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Obesity and Cardiometabolic Defects in Heart Failure Pathology

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ABSTRACT

Obesity is a major global epidemic that sets the stage for diverse multiple pathologies, including cardiovascular disease. The obesity‐related low‐grade chronic inflamed milieu is more pronounced in aging and responsive to cardiac dysfunction in heart failure pathology. Metabolic dysregulation of obesity integrates with immune reservoir in spleen and kidney network. Therefore, an integrative systems biology approach is necessary to delay progressive cardiac alternations. The purpose of this comprehensive review is to largely discuss the impact of obesity on the cardiovascular pathobiology in the context of problems and challenges, with major emphasis on the diversified models, and to study cardiac remodeling in obesity. The information in this article is immensely helpful in teaching advanced undergraduate, graduate, and medical students about the advancement and impact of obesity on cardiovascular health. © 2017 American Physiological Society. Compr Physiol 7:1463‐1477, 2017.

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Figure 1. Figure 1. Obesity and related metabolic dysregulation set the platform for a vicious proinflammatory environment for post‐MI pathology with marked dysregulation of the cardiosplenic and cardiorenal network in heart failure pathology. Bone marrow adiposity, particularly in obese, diabetes and aging populations, supplies proinflammatory monocytes and enhances the atherosclerotic conditions that simulate an MI event as well as subsequent renal and pulmonary edema and chronic inflammation in heart failure pathology. Increased macrophage (DAPI/F480/CD169‐red) density in aging mice kidney (18 months) compared with young mice (2 months old) shows chronic glomeruli inflammation.
Figure 2. Figure 2. Obesity superimposed on aging magnify nonresolving inflammation. Post‐MI acute inflammation triggers changes in the kinetics and leukocytes quantity from acute phase (d1‐d3), resolution phase (d3‐d7), and fibrotic/chronic phase (d5‐d28). This results in imbalance in generation of resolving and nonresolving lipid in the acute and resolving phases of myocardium healing thereby impaired resolution of inflammation. Levels of resolving and proinflammatory lipid mediators determine the resolving capacity of myocardium healing in heart failure pathology.
Figure 3. Figure 3. Multiple mediators generated in the spleen, adipose tissue, liver, and bone marrow contributes to myocardial healing. Adipokines (liver adiposity), bone marrow, and spleen collectively coordinate low‐grade inflammation in heart failure. The low‐grade inflammation is sustained during myocardial healing leading to impaired resolution of inflammation in obesity.
Figure 4. Figure 4. Diversity of lipid mediators derived from polyunsaturated n‐6 fatty acids and immunoresolvents derived from n‐3 fatty acid. Dietary sources of n‐3 and n‐6 fatty acids and their respective lipid metabolites are illustrated to define the differential chemical milieu responsive to dietary factors.
Figure 5. Figure 5. Fatty acid metabolism gene network and impaired fatty acid oxidation. Fatty acid intake alters the oxidative metabolism via direct and indirect interaction with the metabolic gene network that generates energy in homeostasis. The imbalance or over and or under activation of metabolic genes leads to lipotoxicity and heart failure.
Figure 6. Figure 6. Impact of salt‐ and fat‐enriched diets in obesity, diabetes, and hypertension leading to MI and heart failure events. Solid lines indicate direct contribution to pathology, and dotted lines indicate indirect effect. Mediterranean and DASH (dietary approaches to stop hypertension) diets show capacity of reducing the overall rate of cardiovascular disease and heart failure events.


Figure 1. Obesity and related metabolic dysregulation set the platform for a vicious proinflammatory environment for post‐MI pathology with marked dysregulation of the cardiosplenic and cardiorenal network in heart failure pathology. Bone marrow adiposity, particularly in obese, diabetes and aging populations, supplies proinflammatory monocytes and enhances the atherosclerotic conditions that simulate an MI event as well as subsequent renal and pulmonary edema and chronic inflammation in heart failure pathology. Increased macrophage (DAPI/F480/CD169‐red) density in aging mice kidney (18 months) compared with young mice (2 months old) shows chronic glomeruli inflammation.


Figure 2. Obesity superimposed on aging magnify nonresolving inflammation. Post‐MI acute inflammation triggers changes in the kinetics and leukocytes quantity from acute phase (d1‐d3), resolution phase (d3‐d7), and fibrotic/chronic phase (d5‐d28). This results in imbalance in generation of resolving and nonresolving lipid in the acute and resolving phases of myocardium healing thereby impaired resolution of inflammation. Levels of resolving and proinflammatory lipid mediators determine the resolving capacity of myocardium healing in heart failure pathology.


Figure 3. Multiple mediators generated in the spleen, adipose tissue, liver, and bone marrow contributes to myocardial healing. Adipokines (liver adiposity), bone marrow, and spleen collectively coordinate low‐grade inflammation in heart failure. The low‐grade inflammation is sustained during myocardial healing leading to impaired resolution of inflammation in obesity.


Figure 4. Diversity of lipid mediators derived from polyunsaturated n‐6 fatty acids and immunoresolvents derived from n‐3 fatty acid. Dietary sources of n‐3 and n‐6 fatty acids and their respective lipid metabolites are illustrated to define the differential chemical milieu responsive to dietary factors.


Figure 5. Fatty acid metabolism gene network and impaired fatty acid oxidation. Fatty acid intake alters the oxidative metabolism via direct and indirect interaction with the metabolic gene network that generates energy in homeostasis. The imbalance or over and or under activation of metabolic genes leads to lipotoxicity and heart failure.


Figure 6. Impact of salt‐ and fat‐enriched diets in obesity, diabetes, and hypertension leading to MI and heart failure events. Solid lines indicate direct contribution to pathology, and dotted lines indicate indirect effect. Mediterranean and DASH (dietary approaches to stop hypertension) diets show capacity of reducing the overall rate of cardiovascular disease and heart failure events.
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Ganesh V. Halade, Vasundhara Kain. Obesity and Cardiometabolic Defects in Heart Failure Pathology. Compr Physiol 2017, 7: 1463-1477. doi: 10.1002/cphy.c170011