Pathological Role of Adipose Tissue Dysfunction in Cardio-Metabolic Disorders

Abstract

SummaryObesity has dramatically increased throughout the world, and has become one of the chief healthcare problems in many societies. Evidence has emerged that adipose tissue dysfunction associated with obesity is critically involved in the development of cardiovascular and metabolic disorders. In this review, we delineate the link between adipose tissue abnormalities and systemic metabolic dysfunction in patients with cardio-metabolic diseases and discuss the underlying mechanisms. (Int Heart J 2015; 56: 255-259) Key words: Aging, Diabetes, Insulin, Heart failure, White adipose tissue, Brown adipose tissue A ging can be characterized as an age-dependent decline of physiological function that leads to an increased risk of death. Chronological aging has been linked to genomic instability, loss of telomeres, epigenetic modifications, alterations of intercellular communication, and cellular senescence, all of which contribute to the pathology of aging and age-related disorders.1) The exact mechanism of aging is yet to be defined, but several factors have been reported to be involved. Calorie restriction and inhibition of insulin signaling are well known to delay the aging process and extend longevity in various species, including monkeys. 2)Obesity and diabetes have dramatically increased throughout world and have become major healthcare problems in many societies.3-6) Obesity has a central role in the development of diabetes and atherosclerotic disease, and being obese increases the risk of death, particularly from cardiovascular disease. 5,7,8) Systemic insulin resistance (hyperinsulinemia) is one of the crucial molecular mechanisms involved in the pathology of obesity and diabetes.9,10) Chronic low-grade sterile inflammation affecting visceral fat leads to systemic insulin resistance.11) Excessive uptake of free fatty acids by visceral fat in obese persons drives the production of reactive oxygen species (ROS) and initiates cellular senescence. Several lines of evidence have clearly shown a pathological role of cellular senescence in the progression of age-related diseases, such as atherosclerosis, obesity, and diabetes. 12,13) Recently, occurrence of cellular senescence in cardiac tissue and adipose tissue was reported to have a causal role in accelerating heart failure and diabetes, respectively. 14,15) Occurrence of cellular senescence in white adipose tissue (WAT) induces inflammation and systemic insulin resistance in a murine heart failure model, thus accelerating cardiac remodeling. Conversely, suppression of cellular senescence in adipose tissue ameliorates inflammation and systemic metabolic dysfunction, inhibiting the progression of heart failure and the development of diabetes via modulation of insulin signaling. 15,16) In addition to WAT, other types of fat are known to be involved in regulating metabolic homeostasis. Brown adipose tissue (BAT) is highly vascular and abundant in mitochondria that are rich in uncoupling protein-1 (UCP-1), which produce heat by uncoupling the respiratory chain invo...

‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue

“…Particularly abundant in newborns, the BAT is a highly vascularized tissue rich in mitochondria with a high content of uncoupling protein‐1 (UCP‐1), a molecule that produces heat by uncoupling the respiratory chain (Shimizu et al . ). Besides its thermogenic function, BAT contributes to systemic metabolism by virtue of its high‐energy expenditure ratio (Shimizu et al .…”

“…Besides its thermogenic function, BAT contributes to systemic metabolism by virtue of its high‐energy expenditure ratio (Shimizu et al . ). Thus, BAT has basically antagonistic functions to white adipose tissue, i.e.…”

“…This phenomenon is linked to higher risk of cardiometabolic disorders (Shimizu et al . ). The ageing process is associated with an increased accumulation of senescent cells in the adipose tissue, with causative factors being cytokines, metabolic stress, and reduced removal of these cells, which lose the ability to respond efficiently to chemokine signalling (see ‘Stem cell populations’ section).…”

“…Although the underlying mechanism(s) remains to be elucidated, progressive BAT dysfunction or ‘whitening’ is also linked to both ageing and obesity/insulin resistance (Shimizu et al . ).…”

“…Further, excessive lipolysis associated with high SNS activity increases ROS production and activates p53 signalling in the adipose tissue, potentially leading to inflammation of this tissue (Shimizu et al . ). Indeed, although p53 is a transcriptional factor involved in preservation of genomic stability and inhibition of tumorigenesis, it also has some deleterious effects related to age‐associated cardiovascular disorders, e.g.…”