the metabolic effects of diet-induced obesity, such as insulin resistance and hepatic steatosis in mice overexpressing vascular endothelial growth factor A (VEGF-A) in adipocytes. Conversely, adipocyte-restricted deletion of VEGF-A results in diminished adipose tissue vascularization, which leads to increased adipose tissue inflammation and systemic metabolic dysfunction further supporting the noxious effects of reduced adipose

Within the adipose tissue of lean organisms, adipocytes are surrounded by extracellular matrix that provides mechanical support and participates in cell signaling. There is a general increase in the synthesis of several extracellular matrix components with the development of obesity, in particular collagen VI, which leads to adipose tissue fibrosis and is associated with impaired metabolic function in mice. Adipose tissue fibrosis is increased in both subcutaneous and visceral depots in obesity. Obesity-induced adipose tissue fibrosis is due, at least in part, to hypoxiainduced upregulation of hypoxia-inducible factor 1α (HIF1α). Interestingly, HIF1α activation does not contribute to an angiogenic response in this context, but instead

An increasing evidence supports the evolving concept that quality, quantity, and

location of adipose tissue are critical factors in shaping cardiometabolic phenotypes in obese individuals. The specific pathogenic mechanisms and their relative contributions remain incompletely understood. Adipose tissue communicates with remote organs, including the heart and vasculature, through the release of various adipokines. While some adipokines have been highly studied and have shown to be causally linked to various disease processes, new adipokine candidates continue to be discovered and elucidated. In murine models and many human individuals, obesity leads to adipose tissue dysfunction; this dysfunction is termed adiposopathy, particularly in visceral fat depots, which is mediated by dysfunctional tissue remodeling that involves adipocyte hypertrophy, increased fibrosis exacerbated inflammation, and impaired vascular function and structure. This ultimately creates a chronic, low-grade systemic inflammatory reaction mediated by an imbalance in adipokine levels which contributes to the initiation and progression of metabolic and cardiovascular complications. As our understanding of adipokines and obesityinduced adiposopathy increases, the major challenge will reside in translating this information into new prognostic and therapeutic approaches to limit cardiovascular risk in obese individuals. Considering that a third of the world's population is currently overweight or obese and this proportion is expected to increase in the coming decades, studies of adipokine biology should provide a better understanding of the

**92**
