Adipokine dysregulation and adipose tissue inflammation in human obesity

Abstract

Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease and cancer. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins and growth and vasoactive factors, collectively termed adipokines that influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodelling and fibrosis together with an altered secretion of adipokines. This review describes how adipose tissue becomes inflamed in obesity and summarizes key players and molecular mechanisms involved in adipose inflammation.

Leukocytes from obese individuals exhibit an impaired SPM signature

“…The current study explores this possibility by comparing the production of SPMs in peripheral leukocytes isolated from individuals with morbid obesity with those isolated from nonobese controls. The results obtained confirm that leukocytes from obese individuals have an unbalanced formation of SPMs with respect to proinflammatory lipid mediators such as leukotriene (LT) B 4 and prostaglandins (PGs). Moreover, the current study provides new insights into the mechanisms underlying impaired SPM formation in obese leukocytes.…”

“…2G. Importantly, leukocytes from obese individuals showed a significantly reduced ratio of DHA-derived SPM production with respect to the levels of classic inflammatory lipid mediators such as LTB 4 and PGs (Fig. 3A), a finding that was not as evident in the production of EPA-derived SPMs.…”

“…A persistent subclinical state of low-grade inflammation largely dictates the progression of metabolic complications in obese individuals such as insulin resistance, atherosclerosis, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) (1,2). This state of low-grade inflammation associated with obesity involves many components of the classic inflammatory response to pathogens and includes systemic increases in circulating inflammatory cytokines and acute phase proteins (e.g., C-reactive protein), decreases in insulin-sensitizing and anti-inflammatory factors such as adiponectin, and recruitment and subsequent activation of leukocytes into inflamed tissues (3,4). The nature of obesity-induced inflammation, which is known as meta-inflammation, is unique compared with other inflammatory conditions because it is characterized by tonic low-grade activation of the immune system in the absence of active infection and in response to recurrent episodes of overnutrition (5).…”

Could metabolic risk factors contribute to the development of cervical cancer?

“…Some mechanisms have been proposed supporting obesity contribution to risk and progression of cancer. Because of calories excess ingestion, occur some processes like adipose tissue enlargement (hyperplasia and hypertrophy), immune cells in iltration and extracellular matrix remodeling of adipose tissue [18]. Adipocytes and stromal cells from white adipose tissue, cooperatively, modulate important signal pathways involved in initiation and progression of cancer.…”

Macrophage‐Derived microRNA‐155 Increases in Obesity and Influences Adipocyte Metabolism by Targeting Peroxisome Proliferator‐Activated Receptor Gamma

“…Obesity leads to a state of low‐grade chronic inflammation, with the adipose tissue macrophage (ATM) being a key element . Macrophages increase in the adipose tissue of individuals with obesity and are responsible for increased cytokine production and low‐grade inflammation .…”