Tipping the inflammatory balance: inflammasome activation distinguishes metabolically unhealthy from healthy obesity

Abstract

Expansion of adipose tissue mass, predominantly in the visceral depot, strongly associates with the development of metabolic complications that are often observed in obesity. In addition, in obesity, an increased prevalence of nonalcoholic fatty liver disease and reduced cardiorespiratory fitness are observed. However, not all obese individuals develop metabolic abnormalities. To better understand the molecular mechanisms that predispose obese humans to the development of metabolic diseases, comparing the metabolically healthy obese (MHO) vs an unhealthy obese phenotype (MUO) may be of great value. A new study by Esser et al

Macrophages Play a Key Role in the Obesity‐Induced Periodontal Innate Immune Dysfunction via Nucleotide‐Binding Oligomerization Domain‐Like Receptor Protein 3 Pathway

“…Various studies have confirmed that obesity is associated with infiltration of macrophages into: 1) adipose tissue; 2) liver; and 3) skeletal muscle; this in turn leads to local tissue inflammation 15 , 36 , 37 . Adipose tissue inflammation in individuals with obesity is associated with increased activation of NLRP3 inflammasome in macrophages infiltrating adipose tissue, which ultimately leads to insulin resistance 19‐21,38 …”

“…Adipose tissue inflammation in individuals with obesity is associated with increased activation of NLRP3 inflammasome in macrophages infiltrating in visceral adipose tissue, which ultimately leads to insulin resistance 19–21 . Various studies have elucidated that activation of NLRP3 signal pathway in adipose tissue could contribute to insulin resistance of individuals with obesity and inhibition of NLRP3 interleukin (IL)‐1b signaling axis could reduce adipose tissue inflammation and insulin resistance 15 , 22 .…”

Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

“…NLRP3 inflammasome senses lipotoxicity-associated intracellular ceramide increases to initiate caspase-1 cleavage in macrophages and adipose tissue [66]. Importantly, subtypes of metabolically healthy and unhealthy obesity seem to have a different susceptibility to the IL-1β and caspase-1 mediated activation of the NLPR3 inflammasome [67].…”

“…Through the release of lipids or AGEs, adipocyte hypertrophy may cause an activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome [65,66]. NLRP3 inflammasome senses lipotoxicity-associated intracellular ceramide increases to initiate caspase-1 cleavage in macrophages and adipose tissue [66].…”

Metabolically healthy obesity across the life course: epidemiology, determinants, and implications

“…) . In MHO individuals, the excess calories are channeled into insulin‐sensitive subcutaneous adipose tissue, which is capable of expansion; thus, visceral and ectopic adiposity are reduced, macrophage infiltration and raised proinflammatory state are attenuated, insulin sensitivity is preserved, and the individual is protected from development of the MetS …”