Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications

Abstract

Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia). The recruitment and differentiation of adipose precursor cells in the subcutaneous adipose tissue (SAT), rather than merely inflating the cells, would be protective from the obesity-associated metabolic complications. In metabolically unhealthy obesity, the storage capacity of SAT, the largest WAT depot, is limited, and further caloric overload leads to the fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as “lipotoxicity.” Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance (IR). Indeed, overnutrition triggers uncontrolled inflammatory responses in WAT, leading to chronic low-grade inflammation, therefore fostering the progression of IR. This review summarizes the current knowledge on WAT dysfunction in obesity and its associated metabolic abnormalities, such as IR. A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.

2′-Fucosyllactose Supplementation Improves Gut-Brain Signaling and Diet-Induced Obese Phenotype and Changes the Gut Microbiota in High Fat-Fed Mice

“…Obesity pathogenesis involves infiltration of macrophages into expanding adipose tissue and both activated macrophages and hypertrophic adipocytes contribute to local low-grade inflammation in adipose tissue and abnormal hepatic lipid metabolism [66]. Studies have previously demonstrated that animals on HF diets showed chronic inflammation in white adipose tissue and ectopic fat deposition in the liver, which was associated with increased expression of hepatic PPARγ as a transcription factor essential for adipocyte differentiation [67].…”

Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α

“…Obesity-driven changes of the adipose tissue monocytes/macrophages alters the secretion of proinflammatory cytokines which contributes to the progression of inflammation and the development of insulin resistance (19,20). Tumor necrosis factor-α (TNF-α), which is overexpressed in obese humans and rodents, plays a central role in metabolic inflammation and insulin resistance.…”

Dihydropyranocoumarins Exerted Anti-Obesity Activity In Vivo and its Activity Was Enhanced by Nanoparticulation with Polylactic-Co-Glycolic Acid

“…Adipose tissue can expand either by hypertrophy or hyperplasia [19]. On the one hand, hypertrophy of adipocytes can increase hypoxia and mechanical stress to neighboring cells and the extracellular matrix, resulting in decreased adipose tissue function, which contributes to the early onset of metabolic disease, and persistently elevated levels of nutrients in the blood, which cause toxic lipid deposits in other tissues, such as muscle and the liver [20,21]. On the other hand, hyperplastic growth is considered to be a healthy and adaptive mechanism by which to maintain proper vascularization, responses to anti-inflammatory hormone adiponectin, and insulin-sensitizing and other metabolism-modulatory adipokines [20,22].…”